sbobinature nefro_0 - skydrive

127
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

Upload: cristinabizzi

Post on 25-Jul-2015

86 views

Category:

Documents


6 download

TRANSCRIPT

Page 1: sbobinature nefro_0 - SkyDrive

!

! " # # $ % & ' ( ) ) ( * ( + , - # . / & . * ( 0 ( & ( # 1

!"##$%&'(&)*$+#"&,"--%.#"&-%/#0$/$&.$&.$10%/0&20&3$4,%.%50"&2$.&6788(&9.&:"#$,0".$&;&,0-"<"#%&2"..$&.$10%/0&+#$++$=&2"..$&+.02$+&$&#".<%.#"&"/->$&2"&"??,%4%/20:$/#0&<",0(&9&,0#"5.0&2$..$&20"?%+0#0<$&+%/%&2"&-%/+02$,",+0&?,%?,0$#@&0/#$..$##*".$&2$0&,0+?$##0<0&"*#%,0(&!"&->0&+$&/$&4,$5"=&0%&-$&.$&:$##%&.%&+#$++%(&A.-*/0&",5%:$/#0&?%++%/%&-%/#$/$,$&."-*/$&%&-%/#$/$,$&B*".->$&$,,%,$=&?$,&B*$+#%&<0&-%/+05.0%&20&0/#$5,",$&-%/&.0C,0&20&#$+#%&$&B*"/#D".#,%(&E*%/"&?0?F&"&#*##0(&&

2**%1"))"/$3()%1+4546+4551 !GH&

IC%C0/"#*,$&2$.&-%,+%&20&3$4,%.%50"&

Page 2: sbobinature nefro_0 - SkyDrive

!"#$%$&'()*(+,$%$&'-.()()/'01,"2'$*()3(%%")+1*2'$*(),(*"%()

!

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

L1)#5)3!5%!'1''(!:1+&'(!5)&-(*&(!)#'*(51''),(!+4+*7+!1#!5%'(!4(/'(!)4$(*'%#'+G!

45)+$*3"/(*#"%()0"6(,)7"%1#",()%")+1*2'$*(),(*"%()3')1*")6(,0$*"3!+!$+*!0%*/(!%66)%4(!%!5)&$(&)2)(#+!5),+*&)!$%*%4+'*)!+!)#5%7)#)8!

E%!-,("#'*'*(/'"!?!1#!+&%4+!&+4$/)-+3!*(1')#%*)(3!-.+!-)!$+*4+''+!5)!&')4%*+!/%!01#2)(#+!*+#%/+!5)!1#!$%2)+#'+8!"/!7*(&&(!$*(6/+4%!5+//%!-*+%')#)#+4)%!?!-.+!)/!,%/(*+!5+,+!+&&+*+!-(**+''%4+#'+!)#'+*$*+'%'(G!#(#!6%&'%3!)#0%'')3!)/!*)&$+''(!5+//B)#'+*,%//(!5)!*)0+*)4+#'(8!M#2)'1''(3!/%!*+/%2)(#+!'*%!01#2)(#+!*+#%/+!5+/!$%2)+#'+!+!-*+%')#)#+4)%!?!

Page 3: sbobinature nefro_0 - SkyDrive

/)#+%*+!&(/%4+#'+!'*%!W!+!I!47U5E!5)!-*+%')#)#+4)%G!&(''(!%5!W!47U5E!+!&($*%!%!I47U5E!&)!$+*5+!/%!/)#+%*)'>3!$+*!-1)G!

< H+*!,%/(*)!&1$+*)(*)!%!I47U5E!%!$)--(/+!,%*)%2)(#)!5+//%!01#2)(#+!*+#%/+!-(**)&$(#5(#(!%4$)+!,%*)%2)(#)!5+//%!-*+%')#)#+4)%8!

< H+*!,%/(*)!)#0+*)(*)!%!W3W!47U5E3!%!%!7*%#5)!,%*)%2)(#)!5+//%!01#2)(#%/)'>!*+#%/+!-(**)&$(#5(#(!&(/(!4)#)4+!,%*)%2)(#)!5+//%!-*+%')#)#+4)%8!

L1)#5)3!$+*5)'+!5)!:1('+!)4$(*'%#')&&)4+!5)!01#2)(#+!*+#%/+!#(#!&)!%--(4$%7#%#(!#+-+&&%*)%4+#'+!%!,%*)%2)(#)!$*($(*2)(#%/)!5+//%!-*+%')#)#+4)%!-.+3!%#2)3!$1N!*+&'%*+!'*%#:1)//%4+#'+!#+//%!#(*4%8!

E%!-*+%')#)#%3!)#(/'*+3!&$+&&(!,)+#+!5(&%'%!%#-(*%!-(#!1#%!4+'(5)-%!-(/(*)4+'*)-%!$)1''(&'(!,+'1&'%!+!7*(&&(/%#%!-.+!'+#5+!%!&(,*%&')4%*+!/%!-*+%')#)#+4)%!5)!1#!0%''(*+!5)!-)*-%!P3I!47U5E8!X(/')!/%6(*%'(*)3!(*4%)3!1')/)22%#(!4+'(5)-.+!)441#(+#2)4%')-.+!4(/'(!$)F!$*+-)&+!-.+!.%##(!)#!7+#+*+!/)4)')!&1$+*)(*)!$)F!6%&&)!YW3W!47U5EZ8!!

9/'*+!%!:1+&'+!-(#&)5+*%2)(#)3!&(#(!5%!'+#+*+!$*+&+#')!)!&+71+#')!%--(*7)4+#')G!

< 8(*(,()6,(0(*#()%")/"00")-$,6$,(")3(%)6"2'(*#(9)"!/),+//)!$/%&4%')-)!5)!-*+%')#)#%!,%*)%#(!$*($(*2)(#%/4+#'+!%//%!4%&&%!41&-(/%*+!5+/!$%2)+#'+8!H+*'%#'(3!)!6%46)#)!.%##(!,%/(*)!$)F!6%&&)!5)!-*+%')#)#%3!+!171%/4+#'+!7/)!%#2)%#)8!T#!%#2)%#(!-.+!.%!1#%!61(#%!01#2)(#+!*+#%/+!.%!-)*-%!P3;<P3=!47U5E!5)!-*+%')#)#%3!+!:1+&'(!?!+&'*+4%4+#'+!*)/+,%#'+!#+//%!$*%')-%!-/)#)-%3!%#-.+!$+*-.[!(77)7)(*#(!)!*+#)!+&$)%#'%')!5%!$+*&(#+!%#2)%#+!&(#(!1')/)22%')!)#!'*%$)%#'(/(7)%8!!

< 4#:)3(%)6"2'(*#(9)E%!0(*41/%!5)!\(-]-*(0'<^%1/'!-)!$+*4+''+!5)!,%/1'%*+!/%!-/+%*%#-+!5+//%!-*+%')#)#%!)#!*+/%2)(#+!%!4%&&%!-(*$(*+%3!-*+%')#)#%!&)+*)-%!+5!+'>8!

!T#B%/'+*#%'),%!?!/%!X_`_G!

!

!

E%!-'0#"#'*");)?!&'%'%!$*($(&'%!-(4+!$%*%4+'*(!$+*!,%/1'%*+!/%!01#2)(#+!*+#%/+!)#!%/'+*#%'),%!%//%!-*+%')#)#%G!#(#!?!&1$+*)(*+!%//%!-*+%')#)#%!$+*!,%/1'%*+!)!$%2)+#')!-(#!)#&100)-)+#2%!*+#%/+!-*(#)-%!Y%#-.+!%!-%1&%!5+//B)#'+*0+*+#2%!5)!%/'*+!$%'(/(7)+!0*+:1+#')!#+//%!$($(/%2)(#+Z3!4+#'*+!&+46*%!+&&+*+!&1$+*)(*+!%//%!-*+%')#)#%!#+//%!,%/1'%2)(#+!5+/!5%##(!*+#%/+!%-1'(G!%#-(*%3!-(41#:1+3!#(#!?!1')/)22%'%!#+//%!$*%')-%!-/)#)-%!*(1')#%*)%8!

H+*!%5+&&(!%66)%4(!$%*/%'(!5)!-*+%')#)#+4)%3!4%!#(#!%66)%4(!5+''(!#)+#'+!&1//%!-,("#'*'*()-%(","*-(9)a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b+//%!$*%')-%3!:1)#5)3!/%!-/+%*%#-+!5+//%!-*+%')#)#%!?!5)!&-%*&%!1')/)'>8!

Cockcroft-Gault equation •  The Cockcroft-Gault equation allows the creatinine clearance to

be estimated from the serum creatinine in a patient with a stable serum creatinine:

(140 - age) x lean body weight [kg] CCr (mL/min) = —————————————————— Cr [mg/dL] x 72

•  This formula takes into account the increase in creatinine production with increasing weight, and the decline in creatinine production with age. For women, multiplication by 0.85 is required to account for smaller muscle mass compared to men.

•  The equation is not adjusted for body surface area. Therefore to compare normal values, the calculation should be adjusted for body surface area. Normalization for body surface increases the accuracy of this equation, particularly among those with decreased renal function.

MDRD Equation

• www.kidney.org/professionals/KLS/gfr_calculator.cfm • nephron.com/mdrd/default.html

NKF's KDOQI clinical practice guidelines recommend the Modification of Diet in Renal Disease

(MDRD) Study equation to estimate GFR

GFR, in mL/min per 1.73 m2 = 175 x SCr (exp[-1.154]) X

Age (exp[-0.203]) X (0.742 if female) x (1.21 if black)

The commonly utilized estimation equations are less accurate in individuals with normal GFR, children, elderly patients, specific ethnic groups, pregnant

women, and those with unusual muscle mass, body habitus, and weight.

Page 4: sbobinature nefro_0 - SkyDrive

H1*'*($$(3!$+*N3!#+%#-.+!/%!-*+%')#)#%!?!1#!$%*%4+'*(!%''+#5)6)/+!)#!-%&(!5)!)#&100)-)+#2%!*+#%/+!%-1'%3!$()-.[!/%!&1%!-(#-+#'*%2)(#+!5+,+!%#5%*+!%!$/%'+%1!#+/!&%#71+!%00)#-.[!1#%!&1%!4)&1*%!&)%!%''+#5)6)/+G!)#!"`M!/B+/+,%2)(#+!5+//%!-*+%')#)#%!&)!(&&+*,+*+66+!&(/(!5($(!:1%/-.+!'+4$(8!!

<'*3,$/')=(+,$%$&'-.()

!

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`\8!E%!4%77)(*!$%*'+!5+)!$%2)+#')!-(#!$%'(/(7)+!*+#%/)!-*(#)-.+3!$+*N3!%/!4(4+#'(!5+//%!$*+&+#'%2)(#+!#(#!.%##(!%#-(*%!1#%!&'1%2)(#+!5)!)#&100)-)+#2%!*+#%/+!-*(#)-%!4%3!$+*!+&+4$)(3!&(/(!1#%!$*('+)#1*)%!+!:1)#5)!5(66)%4(!+&&+*+!#()!-(#!)/!#(&'*(!)#'+*,+#'(!%!$*+&+*,%*+!/%!01#2)(#%/)'>!*+#%/+!+3!$(&&)6)/4+#'+3!%!*)&(/,+*+!(!$+*!/(!4+#(!*%//+#'%*+3!/%!$*(7*+&&)(#+!5+//%!4%/%'')%8!

T71%/4+#'+3!$()3!/+!-(#5)2)(#)!5)!%/'+*%2)(#+!5+//%!01#2)(#+!1*)#%*)%!$(&&(#(!%--(4$%7#%*&)!%//%!%/'+*%2)(#+!5+/!&+5)4+#'(!Y4)-*(+4%'1*)%3!/+1-(-)'1*)%3!$*('+)#1*)%cZ8!L1)#5)3!)#!&(&'%#2%3!)!0+#(4+#)!&-*)'')!)#!*(&&(!$(&&(#(!+&)&'+*+!&)%!)#!0(*4%!)&(/%'%3!&)%!-(46)#%')!'*%!/(*(3!&)%!%&&(-)%')!%//+!-(#5)2)(#)!5)!%/'+*%2)(#+!5+//%!+1*2'$*(),(*"%(3!&-*)''+!)#!#+*(8!"#(/'*+3!/+!-(#5)2)(#)!5)!%/'+*%'%!01#2)(#+!$(&&(#(!$*+&+#'%*&)!)#!%&&+#2%!5+)!0+#(4+#)!&-*)'')!)#!*(&&(8!

>9 !,$#('*1,'")

E%!$*('+)#1*)%!?!/%!&)#5*(4+!#+0*(/(7)-%!$)F!0*+:1+#'+!)#!%&&(/1'(3!%#-.+!)#5)$+#5+#'+4+#'+!5%//+!-(#5)2)(#)!-.+!-(4$(*'%#(!1#%!*)512)(#+!5+//%!01#2)(#%/)'>!*+#%/+8!E%!$*('+)#1*)%!?!/%!6(,3'#")3')6,$#('*()*(%%()1,'*(9)9*%3!'1'')!#()!$+*5)%4(!:1(')5)%#%4+#'+!1#%!-+*'%!:1%#')'>!5)!$*('+)#+3!#(#!&1$+*)(*+!%!>?@)/&)*(%%()AB)$,()+!:1+&'(!?!0)&)(/(7)-(8!d!)4$(*'%#'+!-.+!/%!4)&1*%!5+//%!$*('+)#1*)%!&)%!(''+#1'%!4+5)%#'+!/%!*%--(/'%!5+//+!1*)#+!#+//+!IQ!(*+3!$()-.[!/B+&%4+!5+//+!1*)#+!&'%#5%*5!?!%&&(/1'%4+#'+!)#%''+#5)6)/+3!$()-.[!&'*+''%4+#'+!5)$+#5+#'+!5%//%!-(#-+#'*%2)(#+!5+//+!1*)#+!5)!:1+//%!$%*')-(/%*+!4)#2)(#+8!H+*!+&+4$)(3!&+!5+'+*4)#%&&)4(!/%!$*('+)#1*)%!&1!1#!-%4$)(#+!5)!1*)#+!*%--(/'+!%/!*)&,+7/)(3!:1%#5(!/B1*)#%!?!$)F!-(#-+#'*%'%3!0)#)*+44(!$+*!&1$$(**+!1#%!

Sindromi nefrologiche

Sedimento negativo Assenza di proteine

Microalbuminuria Proteinuria Ematuria

Sindrome Nefrosica Sindrome Nefritica

Insufficienza renale acuta

Insufficienza renale cronica Funzione normale

Insufficienza renale rapidamente progressiva

Page 5: sbobinature nefro_0 - SkyDrive

$*('+)#1*)%!-.+!#(#!+&)&'+!&+4$/)-+4+#'+!$+*-.[!)/!#(&'*(!-%4$)(#+!?!4(/'(!-(#-+#'*%'(8!!

"!WSP!47!5)!$*('+)#+!-.+!$+*5)%4(!-(#!/+!1*)#+!&(#(!$+*!/(!$)F!6,$#('*()#1C1%",'9)E+!$*('+)#+!5+/!&%#71+!Y"%C1/'*"Z!#(#!5+,(#(!-(4$%*)*+!#+//B1*)#%8!E%!6%**)+*%!5)!0)/'*%2)(#+!7/(4+*1/%*+!?!&'*1''1*%'%!)#!4(5(!'%/+!5%!#(#!/%&-)%*!$%&&%*+!#+/!0)/'*%'(!$*('+)#+!5)!5)4+#&)(#)!&1$+*)(*)!%!WSP!]_%8!E+!$*('+)#+!5)!=P<WSP!]_%!$*('+66+*(!'*)#($,'"!$%&&%*+!&+!$*+#5)%4(!)#!-(#&)5+*%2)(#+!+&-/1&),%4+#'+!/+!5)4+#&)(#)!5+)!$(*)!5)!0)/'*%2)(#+G!/%!4+46*%#%!5)!0)/'*%2)(#+!?!$+*N!-%*)-%!#+7%'),%4+#'+!7*%2)+!%5!+/+4+#')!$*('+)-)!+!$*('+(7/)-%#)-)3!$+*'%#'(!/B%/614)#%!,)+#+!*+&$)#'%!)#!:1%#'(!%!&1%!,(/'%!-%*)-%!#+7%'),%4+#'+8!H+*'%#'(3!&+!'1''(!01#2)(#%!#+//%!#(*4%3!#(#!5(,*+66+!,+*)0)-%*&)!/%!$+*5)'%!5)!%/614)#%!#+//+!1*)#+8!9*%3!*+%/)&')-%4+#'+3!&)!-(#&)5+*%!-(4+!/)4)'+!&1$+*)(*+!5+//%!$+*5)'%!5)!%/614)#%!#+//+!1*)#+!)/!,%/(*+!&(7/)%!)#0+*)(*+!$+*!/%!4)-*(%/614)#1*)%G!D@)/&E)AB)$,(9)F1'*3'G)#,")D@)/&)()D@@)/&)*(%%()AB)$,()0')6",%")3')/'-,$"%C1/'*1,'"9)H%#,()')D@@)/&EAB)$,()&)!$%*/%!5)!6,$#('*1,'"9)L1+&')!,%/(*)!.%##(!1#!&)7#)0)-%'(!$*%')-(G!5%!KPP!47UIQ!(*+!/B%/614)#%!5),+#'%!)5+#')0)-%6)/+!%#-.+!%//B+&%4+!&'%#5%*5!5+//+!1*)#+3!4+#'*+!%/!5)!&(''(!5+)!KPP!47UIQ!(*+!?!+,)5+#2)%6)/+!&(/(!*)-.)+5+#5(!1#!5(&%77)(!&$+-)0)-(!5+//%!4)-*(%/614)#1*)%8!!

977)!&%$$)%4(!-.+!)/!$*)#-)$%/+!4%*]+*!5)!5%##(!*+#%/+!#(#!?!'%#'(!/%!$*+&+#2%!5)!$*('+)#+!)#!&+#&(!/%'(!#+//+!1*)#+3!6+#&e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

T#!%/'*(!)4$(*'%#'+!,%/(*+!&(7/)%!5%!'+#+*+!$*+&+#'+!?!:1+//(!5+)!DG?)&EAB)$,(G)-.()3(+'*'0-()%")0'*3,$/()*(+,$0'-")I,"66$,#"#$)"%%")016(,+'-'()-$,6$,("J9))

V)$)!5)!$*('+)#1*)%!

M66)%4(!5+0)#)'(!/%!$*('+)#1*)%!&1/!$)%#(!:1%#')'%'),(8!M#-.+!/B%&$+''(!:1%/)'%'),(3!$+*N3!?!4(/'(!)4$(*'%#'+8!O)!*)-(#(&-(#(!5),+*&)!')$)!5)!$*('+)#1*)%!%!&+-(#5%!5+/!4+--%#)&4(!$%'(7+#+')-(!+3!-(#&+71+#'+4+#'+3!5+//%!#%'1*%!5+//+!$*('+)#+!-.+!-(4$%)(#(!#+//+!1*)#+8!

%8 H*('+)#1*)%!^/(4+*1/%*+!

_+*),%!5%!1#B%/'+*%2)(#+!5+//%!4+46*%#%!5)!0)/'*%2)(#+!7/(4+*1/%*+!+5!?!:1)#5)!)#5)-+!5)!$%'(/(7)%!7/(4+*1/%*+8!"/!4+--%#)&4(!$*+,+5+!/B)$+*0)/'*%2)(#+!5)!4%-*(4(/+-(/+!Y&($*%''1''(!%/614)#%Z!%''*%,+*&(!1#B%/'+*%'%!4+46*%#%!5)!0)/'*%2)(#+8!

Page 6: sbobinature nefro_0 - SkyDrive

!

68 H*('+)#1*)%!5%!(,+*0/(f!

E+!$*('+)#+!%!6%&&(!$+&(!4(/+-(/%*+!&(#(!)#!7*%5(!5)!%''*%,+*&%*+!)#!1#%!-+*'%!4)&1*%!/%!4+46*%#%!5)!0)/'*%2)(#+!+!5)!$%&&%*+!#+/!0)/'*%'(!7/(4+*1/%*+8!"#!&+71)'(3!+&&+!&(#(!5+4(/)'+!5%!$*('+%&)!+!$+$')5%&)!5+//%!4+46*%#%!'161/%*+!+!*)%&&(*6)'+!5%)!-%**)+*&!5+//B+$)'+/)(!'161/%*+8!L1%#5(!/%!:1('%!5)!:1+&'+!$*('+)#+!%!6%&&(!$+&(!4(/+-(/%*+!%14+#'%!+--+&&),%4+#'+3!%14+#'%!171%/4+#'+!/%!:1%#')'>!5)!'%/)!$*('+)#+!#+/!0)/'*%'(!7/(4+*1/%*+!+!/%!-%$%-)'>!5)!*)%&&(*6)4+#'(!'161/%*+!YV4%gZ!,)+#+!&1$+*%'%3!$+*'%#'(!'%/)!$*('+)#+!-(4$%)(#(!#+//+!1*)#+8!EB+&+4$)(!$)F!#('(!?!&)-1*%4+#'+!:1+//(!5+//%!6,$#('*1,'")3')K(*-(LM$*(0!)#!-(*&(!5)!7%44($%')%!4(#(-/(#%/+8!!

-8 H*('+)#1*)%!'161/%*+!

H%'(/(7)+!'161/()#'+*&')2)%/)!$(&&(#(!5+'+*4)#%*+!5%##(!'161/%*+!+!-(#&+71+#'+!5+0)-)'!5+)!4+--%#)&4)!5)!*)%&&(*6)4+#'(!5+//+!$*('+)#+!-.+!0)/'*%#(!#+//+!1*)#+8!O)!%,*>!%14+#'(!5+)!/),+//)!1*)#%*)!5)!%/614)#%!+!-(4$%*)*%##(!#+//+!1*)#+!%#-.+!$*('+)#+!5)!(*)7)#+!'161/%*+!Y+&G!!I<4)-*(7/(61/)#%Z8!

!

`%$$(*'(!$*('+)#1*)%U-*+%')#)#1*)%!

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

Cause Renal Manifestation Clinical Presentation Laboratory/Imaging

Diabetes mellitus type 1/type 2 Ranging from microalbuminuria to nephrotic range proteinuria; most common etiology of end-stage renal disease in the US

Polyuria, polydipsia, nocturia, weight loss

Fasting plasma glucose 126 mg/dL (7.0 mmol/L). Increased HbA1c.

Hypertension Microalbuminuria Often asymptomatic (excluding hypertensive crisis)!

Other possible signs of hypertensive injury

Crescentic glomerulonephritis *Proteinuria with an active urinary sediment and decreased GFR

Sign or symptoms of uremia Increased creatinine and BUN levels. Hypertension. ANCA and anti-GBM antibodies

Multiple myeloma SCr is increased in 50% of patients15; urine protein is not detected on urine dipstick; sulfosalicylic acid test and UPCR detect proteinuria

Pallor, radiculopathy, peripheral neuropathy, bone pain in the back or chest is present in 60% of patients27

Monoclonal protein in serum and/or protein electrophoresis, lytic lesions and fractures on x-ray, hypercalcemia

Light chain deposition disease Most commonly associated with multiple myeloma; in rare cases it is occurs with lymphoma

Related to renal, cardiac, or hepatic involvement

Tissue deposition of kappa light chains, urinary light chain excretion

Primary amyloidosis Nephrotic syndrome with or without renal insufficiency

Peripheral neuropathy, macroglossia, hepatomegaly

Amyloid deposition on biopsy; evidence of a clonal plasma cell proliferative disorder

HIV nephropathy Nephrotic syndrome, slowly progressive renal dysfunction

More common in African-American patients; edema

HIV positive

Immunoglobulin A nephropathy From urine abnormalities to nephritic syndrome Hematuria Renal immunoglobulin A deposition; active urine sediment

Minimal change disease, FSGS membranous glomerulonephritis

Nephrotic syndrome Edema, anasarca, foamy urine Hypercholesterinemia, hypoalbuminemia, proteinuria; diagnostic renal biopsy findings

Streptococcal glomerulonephritis Ranging from microscopic hematuria to acute nephritic syndrome

Recurrent episodes of hematuria Kidney biopsy shows proliferative glomerulonephritis

Other forms of glomerulonephritis, infectious or systemic diseases

Proteinuria with or without an active urinary sediment (red blood cell casts, dysmorphic erythrocytes)!

Depending on underlying disease ANA, complement C3 and C4, VDRL, hepatitis serology, cryoglobulins

Common Causes of Glomerular Proteinuria

Page 7: sbobinature nefro_0 - SkyDrive

7"%$,()N)@GA).")1*")6,$#('*1,'"9)!"/!,%/(*+!5+/!*%$$(*'(!$*('+)#1*)%U-*+%')#)#1*)%!?!)#!*%$$(*'(!/)#+%*+!-(#!/%!$*('+)#1*)%!5+//+!IQ!(*+!#+//B%51/'(8!

!

H*('+)#1*)%!(*'(&'%')-%!+!'*%#&)+#'+!

E%!$*('+)#1*)%!'*%#&)+#'+!?!$+*!5+0)#)2)(#+!1#%!$*('+)#1*)%!+$)&(5)-%!-.+!#(#!&)!*)$+'+8!H1N!-%$)'%*+!)#!$%*')-(/%*)!&)'1%2)(#)!5)!&(00+*+#2%!*+#%/+G!1#%!0+66*+!4(/'(!%/'%3!$+*!+&+4$)(3!$1N!)#51**+!$*('+)#1*)%8!!

h)-+,+*&%3!+&)&'(#(!&(77+'')!-(#!$*('+)#1*)%!-*(#)-%!5)!/)+,+!+#')'>!-.+!$+77)(*%!4(/'(!)#!-%&(!5)!&,(/7)4+#'(!5)!%''),)'>!0)&)-%G!+*%!-(#&)5+*%'%!1#%!-(#5)2)(#+!6+#)7#%3!-(41#+!%!5),+*&)!*%7%22)!7)(,%#)!+!6%46)#)3!#(#!$*+(--1$%#'+8!E+!-(&+!#(#!&'%##(!-(&e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

^+&')(#+!5+//%!$*('+)#1*)%!

_)!0*(#'+!%/!$%2)+#'+!-(#!$*('+)#1*)%!5(66)%4(!41(,+*-)!-(&eG!

< O+!?!1#%!$*('+)#1*)%!7*%,+3!5(66)%4(!&'%6)/)*+!&+!&)%!)&(/%'%!(!&+!&)%!)#,+-+!)&(/%'%!%!4)-*(+4%'1*)%8!"#!+#'*%46)!)!-%&)3!-(41#:1+3!)/!$%2)+#'+!5+,+!+&&+*+!)#5)*)22%'(!)44+5)%'%4+#'+!%5!1#(!&$+-)%/)&'%8!

< O+!/%!$*('+)#1*)%!#(#!?!$%*')-(/%*4+#'+!7*%,+3!5(66)%4(!+00+''1%*+!)/!5(&%77)(!5+//%!4)-*(%/614)#1*)%!$+*!-%$)*+!&+!:1+&'%!$*('+)#1*)%!?!5)!(*)7)#+!7/(4+*1/%*+!YiPR!5+)!-%&)Z!+!'+#+*/%!-(#'*(//%'%!#+/!'+4$(8!9,,)%4+#'+3!$()3!5(66)%4(!&'%6)/)*#+!/%!-%1&%8!!

b(#!?!0%-)/+!&'%6)/)*+!/%!-%1&%!5)!1#%!$*('+)#1*)%!)&(/%'%3!&($*%''1''(!&+!/)+,+8!O$+&&(!)!$%2)+#')!.%##(!1#%!&'(*)%!-/)#)-%!&177+&'),%!5)!$%'(/(7)+!-.+!$('*+66+*(!%,+*!-%1&%'(!1#!5%##(3!*)7(*(&%4+#'+!$%&&%'+!)#(&&+*,%'+8!"/!5%##(!*+#%/+!-%1&%!/%!$+*5)'%!5)!%/-1#)!#+0*(#)8!"!#+0*(#)!*)4%#+#')!Y&+-(#5(!/%!'+(*)%!5+/!#+0*(#+!)#'%''(Z!-(4)#-)%#(!%//(*%!%5!)$+*<01#2)(#%*+!+5!)$+*0)/'*%*+!Y-(#!-(#&+71+#'+!$*('+)#1*)%!+5!)$+*'+#&)(#+Z3!&(66%*-%#5(&)!5)!1#!-%*)-(!7+&')(#%/+!+--+&&),(!+!%#5%#5(!$*(7*+&&),%4+#'+!)#-(#'*(!%!5)&01#2)(#+8!L1+&'(!&+4$/)-+!&-.+4%!?!%//%!6%&+!5)!1#%!0+''%!)4$(*'%#')&&)4%!5)!$%'(/(7)+!*+#%/)!-*(#)-.+8!

!

O'-,$(/"#1,'")()/"-,$(/"#1,'")

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

Page 8: sbobinature nefro_0 - SkyDrive

<'*3,$/()*(+,'#'-")"-1#")

`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

< a4%'1*)%!4%-*(&-($)-%!YKPRZ!-(#!1*)#+!%!/%,%'1*%!5)!-%*#+!< X)-*(+4%'1*)%!YWPPRZ!< H*('+)#1*)%!&16#+0*(&)-%!YWPPRZ!< `)512)(#+!%-1'%!5+//%!01#2)(#+!*+#%/+!-(#!*)'+#2)(#+!)5*(&%/)#%!+!&,)/1$$(!5)!

+5+4%8!EB+5+4%!?!5%!(/)71*)%3!:1)#5)!5%!)$+*,(/+4)%3!+!7+#+*%/4+#'+!?!/)4)'%'(!%/!,(/'(!+5!?!5)!/)+,+!+#')'>8!

< _(/(*+!/(46%*+!< a/+,%2)(#+!-*+%')#)#+4)%!4(5+&'%!YjI!47U5EZ!< `%*%4+#'+3!+#-+0%/($%')%!)$+*'+#&),%!

"/!:1%5*(!-/%&&)-(!-.+!&)!$*+&+#'%,%!#+)!6%46)#)!&)!*+#5+,%!+,)5+#'+!-(#!7/)!+5+4)!+!/+!1*)#+!*(&&+8!!

<'*3,$/()*(+,$0'-")

O)!5+0)#)&-+!-(4+!/%!6(,3'#")3')6'P)3')DG?)&)3')6,$#('*()*(%%()1,'*()3(%%()AB)$,()I*$,/"%'22"#")6(,)016(,+'-'()-$,6$,("J)"--$/6"&*"#")3"Q))

< 43(/"))< R6$"%C1/'*(/'")< R6(,%'6'3(/'")()%'6'31,'")< S1/(*#"#")010-(##'C'%'#:)"%%()'*+(2'$*')< <#"#$)3')'6(,-$"&1%"C'%'#:)

E%!$*('+)#1*)%!%/!5)!&($*%!5+)!K3S!7!5+0)#)&-+!/%!&)#5*(4+!#+0*(&)-%!%#-.+!&+!'1'')!7/)!%/'*)!&+7#)!&(#(!%&&+#')8!!a--(!1#!+/+#-(!5+//+!$*)#-)$%/)!%/'+*%2)(#)!5+/!$*(0)/(!$*(')5)-(!&)+*)-(!#+/!$%2)+#'+!-(#!&)#5*(4+!#+0*(&)-%G!

!

!

!

!

!

!

!

EB(3(/"!&)!&,)/1$$%!:1%#5(!/B%/614)#%!$/%&4%')-%!&-+#5+!&(''(!%)!I3S!7U5E3!$()-.[!/%!$*+&&)(#+!(#-(')-%!$/%&4%')-%!&)!*)51-+!%!-%1&%!5+//%!$+*5)'%!5)!$*('+)#+!-(#!/+!1*)#+!+!$%*%//+/%4+#'+!/B%''),%2)(#+!5+)!&)&'+4)!5)!-(4$+#&(!-%1&%!*)'+#2)(#+!)5*(&%/)#%!0)#%/)22%'%!%/!4%#'+#)4+#'(!5+//%!,(/+4)%8!O)--(4+!$+*N!)/!$/%&4%!.%!*)5(''%!$*+&&)(#+!

< albumina < !1 globuline > !2 e " globuline Immunoglobuline < IgG +/- > IgA, IgM, IgE < proteine di trasporto dei metalli (Fe, Cu, Zn) < eritropoietina

< transferrina < transcortina < TGB, < T4 < vitamin D-binding protein Complemento < fattore B < C3, C4bp < C1q, C2, C8, Ci < C4 >/- C1s, C4, inibitore di C1

Proteine plasmatiche nella sindrome nefrosica

< albumina < !1 globuline > !2 e " globuline Immunoglobuline < IgG +/- > IgA, IgM, IgE < proteine di trasporto dei metalli (Fe, Cu, Zn) < eritropoietina

< transferrina < transcortina < TGB, < T4 < vitamin D-binding protein Complemento < fattore B < C3, C4bp < C1q, C2, C8, Ci < C4 >/- C1s, C4, inibitore di C1

Proteine plasmatiche nella sindrome nefrosica

Page 9: sbobinature nefro_0 - SkyDrive

(#-(')-%3!/B%-:1%!'*%''+#1'%!7*%2)+!%//%!*)'+#2)(#+!&(5)-%!&)!5)&'*)61)&-+!%//B)#'+*&')2)(!+!#(#!,)+#+!'*%''+#1'%!#+/!'(**+#'+!-)*-(/%'(*)(8!O)!'*%''%!5)!1#!+5+4%!4(/'(!7*%,+!Y+5+4%!5+7/)!%*')3!%&-)'+3!$+*)-%*5)'+3!+5+4%!$(/4(#%*+Z!+!&)!$(&&(#(!&,)/1$$%*+!,+*)!+!$*($*)!&'%')!%#%&%*-%')-)!+!)/!4(#)'(*%77)(!5+//%!'+*%$)%!&)!+00+''1%!$+&%#5(!)/!$%2)+#'+8!EB+5+4%!#+0*(&)-(!.%!51+!-(4$(#+#')!)#'+*-(##+&&+G!/%!-(4$(#+#'+!1*3(,+'%%'*&!+!/%!-(4$(#+#'+!$7(,+%$T8!L1+&'+!51+!-(4$(#+#')!$(&&(#(!$*+&+#'%*&)!#+//(!&'+&&(!$%2)+#'+!4%!$(&&(#(!%#-.+!$*+,%/+*+!/B1#%!&1//B%/'*%8!H+*!+&+4$)(3!#+)!$%2)+#')!)#!-1)!-B?!1#B)4$(#+#'+!%''),%2)(#+!5+)!&)&'+4)!5)!-(4$+#&(!-(4+!-(#&+71+#2%!6,'/'#'7"!5+//%!$%'(/(7)%3!&)!.%!1#%!&)'1%2)(#+!5)!'6(,7$%(/'"!-.+!$*+,%/+!&1//%!*)512)(#+!5+//%!$*+&&)(#+!(#-(')-%3!+!$+*'%#'(!:1+&')!$%2)+#')!.%##(!1#!+5+4%!5%!(,+*0/(f!$*+,%/+#'+4+#'+8!"#!:1+&')!$%2)+#')!/B1&(!5+)!5)1*+')-)!#(#!-(4$(*'%!7*(&&)!$*(6/+4)8!b+)!$%2)+#')!-(#!$*+,%/+#2%!5+//%!*)512)(#+!5+//%!$*+&&)(#+!(#-(')-%3!/%!&)'1%2)(#+!?!)#,+-+!:1+//%!5)!)$(,(/+4)%3!+!/B%''),%2)(#+!5+)!&)&'+4)!5)!-(4$+#&(!&(5)(<*)'+#'),)!?!1#%!-$*0(&1(*2")3(%%51*3(,+'%%'*&G!%//(*%3!)!5)1*+')-)!5+,(#(!+&&+*+!)4$)+7%')!-(#!-%1'+/%!+!$*+,)%!+&$%#&)(#+!$/%&4%')-%!($$(*'1#%8!L1+&')!$%2)+#')!.%##(!6%&&)!/),+//)!5)!MbH8)

!

`)&-.)!5+//B+5+4%!5%!1#5+*0)//)#7G!

< O.(-]!)$(,(/+4)-(!< V%-.)-%*5)%!< "$('+#&)(#+!7*%,+!< "`M!Y&$+-)%/4+#'+!&+!&)!%&&14(#(!kMbOZ!

b+//B+5+4%!5%!(,+*0/(f3!)#,+-+3!)/!*)&-.)(!$)F!7*(&&(!?!/B+5+4%!$(/4(#%*+!%-1'(3!&($*%''1''(!&+!)!$%2)+#')!,+#7(#(!'*%''%')!+**(#+%4+#'+!-(#!%/614)#%!(!$/%&4%!+g$%#5+*&3!-(4+!&+!0(&&+*(!)$(,(/+4)-)8!L1+&'(!'*%''%4+#'(!5+'+*4)#%!1#!1/'+*)(*+!)#-*+4+#'(!5+//%!,(/+4)%!+5!+5+4%!$(/4(#%*+!%-1'(!#(#!-%*5)(7+#(8!!

!EB)$+*/)$)5+4)%!&)!&,)/1$$%!$+*-.[3!(/'*+!%//B%/614)#%3!&)!$+*5(#(!$*('+)#+!/+7%#')!)!/)$)5)!$/%&4%')-)G!-(/+&'+*(/(!+!'*)7/)-+*)5)!&)!'*(,%#(!:1)#5)!/)6+*)!#+/!&%#71+8!"/!0+7%'(3!%//(*%3!'+#5+!%5!%14+#'%*+!/%!&)#'+&)!5)!%$(/)$($*('+)#+!5)!')$(!hE_E!+!*%//+#'%!)/!-%'%6(/)&4(!5+//+!E_E3!5+'+*4)#%#5(!1#!%&&+''(!6,$"#(,$&(*'-$8!M#-.+!/%!&)#'+&)!5+)!0%''(*)!5+//%!

Diagnosi •  I pazienti con overflow (aumentato volume intravascolare) sono più spesso

quelli con funzione renale ridotta (<50% del normale), una concentrazione plasmatica di albumina > 2 g/dl ed ipertensione. Sono più spesso affetti da GN membranosa o glomerulosclerosi focale e segmentale.

•  I pazienti con componente da underfilling (ridotto volume plasmatico) sono quelli con funzione renale normale o di poco ridotta, ipoalbuminemia grave (spesso <1 g/dl) e a rapida insorgenza Sono più spesso affetti da malattia a lesioni minime.

Infiltrato infiammatorio tubulo-interstiziale

Secrezione di angiotensina II

Riduzione del filtrato

glomerulare

Aumentato riassorbimento

di sodio

Ritenzione primitiva di sodio

Perdita di albumina con le urine

Ipoalbuminemia Ridotta

pressione oncotica Soppressione della

sintesi epatica di albumina

Edema Ritenzione di sodio

Page 10: sbobinature nefro_0 - SkyDrive

-(%71/%2)(#+!%14+#'%3!4+#'*+!,+#7(#(!$+*&)!-(#!/+!1*)#+!)!0%''(*)!)#)6)'(*)!0)&)(/(7)-)!5+//%!-%&-%'%!-(%71/%'),%3!-(#!-(#&+71+#'+!&'%'(!6,$#,$/C$#'-$8

!

E%!$+*5)'%!5)!"7^!+!5)!0%''(*)!5+/!-(4$/+4+#'(!-%1&%!)#,+-+!1#%!/"&&'$,()010-(##'C'%'#:)"%%()'*+(2'$*'G)0$6,"##1##$)3")-$--.')-"601%"#'9))

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

"#(/'*+3!&)!.%!/%!$+*5)'%!5)!$*('+)#+!-.+!/+7%#(!5),+*&)!')$)!5)!(*4(#+!Y$+*!+&+4$)(3!(*4(#)!')*()5+)Z3!(/)7(+/+4+#')3!,)'%4)#+3!+",/"-'9))

H(&&)6)/)!-%1&+!5)!&)#5*(4+!#+0*(&)-%G!

!

!

Sindrome Nefrosica Proteinuria > 3.5 g nelle 24 ore, accompagnata da edema,

ipoalbuminemia (<2,5 g/dl), iperlipidemia and lipiduria.

Proteinuria

Ipercoagulabilità

Trombosi Embolia Polmonare

Perdita di inibitori della coagulazione

Sintesi epatica di fattori della coagulazione e piastrine

Perdita di IgG e di complemento

Infezioni

Edema

Instabilità cardiovascolare

Perdita della globulina legante il colecalciferolo

Iperparatiroidismo secondario

Osteomalacia Osteite Fibrosa

Sintesi VLDL Catabolismo LDL

Perdita fattori regolatori

Aterosclerosi

Sindrome nefrosica - cause Glomerulonefriti primitive

bambini < 60 anni > 60 anni MCD 76% 20% 20% GSF 8% 15% 2% GN membranosa 7% 40% 39% MPGN 4% 7% -- altre 5% 18% 39% Nefropatia diabetica Amiloidosi renale Cause rare glomerulopatia fibrillare malattia da deposito di catene leggere pre-eclampsia forme post-infettive e para-infettive neoplasie (in genere MCD) malattie sistemiche (LES, altre

collagenopatie, vasculiti) GN eredofamiliari (sindrome di Alport, nail-patella sindrome) Reazioni allergiche (farmaci, veleni, punture di insetti, antigeni inalati)

Page 11: sbobinature nefro_0 - SkyDrive

V+*%$)%!

"!51+!-%$)&%/5)!5+//%!'+*%$)%!5)!(7#)!0(*4%!5)!$*('+)#1*)%!&(#(G!

< U(0#,'2'$*()3(%%5"66$,#$)0$3'-$)9*4%)!?!$*(,%'(!-.+!1#!+--+&&(!#+//B%$$(*'(!&(5)-(!.%!1#!)4$(*'%#')&&)4(!+00+''(!$+77)(*%'),(!&1//%!$*('+)#1*)%8!"/!*+#+!5+//B+&&+*+!14%#(!&)!?!%5%''%'(!#+/!-(*&(!5+//B+,(/12)(#+!$+*!*)1&-)*+!%!'*%''+#+*+!:1+//+!$)--(/+!+!$*+2)(&+!:1%#')'>!5)!&(5)(!$*+&+#')!&1//%!'+**%0+*4%G!(77)3!$+*N3!/%!#(&'*%!5)+'%!'+#5+!%!0(*#)*+!%/!#(&'*(!(*7%#)&4(!1#!%$$(*'(!5)!&(5)(!+&%7+*%'(!+!:1+&'(!-%1&%!&(00+*+#2%!*+#%/+8!E%!*)512)(#+!5+//B%$$(*'(!&(5)-(!#+)!$%2)+#')!-(#!(,+*0/(f!?!1')/+!%#-.+!$+*!/)4)'%*+!/B+&$%#&)(#+!,(/+4)-%8!!

< S;4LR)$)<",#"*')L1+&')!0%*4%-)!.%##(!-(4$/+'%4+#'+!*),(/12)(#%'(!/%!$*(7#(&)!5+//+!$%'(/(7)+!*+#%/)8!H*)4%!5+/!/(*(!%,,+#'(3!1#!$%2)+#'+!-(#!$*('+)#1*)%!+*%!5+&')#%'(!%//%!4(*'+!$+*!+,+#')!-%*5)(,%&-(/%*)!(!%//%!5)%/)&)8!O(#(!0%*4%-)!-.+!%7)&-(#(!5)4)#1+#5(!)!/),+//)!-)*-(/%#')!5)!MV""!YM\a<"Z!(!,)+'%#5(!)/!/+7%4+!5+//BMV""!%/!&1(!*+-+''(*+3!+!$+*'%#'(!)#51-(#(!1#%!,%&(5)/%'%2)(#+!5+//B",#(,'$%")(++(,(*#(3!*)51-+#5(!-(&e!/B+--+&&),%!$*+&&)(#+!)5*(&'%')-%!#+)!-%$)//%*)!7/(4+*1/%*)3!-)(?!/B)$+*'+#&)(#+!7/(4+*1/%*+8!!^/)!M\a<"!+!)!&%*'%#)!*)51-(#(!)#!4(5(!%#-.+!6*)//%#'+!/%!$*('+)#1*)%3!4%!5+,(#(!+&&+*+!1&%')!-(#!%--(*'+22%8!O(#(!&'%')!'*%5)2)(#%/4+#'+!-(#&)5+*%')!0%*4%-)!4(/'(!&)-1*)3!4%!.%##(!51+!)4$(*'%#')!+00+'')!-(//%'+*%/)G!

< "$+*]%/)+4)%!Y$+*!*)512)(#+!5+)!/),+//)!5)!%/5(&'+*(#+Z!< "#&100)-)+#2%!*+#%/+!%-1'%!

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a<"!(!)/!&%*'%#(!#+/!-%&(!&)!$*+&+#')!1#%!&"0#,$(*#(,'#()"-1#"G!)#!:1+&'(!-%&(!)/!&)&'+4%!*+#)#%<%#7)('+#&)#%!5+,+!%''),%*&)!$+*!-(4$+#&%*+!/%!$+*5)'%!,(/+4)-%!-%1&%'%!5%/!,(4)'(!+U(!5%//%!5)%**+%3!+!1&%*+!1#!0%*4%-(!-.+!6/(--.)!:1+&'(!&)&'+4%!&)7#)0)-%!*)&-.)%*+!D!)#!*%$$(*'(!%//%!-(4(*6)5)'>!-.+!.%!*+&(!#+-+&&%*)(!)/!0%*4%-(!D!/B"`M8!!

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l_E8!!"!-%*6()5*%')!5(,*+66+*(!*%$$*+&+#'%*+!)/!;PR!5+//B%$$(*'(!'('%/+!-%/(*)-(8!!!

< V'1,(#'-')"!5)1*+')-)!&)!$(&&(#(!1&%*+!$+*!)/!'*%''%4+#'(!5+//B+5+4%3!&($*%''1''(!#+)!$%2)+#')!)$+*,(/+4)-)8!"#!:1+&'(!-%&(!)/!/(*(!)4$)+7(!&+*,+!%#-.+!%!0%*!&e!-.+!)/!*+#+!+/)4)#)!$)F!&(5)(!5)!:1+//(!-.+!%&&(*6+3!+&&+#5(!)#!:1+&')!-%&)!)4$(#+#'+!/B%''),%2)(#+!5+/!O`M8!9,,)%4+#'+3!1#%!5)+'%!)$(&(5)-%!?!-(41#:1+!)#5)&$+#&%6)/+!$+*!*+#5+*+!+00)-%-+!/%!'+*%$)%8!!!

Page 12: sbobinature nefro_0 - SkyDrive

< !,$+'%"00')"*#'L#,$/C$#'-")"!$%2)+#')!-(#!&)#5*(4+!#+0*(&)-%!.%##(!1#!*)&-.)(!5+/!SPR!5)!%#5%*+!)#-(#'*(!%5!+$)&(5)!'*(46(+46(/)-)3!$('+#2)%/4+#'+!0%'%/)!Y+&G!+46(/)%!$(/4(#%*+Z8!E%!'*(46(&)!5+//%!,+#%!*+#%/+!?!-%*%''+*)&')-%!5+//%!&)#5*(4+!#+0*(&)-%!4%!#(#!?!/B+,+#)+#2%!$)F!0*+:1+#'+8!aB!-(#&)7/)%6)/+!/B)4$)+7(!5+//B+$%*)#%!%!6%&&(!$+&(!4(/+-(/%*+!#+)!-%&)!%5!%/'(!*)&-.)(8!!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

Page 13: sbobinature nefro_0 - SkyDrive

R*01++'-'(*2")U(*"%()S-1#")!

EB)#&100)-)+#2%!*+#%/+!%-1'%3!$+*!5+0)#)2)(#+3!?!1#%!-(#5)2)(#+!-.+!&)!&,)/1$$%!#+//B%*-(!5)!(*+!(!$(-.)!7)(*#)8!O)!'*%''%!5)!1#!+#(*4+!$*(6/+4%!-/)#)-(!-.+!$1N!-%$)'%*+!5)!5(,+*!7+&')*+!$*%')-%4+#'+!)#!:1%/&)%&)!*+$%*'(8!EB)#-)5+#2%!5)!:1+&'%!&)#5*(4+!?!5)!IPPP<KPPP!-%&)!$+*!4)/)(#+!5)!$+*&(#+G!#+//+!'+*%$)+!)#'+#&),+!51+!'+*2)!5+)!$%2)+#')!*)-(,+*%')!&(#(!)#!"`M8!E%!4(*'%/)'>!5)!:1+&'%!-(#5)2)(#+!?!&1$+*)(*+!%/!SPR3!$*($*)(!$+*-.[!+&&%!?!)/!&+7#%/+!5)!1#(!&-(4$+#&(!41/')(*7%#(!'+*4)#%/+3!%#-.+!)#!-%&(!5)!$%'(/(7)+!#(#!$*)4)'),%4+#'+!*+#%/)8!!

V*%5)2)(#%/4+#'+!,)+#+!5+0)#)'%!-(4+!*)512)(#+!)4$*(,,)&%!5+//%!01#2)(#%/)'>!*+#%/+!-.+!5+'+*4)#%!%--141/(!5)!1*+%!+!5)!%/'*+!&(&'%#2+!'(&&)-.+!#(*4%/4+#'+!+/)4)#%'+!-(#!/+!1*)#+!+!&:1)/)6*)(!)5*(+/+''*(/)')-(8!!

M$$%*+!:1)#5)!0(#5%4+#'%/+!/%!$*(#'%!)5+#')0)-%2)(#+!5+//B"`M!#+)!$%2)+#')!(&$+5%/)22%')3!+!$+*&)#(!#+)!$%2)+#')!-.+!/%!&,)/1$$%#(!)#!-(41#)'>8!\(4+!%66)%4(!,)&'(!$%*/%#5(!5+)!$%*%4+'*)!5)!01#2)(#%/)'>!*+#%/+3!/%!-*+%')#)#+4)%!?!$(-(!1')/)22%6)/+!$+*!4+''+*+!)#!+,)5+#2%!1#B"`MG!:1+&'(3!#(#!$+*-.[!)#!:1+&'%!-(#5)2)(#+!)/!$%2)+#'+!#(#!%66)%!1#!*)%/2(!5+//%!-*+%')#)#+4)%3!4%!$+*-.[!+&)&'+!1#%!/%'+#2%!'*%!)#&(*7+#2%!5+//B"`M!+!*)%/2(!5+//%!-*+%')#)#%8!\)(?3!:1%#5(!#()!,+5)%4(!)/!*)%/2(!5+//%!-*+%')#)#+4)%3!/B)#&100)-)+#2%!*+#%/+!%-1'%!(*4%)!.%!5+'+*4)#%'(!/B+g)'1&!5+/!$%2)+#'+!($$1*+!?!&'%'%!)#!:1%/-.+!4(5(!*)&(/'%8!!

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`M!?!5(,1'(!%5!1#!5%##(!'161/%*+8!

!

!

\/%&&)0)-%2)(#+!5+//B"`M!

H('+*!*)-(#(&-+*+!$*+-(-+4+#'+!/B"`M!?!+&&+#2)%/+3!$+*-.[!&+!&)!)#'+*,)+#+!-(#!-+/+*)'>!?!$(&&)6)/+!&%/,%*+!)/!$%2)+#'+!+!*)$*)&')#%*+!/%!&1%!01#2)(#+!*+#%/+8!H+*!:1+&'(3!&(#(!&'%'+!)5+%')!-*)'+*)!)#!7*%5(!5)!%)1'%*-)!)#!:1+&'(!-%4$(8!!

E%!-/%&&)0)-%2)(#+!6%&%'%!&1)!-*)'+*)!`"kEa3!1&%'%!5%)!#+0*(/(7)3!?!%#-(*%!$(-(!1&%'%!)#!%/'*)!%46)+#')!-/)#)-)3!4%!?!4(/'(!1')/+!$+*!-%$)*+!)#!4(5(!%66%&'%#2%!&+4$/)-+!&+!)/!$%2)+#'+!&')%!&,)/1$$%#5(!1#B"`M3!$*)4%!-.+!&)!,+*)0)-.)!)/!*)%/2(!5+//%!-*+%')#)#%3!-.+!#(#!$(&&)%4(!$+*4+''+*-)!5)!%''+#5+*+8!

Page 14: sbobinature nefro_0 - SkyDrive

!

"!-*)'+*)!`"kEa!,%##(!/+'')!)#!:1+&'(!4(5(G!

! U'0W)I,'0-.'$)X3')RUSYZG!%14+#'(!5+//%!-*+%')#)#%!5)!W3S!,(/'+3!*)512)(#+!5+//%!,+/(-)'>!5)!0)/'*%2)(#+!7/(4+*1/%*+!Yhk^Z!5+/!ISR!(!5+//%!5)1*+&)!%!4+#(!5)!P3S!4/U]7!$+*!$%#,()Z)$,([)

! R*\1,])I3"**$)X,(*"%(YJQ!*%55($$)(!5+//%!-*+%')#)#%3!*)512)(#+!5+/!hk^!5+/!SPR!(!(!5+//%!5)1*+&)!%!4+#(!5)!P3S!4/U]7!$+*!(/'*+!WI!(*+C!

! ^"'%1,()I'*01++'-'(*2")X3('),(*'YJQ!%14+#'(!5)!'*+!,(/'+!5+//%!-*+%')#)#%3!*)512)(#+!5+/!hk^!5+/!=SR!(!5+//%!5)1*+&)!%!4+#(!5)!P3S!4/U]7!$+*!(/'*+!IQ!(*+!Y(/)71*)%Z!(!%#1*)%!$+*!WI!(*+C!

! _$00)I6(,3'#")X3')+1*2'$*(),(*"%(YJQ!$+*5)'%!-(4$/+'%!5+//%!01#2)(#+!*+#%/+!-.+!*)-.)+5+!'+*$)%!&(&')'1'),%!Y5)%/)&)Z!$+*!$)F!5)!:1%''*(!&+'')4%#+C!

! 4*3L0#"&()W'3*(])3'0("0()I'*01++'-'(*2"),(*"%()#(,/'*"%(JQ)1*+4)%3!-)(?!$+*5)'%!-(4$/+'%!5+//%!01#2)(#+!*+#%/+!-.+!*)-.)+5+!'+*%$)%!&(&')'1'),%!Y5)%/)&)Z!$+*!$)F!5)!'*+!4+&)8)!

)!<Q!9/)71*)%!m!jQSP!--!1*)#+!U!IQ!(*+!C!M#1*)%!m!j!WPP!--!1*)#+UIQ!(*+!!`+-+#'+4+#'+!?!&'%'%!$*($(&'%!1#%!#1(,%!-/%&&)0)-%2)(#+!6%&%'%!)#!$%*'+!&1)!-*)'+*)!`"kEaG!&)!'*%''%!5+)!-*)'+*)!Mn"b8!"/!0)#+!?!:1+//(!5)!*+#5+*+!)/!'1''(!%#-(*%!$)F!4%#+77+,(/+!&1/!$)%#(!-/)#)-(8!"!-*)'+*)!Mn"b!$*($(#7(#(3!)#(/'*+3!5)!%5(''%*+!/%!5+0)#)2)(#+!$)F!7+#+*)-%!5)!@M-1'+!])5#+o!)#p1*oA8!!

A modification of the RIFLE criteria has been proposed by the Acute Kidney Injury Network. The AKIN proposed both diagnostic criteria for ARF and a staging

system that was based on the RIFLE criteria. In addition, the term acute kidney injury (AKI) was proposed to represent the entire spectrum of acute renal failure.

* Modified from RIFLE (Risk, Injury, Failure, Loss, and End-stage kidney disease) criteria. The staging system proposed is a highly sensitive interim staging system and is based on recent data indicating that a small change in serum creatinine influences outcome. Only one criterion (creatinine or urine output) has to be fulfilled to qualify for a stage. !200 to 300 percent increase = 2- to 3-fold increase. "Given wide variation in indications and timing of initiation of renal replacement therapy (RRT), individuals who receive RRT are considered to have met the criteria for stage 3 irrespective of the stage they are in at the time of RRT.

Page 15: sbobinature nefro_0 - SkyDrive

b+//%!$*%')-%!-/)#)-%!)!-*)'+*)!Mn"b!&+46*%#(!)#!+00+'')!$)F!0%-)/4+#'+!%''1%6)/)8!!b1(,)!$(&&)6)/)!4%*]+*&!!`)%&&14+#5(!:1%#'(!5+''(!0)#(*%3!/%!5)%7#(&)!5)!)#&100)-)+#2%!*+#%/+!%-1'%!%/!7)(*#(!5B(77)!$1N!6%&%*&)!&1//%!,%/1'%2)(#+!5)!1#!)#&)+4+!5)!$%*%4+'*)!-.+!&(#(!$()!)#'+7*%')!&+-(#5(!)!-*)'+*)!`"kEa!(!&+-(#5(!)!-*)'+*)!Mn"bG!&)!'*%''%!$+*%/'*(!5)!4)&1*%2)(#)!&+4$/)-)!5%!+00+''1%*+!&1!&%#71+!+5!1*)#+3!:1)#5)!4(/'(!*%$)5+8!L1+&'(!&)7#)0)-%3!$+*N3!-.+!#(#!+&)&'+!1#!&)#7(/(!4%*-%'(*+!-.+!-)!-(#&+#'%!5)!0%*+!5)%7#(&)!5)!"`MG!/%!-*+%')#)#%3!-(4+!&)!?!5+''(3!&)!)##%/2%!-(#!1#%!/%'+#2%!+--+&&),%3!+!#(#!?!%00)5%6)/+!)#!1#!$%2)+#'+!-.+!#(#!&)!'*(,%!%//(!&'+%5o<&'%'+8!H+*!/B)#0%*'(!5+/!4)(-%*5)(3!)#,+-+3!#+/!-(*&(!5+7/)!%##)!&)%4(!&'%')!)#!7*%5(!5)!)5+#')0)-%*+!4%*-%'(*)!&+4$*+!$)F!&+#&)6)/)3!$*+-(-)!+!&$+-)0)-)3!+!&)%4(!&'%')!-%$%-)!5)!*)51**+!#('+,(/4+#'+!/%!4(*'%/)'>!7*%2)+!%//%!5)%7#(&)!&+4$*+!$)F!$*+-(-+8!H+*!:1+&'(!-B?!4(/'(!)#'+*+&&+!)#'(*#(!%//B)#5),)51%2)(#+!5)!#1(,)!$(&&)6)/)!4%*]+*&!5)!5%##(!*+#%/+!%-1'(8!E%!-'0#"#'*");!?!1#(!5)!:1+&')!#1(,)!4%*]+*&G!)#!-(*&(!5)!$%'(/(7)%!*+#%/+!-*(#)-%!#(#!?!4(/'(!1')/+3!4%!)#!-(*&(!5)!"`M!/%!&1%!1')/)'>!&+46*%!+&&+*+!#('+,(/+8!"#0%'')3!/%!-)&'%')#%!\!&)+*)-%!%14+#'%!-(#!%#')-)$(!5)!-)*-%!IQ<QJ!(*+!*)&$+''(!%//B)##%/2%4+#'(!5+//%!-*+%')#)#%8!T#!+/+4+#'(!5%!-(#&)5+*%*+3!$+*N3!?!-.+!/%!-)&'%')#%3!$)F!-.+!1#!4%*]+*!5)!5%##(!*+#%/+3!?!1#!/",W(,)3'),'312'$*()3(%)`^U9)T#!%/'*(!4%*]+*!$*(4+''+#'+!?!/%!%'6$-"%'*")"00$-'"#")"%%")&(%"#'*"0')*(1#,$+'%")I=`S_J3!1#%!$*('+)#%!-.+!,)+#+!*)/%&-)%'%!#(#!%$$+#%!&)!,+*)0)-%!1#!5%##(!*+#%/+3!%7+#5(!:1)#5)!-(4+!1#%!&(*'%!5)!$*('+)#%!5)!0%&+!%-1'%!*+#%/+8!!!"#!5+0)#)'),%3!:1)#5)3!/%!5)%7#(&)!5)!"`M!&1/!*)&-(#'*(!5)!1#!)#-*+4+#'(!5+//%!-*+%')#)#+4)%!Y&+!+*%!#('(!)/!,%/(*+!6%&%/+3!(,,)%4+#'+Z!(!5)!1#%!&)#'(4%'(/(7)%!%-1'%!5)!*)512)(#+!(!'('%/+!&-(4$%*&%!5+/!0/1&&(!1*)#%*)(G!#+//%!7*%#!$%*'+!5+)!-%&)3!4(/'(!&+4$/)-+4+#'+3!/%!5)%7#(&)!&)!0%!#+/!4(4+#'(!)#!-1)!)/!$%2)+#'+!&4+''+!5)!1*)#%*+!(!#+/!4(4+#'(!)#!-1)!-)!&)!*+#5+!-(#'(!-.+!/%!&1%!5)1*+&)!?!+&'*+4%4+#'+!-(#'*%''%8!!!O)'1%2)(#)!-/)#)-.+!!EB"`M!?!-%1&%'%!:1%&)!&+4$*+!5%!1#%!*)512)(#+!5+//%!,(/+4)%3!%&&(/1'%!(!*+/%'),%!Y)#!'+*4)#)3!:1)#5)3!5)!h\aZ8!b+//%!4%77)(*!$%*'+!5+)!-%&)3!)!$%2)+#')!-.+!&,)/1$$%#(!"`M!&(#(!7)>!*)-(,+*%')!+!/B)#&100)-)+#2%!*+#%/+!&)!$*+&+#'%!-(4+!-(4$/)-%2)(#+!5+/!$%2)+#'+!*)-(,+*%'(!(!)#!'+*%$)%!)#'+#&),%8!"#5),)51)!D!&$+-)%/4+#'+!%#2)%#)!D!)#!'+*%$)%!-(#!0%*4%-)!)$(,(/+4)22%#')!Y5)1*+')-)3!M\a<"3!&%*'%#)Z!$(&&(#(!&,)/1$$%*+!"`M!&+!&($*%77)1#7(#(!-(#5)2)(#)!$%*')-(/%*)G!1#!-%&(!')$)-(!$1N!+&&+*+!:1+//(!5)!$%2)+#')!%#2)%#)!-.+3!51*%#'+!)/!-%/5(!+&'),(3!,%##(!)#-(#'*(!%!5)&)5*%'%2)(#+8!"#!:1+&'(!-%&(!/%!5)&)5*%'%2)(#+3!-(46)#%'%!%//B+00+''(!5+)!0%*4%-)3!5+'+*4)#%!/B"`M8!T#B%/'*%!-%1&%!&+4$*+!$)F!)4$(*'%#'+!?!/B1')/)22(!5+)!4+22)!5)!-(#'*%&'(!$+*!)4%7)#7!Y&($*%''1''(!)#!%46)'(!5)!-.)*1*7)%!,%&-(/%*+ZG!$%2)+#')!%#2)%#)!-(#!1#%!01#2)(#+!*+#%/+!&')4%'%!-(#!/%!0(*41/%!5)!\(-]-*(0'!%/!5)!&(''(!5+)!;P!4/U4)#!Y%!4%77)(*!*%7)(#+!&+!jKP!4/U4)#Z3!$+*!5)!$)F!5)%6+')-)3!.%##(!1#!)4$(*'%#'+!*)&-.)(!5)!&,)/1$$%*+!"`M8!L1)#5)3!/B)#&100)-)+#2%!*+#%/+!%-1'%!?!,","/(*#()-"10"#")3")1*")6"#$%$&'"),(*"%()6,'/'#'7"3!+!:1%&)!&+4$*+!0(-$*3",'")")a1"%-$05"%#,$9!O+!?!,+*(!-.+!0%*+!5)%7#(&)!$*+-(-+!5)!"`M!$1N!+&&+*+!5)00)-)/+3!1#%!,(/'%!-.+!/%!-(#5)2)(#+!&)!&,)/1$$%!/%!5)%7#(&)!?!*+/%'),%4+#'+!%7+,(/+3!+!7+#+*%/4+#'+!/%!-%1&%!&-%'+#%#'+!?!%66%&'%#2%!+,)5+#'+8!L1)#5)3!/+!-%1&+!&(#(!0(#5%4+#'%4+#'+G!

< U'312'$*()3(%%")7$%(/'")"00$%1#")I6,(L,(*"%(J)< U'312'$*()3(%%")7$%(/'")(++'-"-()I6,(L,(*"%(J)< 8$00'-')()+",/"-')-.()-"10'*$)3"**$)#1C1%",()I,(*"%(J)< !"#$%$&'(),(*"%')I,(*"%(J)< H0#,12'$*')3(%%()7'()1,'*",'()I6$0#L,(*"%(J)

Page 16: sbobinature nefro_0 - SkyDrive

9/'*+!%//B1*+%3!%7/)!+/+''*(/)')!&)+*)-)3!/Ba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

!\%1&+!$*+<*+#%/)!!E+!-%1&+!$*+<*+#%/)!&(#(!'1''+!:1+//+!-.+!5+'+*4)#%#(!1#%!*)512)(#+!5+//%!,(/+4)%3!&)%!)#!&+#&(!%&&(/1'(!-.+!)#!&+#&(!*+/%'),(8!V*%!/+!*)512)(#)!5+//%!,(/+4)%!%&&(/1'%!*)-(*5)%4(!:1)#5)!(/$,,"&'()/"00'7(!+!:1%/&)%&)!&)'1%2)(#+!5)!3(6%(2'$*()3')7$%1/(3!-(4$*+&(!/B1')/)22(!5)!0%*4%-)!)$(,(/+4)22%#')!-(4+!)!5)1*+')-)3!-.+!$(&&(#(!$*+-)$)'%*+!1/'+*)(*4+#'+!+,+#'1%/)!&)'1%2)(#)!5)!*)512)(#+!5+//%!,(/+4)%8!!!E%!*)512)(#+!5+/!h\a!&)!.%!#+)!-%&)!5)!,'3$##")6(,+$,/"*-()-",3'"-"!Y&-(4$+#&(!-%*5)%-(!%-1'(!(!%77*%,%4+#'(!5)!&-(4$+#&(!-*(#)-(Z!+!)#!-%&(!5)!-',,$0')(6"#'-"!&-(4$+#&%'%!-(#!"0-'#(3!%//(*-.[!&)!,+*)0)-%!1#%!-(#5)2)(#+!5)!1#5+*0)//)#78!b+/!-)**(')-(!1#%!&)'1%2)(#+!%!*)&-.)(!$%*')-(/%*4+#'+!+/+,%'(!5)!"`M!?!/%!$%*%-+#'+&)!+,%-1%'),%G!&+!#(#!&)!1&%#(!-(**+''%4+#'+!)!$/%&4%!+g$%#5+*&!!-(#'+&'1%/4+#'+!%//%!$*(-+51*%3!&)!*)&-.)%!5)!$*(,(-%*+!1#%!7*%,)&&)4%!)$(,(/+4)%8!M#-.+!/%!0(60'!+!:1%/&)%&)!%/'*(!')$(!5)!&.(-]!&(#(!-%1&+!5)!*)512)(#+!%-1'%!5+/!h\a8!!M#-.+!/%!*)512)(#+!)4$*(,,)&%!5+/!0/1&&(!)#!%*'+*)%!*+#%/+!I0#(*$0'G)#,$/C$0'G)(/C$%'"J!$1N!5+'+*4)#%*+!"`M8!!"#0)#+3!*)-(*5)%4(!-(4+!')^S=<)I0$6,"##1##$)S<SJ)()S;4LRE0",#"*'!$(&&%#(!+&&+*+!-%1&%!5)!"`M8!M\a<"!+!O%*'%#)3!#+//%!0%'')&$+-)+3!&(#(!4(/'(!$+*)-(/(&)!#+7/)!)#5),)51)!)#!-1)!/%!,(/+4)%!+00)-%-+!,)+#+!4%#'+#1'%!+&&+#2)%/4+#'+!7*%2)+!%/!&)&'+4%!*+#)#%<%#7)('+#&)#%3!+!:1+&')!&(#(!&($*%''1''(!)!&(77+'')!-(#!&'+#(&)!6)/%'+*%/+!5+//B%*'+*)%!*+#%/+!+!-(#!&-(4$+#&(!-%*5)%-(8!"!kMbO3!)#,+-+3!%7)&-(#(!)#)6+#5(!/%!&)#'+&)!5)!$*(&'%7/%#5)#+!,%&(5)/%'%'*)-)!)#!&+5+!*+#%/+3!+!:1+&'(!$1N!5+'+*4)#%*+!)#!$%*')-(/%*)!

!"#$$%&'#()*+#*,+-#.)/+'#0$1$+)2+#'031+/1*#"+2#%"0/1+

Page 17: sbobinature nefro_0 - SkyDrive

-(#5)2)(#)!1#(!&'%'(!5)!#+-*(&)!)&-.+4)-%!%!/),+//(!'161/%*+8!!EB"`M!5%!-%1&+!$*+<*+#%/)!?!)#)2)%/4+#'+!1#B)#&100)-)+#2%!*+#%/+!+1*2'$*"%(G!&+3!$+*N3!#(#!,)+#+!*)4(&&%!+00)-%-+4+#'+!+!*%$)5%4+#'+!/%!-%1&%!&-%'+#%#'+3!)/!5%##(!01#2)(#%/+!5+'+*4)#%!%#-.+!/%!#+-*(&)!'161/%*+!&1!6%&+!)&-.+4)-%3!+!%!:1+&'(!$1#'(!&)!)#&'%1*%!%#-.+!1#%!-(4$(#+#'+!$,&"*'-"),(*"%(3!-)(?!/%!#+-*(&)!'161/%*+!%-1'%8!!

!

!!!\%1&+!`+#%/)!!\)(?3!+,+#')!-.+!&)!,+*)0)-%#(!$*)4)'),%4+#'+!#+/!$%*+#-.)4%!*+#%/+8!O(#(!-%1&+!%66%&'%#2%!*%*+!5)!"`M8!

< ;"10()7"0-$%",'Q)#+//+!,%&-1/)')!+!#+//B)$+*'+#&)(#+!4%/)7#%!/B%/'+*%2)(#+!5+//%!$+*,)+'>!5+//+!%*'+*)(/+!5+/!$%*+#-.)4%!*+#%/+!$1N!$(*'%*+!%//B"`M8!

< `%$/(,1%$*(+,'#()"-1#"!< =(+,'#()'*#(,0#'2'"%()"-1#"!< =(-,$0')#1C1%",()"-1#"!

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q+#-+<r(#+&!Y*+#+!5%!4)+/(4%Z8!

Ipoperfusione renale

Ischemia dei nefroni corticali superficiali e riduzione del GFR

Innesco di meccanismi di compenso del GFR

efficacia del compenso

SI NO

recupero funzionale

viraggio verso il danno organico

ischemico

pre-renale (funzionale)!

renale (organica ischemica)!

Diagnosi differenziale della Insufficienza Renale Acuta

Osmolarità urinaria (mOsm/L) ! > 500 < 350 sensibilità del rene

all’ADH

Frazione di escrezione del sodio

< 1 > 1 (>2 NTA)! sensibilità del rene

al feedback glomerulo-tubulare

sodiuria (mEq/die) ! < 20 > 40 idem

azotemia/creatininemia > 20 < 10 idem

risposta diuretica al mannitolo SI NO

sensibilità renale agli stimoli diuretici osmotici

Page 18: sbobinature nefro_0 - SkyDrive

!!\%1&+!$(&'<*+#%/)!!O(&'%#2)%/4+#'+3!&(#(!'1''+!/+!-%1&+!5)!(--/1&)(#+!5+//+!,)+!1*)#%*)+8!O)!'*%''%!5)!&'1%2)(#)!(*4%)!$)1''(&'(!*%*+8!

!)O)#'(4)!!9/'*+!%//%!*)512)(#+!5+//B(1'$1'!1*)#%*)(3!)/!$%2)+#'+!$1N!$*+&+#'%*&)!-(#!&)#'(4)!-.+!$(&&(#(!+&&+*+!)#5)-%'),)!-)*-%!/%!-%1&%!5+//B"`M8!H+*!+&+4$)(3!&+!/B"`M!?!&'%'%!-%1&%'%!5%!1#!)#0%*'(!%-1'(!5+/!4)(-%*5)(3!,+*(&)4)/4+#'+!)/!$%2)+#'+!&)!$*+&+#'+*>!-(#!)/!-(*'+(!&)#'(4%'(/(7)-(!5+//B"XM8!9$$1*+3!#+/!-%&(!5)!1#%!,%&-1/)'+!&)&'+4)-%!-.+!-()#,(/7+!%#-.+!/+!%*'+*)+!*+#%/)3!&)!$('*%##(!*)&-(#'*%*+!)!&+7#)!5)!/(-%/)22%2)(#+!5B(*7%#(!5+/!$*(-+&&(!,%&-1/)')-(U)#0)%44%'(*)(!Y+&G!5%##(!$(/4(#%*+3!%*'*)'+3!0+66*+Z8!"#(/'*+3!)/!:1%5*(!-/)#)-(!*)&+#'+!5+//+!%/'+*%2)(#)!-%1&%'+!5%//B"`M!&'+&&%G!

< R6(,W"%'(/'"Q)L1%#5(!/B"`M!*%77)1#7+!+/+,%')!/),+//)!5)!7*%,)'>!/B)$+*]%/)+4)%!$1N!+&&+*+!1#%!,+*%!+!$*($*)%!+4+*7+#2%!4+5)-%G!)!/),+//)!5)!$('%&&)(!$(&&(#(!&1$+*%*+!)!;3S!4a:UE!+!)#!'%/!-%&(!?!%/'(!)/!*)&-.)(!-.+!&)!&,)/1$$)!1#B%*)'4)%!-%*5)%-%!4%/)7#%8!

< S2$#(/'")/$%#$)(%(7"#"!$1N!5+'+*4)#%*+!1#%!&+*)+!5)!%/'+*%2)(#)3!&$+-)%/4+#'+!%#(*+&&)%3!#%1&+%3!,(4)'(3!-(#,1/&)(#)3!4(5)0)-%2)(#)!5+//(!&'%'(!5)!-(&-)+#2%8!Y,#!%2('+4)%m!II<Q;!47U5E!Z8!

< V$%$,()"%)+'"*-$!< S0#(*'")Y$1N!+&&+*+!-%1&%'%!5%!1#B%#+4)%!5%!5+0)-)'!5)!aH9Z!< R6(,#(*0'$*(!< R6(,+$0+$,(/'"LR6$-"%-(/'"!< S-'3$0')/(#"C$%'-"!?!1#%!-(&'%#'+!

!

!!

•  Calcolosi urinaria •  Neoplasie delle vie urinarie o extraurinarie (specie della pelvi) ! •  Ipertrofia prostatica •  Fibrosi retroperitoneale •  Emorragie retroperitoneali •  Legatura accidentale degli ureteri •  Stenosi cicatriziali da flogosi croniche della pelvi •  Presenza di coaguli nelle vie urinarie •  Stenosi dell’uretra (valvole congenite, stenosi cicatriziali, fimosi) !

Cause più frequenti:

La ostruzione urinaria favorisce l’infezione urinaria e la calcolosi e pertanto va rapidamente risolta o rimuovendo, se rimovibile , l’ostacolo al deflusso urinario, oppure deviando all’esterno le urine (sonde nefrostomiche o stent endoluminali).

La risoluzione della ostruzione provoca rapida ripresa della funzione renale, eccetto che nel caso in cui la ostruzione sia stata molto protratta ed abbia provocato danni irreversibili al parenchma renale (danno ischemico “da compressione” operato dalla sovradistensione della pelvi e dei bacinetti) !

1) Contrazione della diuresi (o diuresi conservata)!

2) Ritenzione cataboliti azotati (innalzamento della azotemia, della creatininemia, della uricemia, encefalopatia, altosi, nausea, vomito, cefalea, pericardite uremica) !

3) Ritenzione idrica (se persistente contrazione della diuresi) ! (edema, versamenti cavità sierose ,ipertensione arteriosa, sovraccarico cardiaco sino all’edema polmonare acuto, aritmie) !

4) Ritenzione salina (iperpotassiemia, iperfosforemia con conseguente ipocalcemia)!

5) Ritenzione acidi organici (fosfati e solfati) ! (acidosi metabolica con polipnea compensatoria ) !

Page 19: sbobinature nefro_0 - SkyDrive

!!!_1*%'%!5+//%!4%/%'')%!H+*!5+0)#)2)(#+3!/B"`M!?!1#%!-(#5)2)(#+!-.+!&)!&,)/1$$%!+!&)!*)&(/,+!Y-(#!/%!71%*)7)(#+!(!/%!4(*'+Z!#+/!7)*(!5)!$(-.)!7)(*#)8!O+!&)!&1$+*%#(!/+!Q!&+'')4%#+3!&)!5+,+!$%*/%*+!5)!)#&100)-)+#2%!*+#%/+!-*(#)-%G!)/!$%2)+#'+!?!&($*%,,)&&1'(!4%!#(#!?!*)1&-)'(!%!&1$+*%*+!/B+,+#'(!%-1'(!*+-1$+*%#5(!/%!01#2)(#+!*+#%/+3!-.+!$+*'%#'(!?!)**+,+*&)6)/4+#'+!5)4)#1)'%8!!!!O'(*)%!b%'1*%/+!!EB"`M!?!-(#&)5+*%'%!1#%!-(#5)2)(#+!*+,+*&)6)/+3!4%!)#!*+/%2)(#+!%//B+#')'>!5+/!5%##(!-.+!&)!&,)/1$$%8!b+/!!iPR!5+)!-%&)!)/!$%2)+#'+!&1$+*%!/B+$)&(5)(!+!$1N!'(*#%*+!%!-%&%!-(#!1#%!01#2)(#+!*+#%/+!-.+!7/)!-(#&+#'+!1#%!,)'%!%&&(/1'%4+#'+!#(*4%/+8!L1+&'(!#(#!&)7#)0)-%3!$+*N3!-.+!#(#!&)!&)%!,+*)0)-%'(!1#!5%##(!*+#%/+G!)#0%'')3!?!4(/'(!$*(6%6)/+!-.+!&)!&)%#(!$+*&)!4(/')&&)4)!#+0*(#)8!\(4+!&%$$)%4(3!$+*N3!/%!01#2)(#+!*+#%/+!#(#!5+-%5+!0)#-.[!#(#!&)!$+*5+!$)F!5+/!iSR!5+//%!4%&&%!5)!#+0*(#)8!"/!$%2)+#'+3!:1)#5)3!$1*!+&&+#5(!5)4+&&(!)#!61(#+!-(#5)2)(#)!+!-(#!/),+//)!5)!-*+%')#)#%!-(4$/+'%4+#'+!#(*4%/)3!%,+#5(!$+*&(!1#%!-+*'%!:1('%!5)!#+0*(#)!%,*>!1#%!*)&+*,%!01#2)(#%/+!4)#(*+!5%!(*%!)#!$()8!!\)*-%!)/!IS<KPR!5+)!$%2)+#')!&,)/1$$%#(!1#!5+0)-)'!*)/+,%6)/+!%#-.+!-(#!/%!-*+%')#)#+4)%8!T#%!-+*'%!$+*-+#'1%/+!5)!$%2)+#')3!)#(/'*+3!&,)/1$$%!)#&100)-)+#2%!*+#%/+!+#5<&'%7+8!!X%#%7+4+#'!!E%!'+*%$)%!?!)#!01#2)(#+!5+//%!-"10"!-.+!.%!5+'+*4)#%'(!/B"`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q)&(7#%!&+4$*+!&'%*+!%''+#')!%//+!$(&&)6)/)!)#0+2)(#)3!&$+-)%/4+#'+!&+!)/!$%2)+#'+!?!)#!'+*%$)%!)#'+#&),%3!+5!+,+#'1%/4+#'+!'*%''%*/+!)#!4(5(!%77*+&&),(!-(#!%#')6)(')-)!4(/'(!+00)-%-)!Y+&G!-%*6%$+#+4)-)3!7/)-($+$')5)Z8!!H+*!)/!*+&'(3!)#!-%&)!&$+-)0)-)G!

6) Anemia e pallore della cute e delle mucose visibili

9) Segni e sintomi riferibili alla causa di insufficienza renale

7) Suscettibilità alle infezioni

8) Suscettibilità alle emorragie

•  esposizione recente a farmaci o tossici •  episodi recenti di possibile protratta ipoperfusione renale •  segni di rabdomiolisi, di emolisi, di colestasi grave •  ipocomplementemia, ematuria, sedimento attivo •  manovre endovascolari recenti •  segni di microangiopatia trombotica •  artralgie, porpora, positività agli ANCA o altri autoanticorpi •  eosinofilia ematica

Page 20: sbobinature nefro_0 - SkyDrive

< "#!-%&(!5)!&+$&)3!&)!'*%''%!/B)#0+2)(#+3!+!&)!)4$)+7%#(!&+44%)!7/1-(-(*')-()5)!%!6%&&+!5(&)!+!%4)#+!,%&(%''),+!:1%/(*%!/%!&)'1%2)(#+!&)%!$%*')-(/%*4+#'+!7*%,+8!!

< "#!-%&(!5)!)#'(&&)-%2)(#+3!0(#5%4+#'%/4+#'+!&)!0(*2%!/%!5)1*+&)!+!&+44%)!&)!)4$)+7%#(!-.+/%#')8!

T#!%&$+''(!)4$(*'%#'+!?!-%$)*+!:1%#5(!)/!$%2)+#'+!,%5%!5)%/)22%'(G!)#!7+#+*%/+!&)!%&&14(#(!-(4+!-*)'+*)!$+*!/%!5)%/)&)!1#%!&+,+*%!)$+*$('%&&)+4)%3!1#B)$+*%2('+4)%!7*%,+!+!1#%!&+,+*%!%-)5(&)C!:1%#5(!$()!&)!&,)/1$$%#(!)!&)#'(4)!+!)!&+7#)!5+//B1*+4)%!Y+#-+0%/($%')%3!#+1*($%')%3!$+*)-%*5)'+Z3!%!4%77)(*!*%7)(#+!/%!5)%/)&)!?!#+-+&&%*)%8!

!

!!

!

!

!

!

!

!

!

!

!

!

!

!

!

Si osserva generalmente dopo circa 20 giorni dall’esordio della insufficienza renale acuta.

Sono fattori che si oppongono alla rigenerazione epiteliale:

intensa vasocostrizione corticale

liberazione di enzimi litici e di radicali dell’ossigeno da parte di leucociti migrati dal circolo ematico, che affluiscono attorno ai tubuli danneggiati

distacco di cellule necrotiche epiteliali dalla membrana basale tubulare, con ostruzione del lume tubulare, aumento della pressione endoluminale e retrofiltrazione di preurina nell’interstizio

liberazione di enzimi proteasici (es. caspasi) da parte di cellule epiteliali danneggiate

danno esteso della membrana basale tubulare (tubuloressi) !

pre-esistente insufficienza renale cronica (IRA “sovrapposta ad IRC”) !

Page 21: sbobinature nefro_0 - SkyDrive

=(+,$6"#'")V'"C(#'-")

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

L1)#5)3!/%!#+0*($%')%!5)%6+')-%!?!1#%!$%'(/(7)%!-.+!3(7()(00(,(),'-(,-"#")0'0#(/"#'-"/(*#(!#+/!$%2)+#'+!5)%6+')-(8!E+!'+4$)&')-.+!$+*!)#)2)%*+!/%!*)-+*-%!,%*)%#(G!#+/!5)%6+')-(!5)!')$(!"!&)!5(,*+66+!)#)2)%*+!%!*)-+*-%*+!*$*)6,'/")3')?)"**'!5%//B+&(*5)(!5+//%!4%/%'')%8!b+/!$%2)+#'+!-(#!5)%6+'+!5)!')$(!""3!)#,+-+3!7"),'-(,-"#")01C'#$!$+*-.[!D!+&&+#5(!)#!:1+&')!)#5),)51)!)/!5)%6+'+!$*%')-%4+#'+!%&)#'(4%')-(!D!#(#!?!$(&&)6)/+!5%'%*+!/B)#)2)(!5+//%!4%/%'')%!+!:1%#')0)-%*+!-(#!+&%''+22%!/%!51*%'%!5+/!4%#-%'(!-(#'*(//(!7/)-+4)-(8!!

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k`8!b+/!5)%6+'+!5)!')$(!"!/%!0%&+!5)!)$+*0)/'*%2)(#+!?!:1%&)!4%'+4%')-%3!&)!,+5+!$*%')-%4+#'+!&+4$*+G!)#0%'')!'*(,+*+4(!0$&&(##')&'$7"*')-$*)3'"C(#()3')#'6$)R)()7"%$,')3')-,("#'*'*(/'")6",#'-$%",/(*#()C"00'!)#!*%$$(*'(!%//%!/(*(!4%&&%!41&-(/%*+!YP3Q<P3S!47U5EZ8!O+!%#5)%4(!%!0%*+!1#%!-*+%')#)#+!-/+%*%#-+!)#!:1+&')!&(77+'')3!,+#7(#(!01(*)!,%/(*)!5)!W=P<WJP!4/U4)#8!!

b+/!5)%6+'+!5)!')$(!""3!$+*!/+!*%7)(#)!-.+!+&$(#+,%4(!$*)4%3!/%!0%&+!5)!)$+*0)/'*%2)(#+!&)!$+*5+!0*+:1+#'+4+#'+G!$+*!5)!$)F3!)/!5)%6+')-(!5)!')$(!""!0*+:1+#'+4+#'+!.%!&16)'(!%/'*)!5%##)!-.+!7/)!.%##(!7)>!*)5(''(!/%!01#2)(#%/)'>!*+#%/+!Y)$+*'+#&)(#+!5)!/1#7%!5%'%3!(6+&)'>3!014(!5)!&)7%*+''%Z3!$+*!-1)!)/!*+#+!0)/'*%!7)>!-(#!/%!01#2)(#+!*+&)51%!%/!4(4+#'(!5+//B)#&(*7+#2%!5+/!5)%6+'+3!$+*!-1)!)$+*0)/'*%#5(!*)+&-+!%5!%,+*+!iP!4/U4)#!5)!-*+%')#)#+!-/+%*%#-+!)#,+-+!-.+!)/!,%/(*+!5)!;P!4/U4)#!-.+!%,*+66+!&+#2%!)$+*0)/'*%2)(#+8!!

EB)$+*0)/'*%2)(#+!.%!5),+*&+!-%1&+G!

< EB)$+*7/)-+4)%!%14+#'%!)#5)*+''%4+#'+!/%!$*+&&)(#+!)5*(&'%')-%!#+)!-%$)//%*)!7/(4+*1/%*)!)#!:1%#'(!0(*2%!%!/),+//(!'161/%*+!)/!*)%&&(*6)4+#'(!5+/!&(5)(!Y%--($$)%'(!%/!*)%&&(*6)4+#'(!5+/!7/1-(&)(Z8!

Page 22: sbobinature nefro_0 - SkyDrive

!

< EB)$+*7/)-+4)%3!)#(/'*+3!'*%4)'+!5),+*&)!4+--%#)&4)!/(-%/)!Y&%'-"2'$*()3(%%()6,$#('*(G)"##'7"2'$*()3(%%")!b;G)"1/(*#$)3(%%")6,$312'$*()3')/"#,'-()(c#,"-(%%1%",(G)"%#(,"2'$*()3(%%")7'")3(')6$%'$%'Z!5+'+*4)#%!1#!5%##(!%/!$(5(-)'%3!$*(,(-%#5(!/%!5+$/+2)(#+!5+/!$((/!5)!:1+&'+!-+//1/+8!E%!5+$/+2)(#+!5+/!$((/!5)!$(5(-)')!5+'+*4)#%!/B)$+*%''),)'>!5)!:1+//)!*)4%#+#')3!%!&1%!,(/'%!-%1&%!5)!)$+*0)/'*%2)(#+8!

< "/!5%##(!7"0-$%",(!)#!-(*&(!5)!5)%6+'+!0%,(*)&-+!/B)#&(*7+#2%!5+//B)$+*'+#&)(#+3!&($*%''1''(!#+/!5)%6+'+!5)!')$(!""!-.+!&)!$*+&+#'%!-(#!)#&1/)#(<*+&)&'+#2%!+5!)$+*)#&1/)#+4)%G!)#!:1+&'(!-%&(!&)!.%!!/B%2)(#+!5+//B)#&1/)#%!-(4+!0%''(*+!5)!-*+&-)'%!$+*!/+!-+//1/+!41&-(/%*)!/)&-+!5+//+!%*'+*)(/+!5)!*+&)&'+#2%3!-(#!-(#&+71+#'+!)$+*'+#&)(#+8!EB)$+*'+#&)(#+3!%!/),+//(!*+#%/+3!5+'+*4)#%!%14+#'(!5+//%!$*+&&)(#+!)5*(&'%')-%!%!/),+//(!5+)!-%$)//%*)!7/(4+*1/%*)!+!3!:1)#5)3!)$+*0)/'*%2)(#+8!!

Ipertensione glomerulare Nel diabetico si verifica, fin dall’inizio della malattia, prima che insorga la

microalbuminuria, un aumento del GFR. Il fenomeno, che si associa ad ipertrofia dei glomeruli ed aumento del volume dei reni, è più evidente nel diabete tipo 1.

L’eccesso di glucosio filtrato a causa dell’iperglicemia viene riassorbito nel tubulo prossimale dal sistema di cotrasporto sodio-glucosio. Questo fenomeno ha due conseguenze

1)  L’accumulo di sodio e quindi di acqua espande la volemia e provoca la stimolazione dei recettori di stiramento atriale e quindi la secrezione cardiaca del peptide natriuretico atriale (ANP) che essendo un potente vasodilatatore provoca la vasodilatazione dell’arteriola afferente e quindi l’aumento della pressione glomerulare e del GFR

2)  La ridotta quantità di sodio che raggiunge la macula densa in conseguenza dell’eccessivo riassorbimento prossimale modifica il feedback tubulo-glomerulare, attivando meccanismi che portano alla vasodilatazione dell’arteriola afferente ed alla vasocostrizione dell’arteriola efferente.

L’ipertensione glomerulare è fra i principali determinanti del danno a carico della membrana basale glomerulare e quindi dell’insorgenza della nefropatia diabetica

Page 23: sbobinature nefro_0 - SkyDrive

< _+$(&)2)(#+!5+7/)!M^a!#+//%!4+46*%#%!6%&%/+!7/(4+*1/%*+!+!-(#&+71+#'+!*+%2)(#+!')&&1'%/+!+!%14+#'(!5+//%!5+$(&)2)(#+!5)!4%'*)-+8!

\(41#:1+!&)%3!/%!$%'(7+#+&)!5+//%!#+0*($%')%!5)%6+')-%!?!%#-(*%!/%*7%4+#'+!&-(#(&-)1'%8!

!

!

"44+5)%'%4+#'+!&1--+&&),%!%//%!0%&+!5+//B)$+*0)/'*%2)(#+!?!/%!-(4$%*&%!5+/!&+7#(!5)&')#'),(!5+//%!#+0*($%')%!5)%6+')-%G!%")/'-,$"%C1/'*1,'"9)"#)2)%/4+#'+!/%!4)-*(%/614)#1*)%!?!)#'+*4)''+#'+3!$+*!$()!5),+#'%*+!$+*&)&'+#'+!+!)#7*%,+&-+#'+8!O)!'*%''%!)#0%'')!5)!1#!3"**$)6,$&,(00'7$)d)-"10"#$)3"%%5'6(,&%'-(/'")L)-.()'*#(,(00")#1##')')*(+,$*'9)"!#+0*(#)3!$(-(!%!$(-(3!,%##(!)#-(#'*(!%//%!6(,3'#")3(')6$3$-'#'!D!:1+&'(!%--%5+!%5!1#!*)'4(!+&'*+4%4+#'+!/+#'(3!%--(4$%7#%'(!5%!1#!*)%/2(!$*(7*+&&),(!5+//%!$*('+)#1*)%3!-.+!$1N!&1$+*%*+!)!K!7*%44)!+!*%77)1#7+*+!/),+//)!5%!,+*%!+!$*($*)%!&)#5*(4+!#+0*(&)-%!Y*%*(Z8!!

!

Controllo glicemico Il controllo intensivo della glicemia, se realizzato

prima dell’insorgenza di danni terminali irrever-sibili a carico degli organi bersaglio, riduce l’incidenza delle complicanze macro- e micro-angiopatiche del diabetico.

Dal punto di vista renale, questo approccio si è dimostrato valido in tutti i pazienti ad eccezione di quelli con proteinuria conclamata, in cui il controllo rigoroso della pressione con un bloccante del sistema renina-angiotensina sembra essere più importante.

Page 24: sbobinature nefro_0 - SkyDrive

O'%5)!5+//%!#+0*($%')%!5)%6+')-%!

!

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sKPP!47UIQ.Z!&+7#%/%!/B%,,+#'(!5+//%!+&$%#&)(#+!4+&%#7)%/+!4%&&),%8!M//(!&'%5)(!5)!7/(4+*1/(&-/+*(&)!#(51/%*+!5)!n)44+&')+/<t)/&(#!%66)%4(!$*('+)#1*)%!)4$(*'%#'+!+5!)#&100)-)+#2%!*+#%/+8!!

!

Alterazioni morfologiche 1. Aumento di volume dei reni per ipertrofia dei tubuli, aumento della componente interstiziale, aumento del volume dei glomeruli per aumento della lunghezza e del diametro dei capillari 2.  Ispessimento della membrana basale glomerulare e tubulare 3. Espansione mesangiale a) diffusa b) nodulare (Kimmelstiel – Wilson) 4. Sclerosi (obsolescenza) glomerulare 5. Ialinosi dell’arteriola afferente ed efferente 6. Depositi lineari di IgG nella MBG 7. Degenerazione – atrofia tubulare e fibrosi interstiziale

Page 25: sbobinature nefro_0 - SkyDrive

O'(*)%!#%'1*%/+!

"/!&+7#(!$)F!$*+-(-+!5+//%!#+0*($%')%!5)%6+')-%!?!/%!-(4$%*&%!5)!4)-*(%/614)#1*)%!Ys!KP!47U5)+!(!IP!u7U4)#!(!KP!u7U47!-*+%')#)#%Z8!_%')!*+-+#')!)#5)-%#(!-.+!)/!WSR!-)*-%!5+)!$%2)+#')!#(*4(%/614)#1*)-)!-(#!5)%6+'+!')$(!W!5%!%/4+#(!=!%##)!&,)/1$$%#(!4)-*(%/614)#1*)%!Y#+0*($%')%!5)%6+')-%!)#-)$)+#'+Z8!EBJSR!5+)!5)%6+')-)!')$(!W!-(#!4)-*(%/614)#1*)%!$+*&)&'+#'+!#(#!'*%''%')!$*+&+#'%!1#!)#-*+4+#'(!5+//B+&-*+2)(#+!1*)#%*)%!5)!%/614)#%!%5!1#%!,+/(-)'>!5)!-)*-%!)/!WP<IPR!%//B%##(!0)#(!%!*%77)1#7+*+!/(!&'%5)(!5)!#+0*($%')%!-(#-/%4%'%3!-(#!$*('+)#1*)%!-/)#)-%4+#'+!+,)5+#'+!Y(,,+*(!%/614)#1*)%!s!KPP!47U5)+Z!)#!WP<WS!%##)8!^/)!%/'*)!$%2)+#')!$(&&(#(!*)4%#+*+!&'%2)(#%*)!(!*)'(*#%*+!#(*4(%/614)#1*)-)!Y%#-.+!$+*!+00+''(!5+//%!'+*%$)%Z8!`%77)1#'(!/(!&'%5)(!5)!#+0*($%')%!-(#-/%4%'%3!)/!$%2)+#'+!5),)+#+!)$+*'+&(!+3!&+#2%!)#'+*,+#')!&$+-)0)-)3!$*+&+#'%!1#%!7*%51%/+!*)512)(#+!5+/!^k`3!%5!1#%!,+/(-)'>!4(/'(!,%*)%6)/+!5%!)#5),)51(!%5!)#5),)51(!YIDIP!4/U4)#8%##(ZC!)/!SPR!5+)!5)%6+')-)!')$(!W!-(#!#+0*($%')%!-(#-/%4%'%!*%77)1#7+!/BaO`_!+#'*(!WP!%##)!+!$)F!5+/!=SR!+#'*(!IP!%##)8!L1%#5(!1#!$%2)+#'+!-(#!5)%6+'+!5)!')$(!"!&,)/1$$%!/%!#+0*($%')%!5)%6+')-%3!a1"0')0(/6,().")"*-.()%"),(#'*$6"#'"9!

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

"#)2)%/4+#'+!/%!4)-*(%/614)#1*)%!?!)#'+*4)''+#'+3!-(/!'+4$(!'+#5+!%!5),+#'%*+!$+*&)&'+#'+8!!

b+/!5)%6+'+!')$(!I!/%!&'(*)%!#%'1*%/+!5+//%!#+0*($%')%!?!%&&%)!&)4)/+8!V1''%,)%!4(/')!$%2)+#')!.%##(!4)-*(%/614)#1*)%!(!#+0*($%')%!-(#-/%4%'%!0)#!5%/!4(4+#'(!5+//%!5)%7#(&)!5)!5)%6+'+!')$(!I!(!5($(!$(-(!'+4$(3!$()-.[!)#!*+%/'>!)/!5)%6+'+!?!&$+&&(!$*+&+#'+!5%!4(/')!%##)!+5!%#-.+!$+*-.[!)#!:1+&')!$%2)+#')!/%!4)-*(%/614)#1*)%!$1N!+&&+*+!5(,1'%!%5!%/'*+!-%1&+8!b+)!5)%6+')-)!5)!')$(!""3!)#!7+#+*+3!:1%#5(!&)!&,)/1$$%!/%!$*('+)#1*)%!-/)#)-%4+#'+!+,)5+#'+!-B?!7)>!1#%!&)'1%2)(#+!5)!)#&100)-)+#2%!*+#%/+!-*(#)-%8!O+#2%!'+*%$)%!&$+-)0)-%3!)/!IPDQPR!5+)!5)%6+')-)!')$(!I!-(#!4)-*(%/614)#1*)%!&,)/1$$%!1#%!#+0*($%')%!-(#-/%4%'%3!4%!#+)!IP!%##)!&1--+&&),)!&(/(!)/!IPR!-)*-%!5)!:1+&')!$%2)+#')!*%77)1#7+!/BaO`_8!_%/!4(4+#'(!)#!-1)!)/!^k`!-(4)#-)%!%!*)51*&)3!/%!,+/(-)'>!5)!*)512)(#+!?!%/'%4+#'+!,%*)%6)/+!5%!1#!)#5),)51(!%//B%/'*(3!4%!#+/!-(4$/+&&(!/%!$*(7*+&&)(#+!#(#!5)00+*)&-+!&(&'%#2)%/4+#'+!5%!:1+//%!5+)!$%2)+#')!-(#!5)%6+'+!')$(!W8!!

EB+/+,%'%!4(*'%/)'>!\h!#+)!$%2)+#')!-(#!5)%6+'+!')$(!I!0%!&)!-.+!4(/')!5)%6+')-)!-(#!#+0*($%')%!-(#-/%4%'%!#(#!*%77)1#7(#(!/BaO`_8!H+*%/'*(3!)/!-(#')#1(!4)7/)(*%4+#'(!5+//%!'+*%$)%!Y0%*4%-(/(7)-%!+!#(#Z!5+//+!4%/%'')+!\h!0%*>!&)!-.+!)#!01'1*(!1#!#14+*(!&+4$*+!$)F!+/+,%'(!5)!5)%6+')-)!')$(!I!,),*%##(!%66%&'%#2%!5%!$*(7*+5)*+!0)#(!%//BaO`_8!9/'*+!%5!+&&+*+!/%!$*)4%!4%#)0+&'%2)(#+!5+//%!#+0*($%')%!5)%6+')-%3!#+)!5)%6+')-)!')$(!W!+!')$(!I!/%!4)-*(%/614)#1*)%!&)!%&&(-)%!%5!1#!#+''(!%14+#'(!5+/!*)&-.)(!5)!4(*6)/)'>!+!4(*'%/)'>!\h8!H+*'%#'(3!)/!*)/)+,(!5)!4)-*(%/614)#1*)%!?!1#%!$*+-)&%!)#5)-%2)(#+!%!*)-+*-%*+!%--1*%'%4+#'+!'1'')!7/)!%/'*)!0%''(*)!5)!*)&-.)(!\h!+!%5!%!4+''+*+!)#!%''(!4)&1*+!%77*+&&),+!$+*!*)51*/)!Y'*%''%*+!/%!5)&/)$)5+4)%!+!/B)$+*'+#&)(#+3!*%--(4%#5%*+!/B%''),)'>!0)&)-%3!%6(/)*+!)/!014(3!+--8Z8!M!:1+&'(!$*($(&)'(3!,)!&(#(!5%')!-.+!&177+*)&-(#(!-.+!/%!*)512)(#+!5+/!-(/+&'+*(/(!Y(!-(41#:1+!)/!'*%''%4+#'(!-(#!&'%')#+Z!$('*+66+!5+'+*4)#%*+!%#-.+!1#%!*)512)(#+!5+//%!$*('+)#1*)%8!!

!

Page 26: sbobinature nefro_0 - SkyDrive

X%#%7+4+#'!!

"/!$*)4(!%&$+''(!0(#5%4+#'%/+!?!)/!-$*#,$%%$)&%'-(/'-$)0-,16$%$0$3!4)&1*%!+00)-%-+!#+/!*)51**+!%/!4)#)4(!/%!$(&&)6)/)'>!5)!)#&(*7+#2%!+!$*(7*+&&)(#+!5+//%!#+0*($%')%8!"/!-(#'*(//(!7/)-+4)-(!&)!4(#)'(*%!%''*%,+*&(!)/!'+&'!5+//B+4(7/(6)#%!7/)-%'%3!-.+!5+,+!+&&+*+!)#0+*)(*+!%/!=R8!

"#!&+-(#5(!/1(7(!5(66)%4(!-$*#,$%%",()%5'6(,#(*0'$*()",#(,'$0"3!-.+!#+/!5)%6+')-(!5)!')$(!"!?!:1%&)!&+4$*+!&+-(#5%*)%!%/!5%##(!*+#%/+!Y%''),%2)(#+!5+/!&)&'+4%!*+#)#%<%#7)('+#&),%Z3!4+#'*+!#+/!5)%6+')-(!5)!')$(!""!?!7+#+*%/4+#'+!1#%!-(#5)2)(#+!$*++&)&'+#'+8!!b+/!5)%6+'+!')$(!W3!/B)$+*'+#&)(#+!?!5(,1'%!)#!7+#+*+!%/!5%##(!*+#%/+!+!&)!4%#)0+&'%!:1%#5(!-(4$%*+!/%!4)-*(%/614)#1*)%!(!$(-(!5($(8!!b+/!5)%6+'+!')$(!I3!/B)$+*'+#&)(#+!?!7)>!$*+&+#'+!%/!4(4+#'(!5+//%!5)%7#(&)!)#!-)*-%!WUK!5+)!$%2)+#')8!E%!-(+&)&'+#2%3!%&&%)!0*+:1+#'+3!5)!)$+*'+#&)(#+3!%/')!/),+//)!5)!-(/+&'+*(/(!E_E!+!'*)7/)-+*)5)!Y4+#'*+!)/!-(/+&'+*(/(!lE_!?!)#,+-+!*)5(''(Z3!(6+&)'>!+!+/+,%'(!*)&-.)(!5)!4%/%'')+!\h!&177+*)&-+!-.+!'1''+!:1+&'+!%/'+*%2)(#)!$(&&%#(!+&&+*+!/%!-(#&+71+#2%!5+//(!&'+&&(!4+--%#)&4(!$%'(7+#+')-(3!,+*(&)4)/4+#'+!5+//B)#&1/)#(*+&)&'+#2%8!L1+&'(!-(4$/+&&(!5)!%/'+*%2)(#)!?!#('(!-(4+!@&)#5*(4+!4+'%6(/)-%A8!!

b+/!5)%6+'+!')$(!I!/B)$+*'+#&)(#+!$1N!+&&+*+!5(,1'%!%//%!-(#'+4$(*%#+%!$*+&+#2%!5+//B)$+*'+#&)(#+!+&&+#2)%/+3!%//%!#+0*($%')%!5)%6+')-%!(,,+*(!%5!%/'*+!-%1&+!5)!)$+*'+#&)(#+!&+-(#5%*)%3!*+#%/)!Y)$+*'+#&)(#+!#+0*(,%&-(/%*+!(!#+0*($%*+#-.)4%/+Z!+!#(#8!EB)$+*'+#&)(#+!&)&'(/)-%!)&(/%'%!?!5(,1'%!%//%!$+*5)'%!5)!+/%&')-)'>!5+)!7*(&&)!,%&)!%*'+*)(&)!Y%*'+*)(&-/+*(&)Z8!

"#!7+#+*%/+3!/B)$+*'+#&)(#+!5+/!$%2)+#'+!-(#!5)%6+'+!&)%!5)!')$(!W!-.+!5)!')$(!I!&)!%&&(-)%!%5!1#!%14+#'(!5+/!,(/14+!$/%&4%')-(!+!5+//+!*+&)&'+#2+!$+*)0+*)-.+3!%!6%&&)!/),+//)!5)!*+#)#%!+5!?!@&(5)(<5)$+#5+#'+A!

!"/!,%/(*+!$*+&&(*)(!5+&)5+*%6)/+!?!'*#$,*$)")>D@Ee@9)<()'%)6"2'(*#().")&':)6,$#('*1,'"G)0')3$7,(CC()#(*#",()3'),"&&'1*&(,()')>A?Ef?9)q)&(7#%!+,)'%*+3!(,,)%4+#'+3!5)!&-+#5+*+!&(''(!)!WWP!5)!4%&&)4%!#+//+!$+*&(#+!%#2)%#+8!

_%/!$1#'(!5)!,)&'%!0%*4%-(/(7)-(3!)!0%*4%-)!5)!&-+/'%!&(#(!(,,)%4+#'+!)!&(/)')!S;4LR)()0",#"*'-'9!L1+&'(3!$+*-.[!%7)&-(#(!-(4+!#+0*($*('+''(*)!+!-(4+!%#')<)$+*'+#&),)8!O+!%#-.+!)/!$%2)+#'+!#(#!?!)$+*'+&(!&)!1')/)22%#(!-(41#:1+8!X(#)'(*%*+!$+*)(5)-%4+#'+!-*+%')#)#%!+5!+/+''*(/)')!$+*!$*+#5+*+!)#!'+4$(!+,+#'1%/)!)$+*]%/)+4)+!(!)#&100)-)+#2%!*+#%/+!%-1'%8!EB)$+*]%/)+4)%!$1N!+&&+*+!$*+-)$)'%'%!5%//B%&&(-)%2)(#+!5)!%/'*)!0%*4%-)!)$+*]%/)+4)22%#')3!-(4+!kMbO!(!)#)6)'(*)!5+//%!-%/-)#+1*)#%8!V*%!/B%/'*(3!1#!*+-+#'+!&'15)(!&1/!barX!5)4(&'*%!-(4+!7/)!M\a<"!+!)!&%*'%#)!D!&+!1&%')!-(**+''%4+#'+!D!&)%#(!(*4%)!-(#&)5+*%6)/)!-(4+!0%*4%-)!5)!&-+/'%!%#-.+!#+)!$%2)+#')!-(#!&'+#(&)!5+//B%*'+*)%!*+#%/+8!7/)!M\a<"!)#51-(#(!'(&&+3!&($*%''1''(!#+//+!5(##+G!)#!:1+&')!-%&)!?!$(&&)6)/+!$%&&%*+!%5!1#!&%*'%#)-(8!L1+&')!0%*4%-)3!)#(/'*+3!&(#(!-(#'*()#5)-%')!)#!7*%,)5%#2%3!+!:1+&'(!,%!&$)+7%'(!-.)%*%4+#'+!%//+!5(##+8!M\a<"!+!&%*'%#)!&(#(!+00)-%-)!#+//B)$+*'+#&)(#+!+3!&($*%''1''(3!&(#(!)#!7*%5(!5)!-(#'*%&'%*+!/%!$*('+)#1*)%8!

"!0%*4%-)!5)!&+-(#5%!&-+/'%3!5%!%77)1#7+*+3!&(#(!+,+#'1%/4+#'+!)!-%/-)(<%#'%7(#)&')!Y%4/(5)$)#%Z8!"#!'+*2%!&-+/'%3!&)!1&%#(!)!!<6/(--%#')!5)!#1(,%!7+#+*%2)(#+3!-.+!#(#!-%1&%#(!)$+*7/)-+4)%8!!

_5$C(0'#:)3(7()(00(,()-$,,(##"3!+!)/!5)4%7*)4+#'(!$1N!+&&+*+!5)!7*%#5+!6+#+0)-)(3!-(4+!$1*+!)/!'*%''%4+#'(!5)!+,+#'1%/)!5)&/)$)5+4)+!+!/B%66%#5(#(!5+/!014(!5)!&)7%*+''%8!q)&(7#+*+66+!+,)'%*+!)!kMbO3!/)4)'%#5(/)!%)!-%&)!5)!+00+''),%!#+-+&&)'>8!!

Page 27: sbobinature nefro_0 - SkyDrive

E%!3'(#")'6$6,$#('-"!?!1#!%&$+''(!)4$(*'%#'+3!&($*%''1''(!:1%#5(!)/!^k`!)#)2)%!%!5+-%5+*+!*%$)5%4+#'+G!%''+#2)(#+3!-(41#:1+3!%!#(#!5+'+*4)#%*+!-%*+#2+!%/)4+#'%*)!+--+&&),+!+!5+$+*)4+#'(!5+//+!4%&&+!41&-(/%*)8!!

V*%$)%#'(v!

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k`!j!IP!4/U4)#Z3!$*+0+*)6)/4+#'+!5%!5(#%'(*+!,),+#'+8!b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

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

Page 28: sbobinature nefro_0 - SkyDrive

^/(4+*1/(#+0*)')!

E+!7/(4+*1/(#+0*)')!*%$$*+&+#'%#(!1#(!5+)!-%$)'(/)!$)F!%4$)!5+//%!#+0*(/(7)%8!b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

!

!

T#%!$%'(/(7)%!7/(4+*1/%*+!$1N!)#'+*+&&%*+!

:1%/&)%&)! +/+4+#'(!

Glomerulo normale

Page 29: sbobinature nefro_0 - SkyDrive

5+//%!4+46*%#%!5)!0)/'*%2)(#+G!

< a#5('+/)(!5+/!-%$)//%*+!7/(4+*1/%*+!< H(5(-)'%!< X%'*)-+!+g'*%-+//1/%*+!+!&1+!$*('+)#+!

a&)&'(#(!$()!/+!-+//1/+!4+&%#7)%/)3!)4$(*'%#')!*+7(/%'(*)!$%*%-*)#)!+!0)&)-)!5+//+!01#2)(#)!7/(4+*1/%*)8!

V1''%,)%3!1#%!$%'(/(7)%!7/(4+*1/%*+!$1N!+&)'%*+!)#!)#&100)-)+#2%!*+#%/+!+#5<&'%7+!&(/'%#'(!&+!)#'+*+&&%!)/!$(5(-)'%3!/B1#)-%!-+//1/%!)#-%$%-+!5)!*+$/)-%*&)!+!:1)#5)!5)!*)7+#+*%*&)8!O+!)/!$(5(-)'%!0(&&+!)#!7*%5(!5)!*+$/)-%*&)3!)#0%'')3!/%!6%**)+*%!7/(4+*1/%*+!&%*+66+!-(#')#1%4+#'+!&(77+''%!%!4(5)0)-%2)(#)!&'*1''1*%/)!+!#(#!$('*+66+!%&&(/,+*+!%//%!&1%!01#2)(#+!5)!0)/'*%2)(#+8!\(&e3!)/!$(5(-)'%!?!1#%!-+//1/%!)#-%$%-+!5)!5),)5+*&)G!&+!:1+&'(!?!$(&)'),(!$+*!/%!01#2)(#+!5)!0)/'*%2)(#+3!?!'1''%,)%!1#!0%''(!-.+!*+#5+!/B)#'+*(!&)&'+4%!5)$+#5+#'+!5%//%!&($*%,,),+#2%!5+)!$(5(-)')8!b+/!4(5+//(!41*)#(!?!&'%'(!5)4(&'*%'(!-.+!/%!4(*'+!5)!1#%!:1('%!5)!$(5(-)')!)#0+*)(*+!%/!IPR!#(#!-%1&%!5%##(C!'*%!IP<KPR!&)!(&&+*,%!1#B+&$%#&)(#+!4+&%#7)%/+C!-(#!/%!4(*'+!5+/!QPR!-)*-%!5+)!$(5(-)')!&)!5+'+*4)#%!1#%!7/(4+*1/(&-/+*(&)!0(-%/+!&+74+#'%/+!Y0(-%/+!m!#(#!'1'')!)!7/(4+*1/)!&(#(!-()#,(/')C!&+74+#'%/+!m!&(/(!)#!%/-1#+!$%*')!5+/!7/(4+*1/(Z8!L1%#5(!41(*+!)/!SS<;PR!5+)!$(5(-)')!&)!5+'+*4)#%!1#%!7/(4+*1/(&-/+*(&)!7/(6%/+8!L1)#5)3!%")6,$&*$0')3(%%()/"%"##'()&%$/(,1%",')3'6(*3()3"%%")a1$#")3')6$3$-'#')-.()7(*&$*$)3"**(&&'"#'9)

"#!+00+'')3!&)!?!,)&'(!-.+!%/-1#+!7/(4+*1/(#+0*)')!*)'+#1'+!1#!'+4$(!&1!6%&+!)#0)%44%'(*)%3!4%!#(#!*+&$(#&),+!%!&'+*()5)!+5!)441#(&($$*+&&(*)!D!')$)-.+!5+)!6%46)#)!D!&(#(!)#!*+%/'>!$%'(/(7)+!-%1&%'+!5%//%!41'%2)(#+!5)!%/-1#)!7+#)!-()#,(/')!#+//B%&&+46/%4+#'(!5+/!-)'(&-.+/+'*(!$(5(-)'%*)(8!

V1''%,)%!?!&'%'(!%#-.+!&-($+*'(!-.+!)/!#+0*(#+!$(&&)+5+!1#!-(4$%*')4+#'(!&'%4)#%/+!D!/(-%/)22%'(!%!/),+//(!5+/!$(/(!1*)#%*)(!5+//%!-%$&1/%!5)!q(f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

\/%&&)0)-%2)(#+!

E+!$%'(/(7)+!7/(4+*1/%*)!$(&&(#(!+&&+*+!5)!')$(!'*+'"//"#$,'$)Y&%$/(,1%$*(+,'#'Z!($$1*+!$(&&(#(!+&&+*+!5)!')$(!#(#!$*($*)%4+#'+!)#0)%44%'(*)(!Y&%$/(,1%$6"#'(3!$*)-)%$%/4+#'+!/%!7/(4+*1/($%')%!5)%6+')-%!+!/+!7/(4+*1/($%')+!5%!5+$(&)2)(#+!5)!$%*%$*('+)#+Z8!"#!*+%/'>3!$+*N3!4(/'+!7/(4+*1/(#+0*)')!&(#(!$%'(/(7)+!#+//+!:1%/)!#(#!+&)&'+!1#%!,+*%!+!$*($*)%!-%1&%!)441#(/(7)-%G!:1+&'%!5)&')#2)(#+3!%#-.+!&+!1')/+!5%/!$1#'(!5)!,)&'%!5)5%'')-(3!?!:1)#5)!$(-(!,+*)')+*%8!!

\/%&&)-%4+#'+3!/+!4%/%'')+!7/(4+*1/%*)!&(#(!&'%'+!5)&')#'+!)#!6,'/'#'7()+!0(-$*3",'(G!&+-(#5%*)+!&(#(!/+!0(*4+!-.+!-(4$%)(#(!#+/!-(#'+&'(!5)!1#%!$%'(/(7)%!&)&'+4)-%3!4+#'*+!:1+//+!$*)4)'),+!&(#(!)#!7*%#!$%*'+!)5)($%')-.+8!!

a&)&'(#(!$()!1#%!&+*)+!5)!4%/%'')+!7/(4+*1/%*)!(,(3'#",'(3!*%*+8!T#!'+4$(!

Primitive

•  Nefropatia ad IgA •  GN membranosa •  Glomerulosclerosi focale e segmentale •  GN Proliferativa mesangiale •  GN Post-infettive •  GN Membranoproliferativa •  Nefropatia ad IgM •  Malattia a lesioni minime •  GN a semilune

Secondarie

• Malattie sistemiche a patogenesi autoimmune nefrite lupica vasculiti Disgammaglobulinemie Amiloidosi renale Crioglobulinemia mista essenziale Mieloma

Glomerulonefrite

Ereditarie

• Sindrome di Alport • Malattia di Anderson-Fabry • Malattia a membrane sottili • Deficit di Lecitina-Colesterolo acil-transferasi • Glomerulopatia da lipoproteine • Cistinosi • Sindrome nefrosica finlandese • Sclerosi mesangiale diffusa

Page 30: sbobinature nefro_0 - SkyDrive

:1+&'+!$%'(/(7)+!-%1&%,%#(!/%!4(*'+!5+/!$%2)+#'+!)#!7)(,%#)&&)4%!+'>G!(77)!-.+!&)%4(!)#!7*%5(!5)!0%*!&($*%,,),+*+!:1+&')!6%46)#)!0)#(!%//B+'>!%51/'%3!-(#(&-)%4(!4(/'(!4+7/)(!/(!&$+''*(!5+//+!-(4$/)-%')&&)4+!%#(4%/)+!7+#+')-.+!-.+!$(&&(#(!-%1&%*+!$%'(/(7)+!*+#%/)!$*)4)'),+8!

V*%!/+!7/(4+*1/(#+0*)')!$*)4)'),+3!/%!#+0*($%')%!%5!"7M!?!&)-1*%4+#'+!/%!$)F!0*+:1+#'+3!)#'+*+&&%#5(!$*(6%6)/4+#'+!/BWR!5+//%!$($(/%2)(#+3!&($*%''1''(!#+//+!$($(/%2)(#)!%&)%')-.+3!5(,+!.%!1#B)#-)5+#2%!5%,,+*(!+/+,%'%8!d!1#%!$%'(/(7)%!-.+!$(*'%!-(#!&[!%/'+*%2)(#)!4)#)4+!)#!'+*4)#)!5)!$*('+)#1*)%!+!4)-*(+4%'1*)%3!+!)!$%2)+#')!&(#(!%&&(/1'%4+#'+!%&)#'(4%')-)3!$+*'%#'(!#(#!,+#),%!5%'%!)4$(*'%#2%!%!'%/)!*)&-(#'*)8!d!')$)-%4+#'+!1#%!$%'(/(7)%!5+/!7)(,%#+8!!

!

!

V*%!/+!7/(4+*1/(#+0*)')!&+-(#5%*)+!/%!$)F!)4$(*'%#'+!?!&)-1*%4+#'+!/%!#+0*)'+!/1$)-%3!&+71)'%!5%//+!%/'*+!,%&-1/)')!%1'()441#)8!h)!&(#(!$()!/+!,%*)+!5)&7%44%7/(61/)#+4)+8!

!

!

!

!

_%/!$1#'(!5)!,)&'%!5+/!:1%5*(!'0#$6"#$%$&'-$3!/+!7/(4+*1/(#+0*)')!&)!5),)5(#(!)#!51+!7*%#5)!7*1$$)G!/+!0(*4+!6,$%'+(,"#'7()+!/+!0(*4+!*$*)6,$%'+(,"#'7(9)b+//+!0(*4+!$*(/)0+*%'),+3!%//B)#'+*#(!5+/!7/(4+*1/(!'*(,)%4(!-+//1/+!$*(/)0+*%#')3!-.+!$(&&(#(!+&&+*+!&(/(!/+!4+&%#7)%/)!(!/+!+#5('+/)%/)8!L1+&'(!?!4(/'(!)4$(*'%#'+3!$+*-.[!:1%#5(!%66)%4(!1#!:1%5*(!$*(/)0+*%'),(!7+#+*%/4+#'+!%66)%4(!1#!:1%5*(!5)!(/"#1,'"!+!6,$#('*1,'")0$##$)')D&EAB.9)E+!0(*4+!$*(/)0+*%'),+!&(#(!)#0%'')!:1%5*)!)#0)%44%'(*)!-(#!*)/%&-)(!5)!

Le cause principali di glomerulonefrite sono diverse in differenti gruppi d’età

La frequenza delle glomerulonefriti nell’anziano rispetto all’adulto è di 30.8 vs. 28.3 casi per milione. Le forme più frequenti sono le seguenti:

• GN Membranosa (13.4 vs.4.2 PMP)

• GN a semilune (3.1 vs.0.9 PMP)

• GN Membranoproliferativa (2.9 vs. 0.4 PMP)

• GN acuta post-streptococcica (0.9 vs. 0.4 PMP)

• Nefropatia ad IgA (18.8%)

• Malattia a lesioni minime (11.6%),

• Glomerulosclerosi focale e segmentale (8.5%), • GN proliferativa mesangiale (9.5%), • GN Membranoproliferativa (5.5%), • Nefrite lupica (5%)

L ’ i n c i d e n z a a n n u a l e d e l l e glomerulonefriti tra i bambini italiani è di 11.1 casi per milione.

Le forme più frequenti sono le seguenti:

Primitive

•  Nefropatia ad IgA •  GN membranosa •  Glomerulosclerosi focale e segmentale •  GN Proliferativa mesangiale •  GN Post-infettive •  GN Membranoproliferativa •  Nefropatia ad IgM •  Malattia a lesioni minime •  GN a semilune

Secondarie

• Malattie sistemiche a patogenesi autoimmune nefrite lupica vasculiti Disgammaglobulinemie Amiloidosi renale Crioglobulinemia mista essenziale Mieloma

Glomerulonefrite

Ereditarie

• Sindrome di Alport • Malattia di Anderson-Fabry • Malattia a membrane sottili • Deficit di Lecitina-Colesterolo acil-transferasi • Glomerulopatia da lipoproteine • Cistinosi • Sindrome nefrosica finlandese • Sclerosi mesangiale diffusa

Primitive

•  Nefropatia ad IgA •  GN membranosa •  Glomerulosclerosi focale e segmentale •  GN Proliferativa mesangiale •  GN Post-infettive •  GN Membranoproliferativa •  Nefropatia ad IgM •  Malattia a lesioni minime •  GN a semilune

Secondarie

• Malattie sistemiche a patogenesi autoimmune nefrite lupica vasculiti Disgammaglobulinemie Amiloidosi renale Crioglobulinemia mista essenziale Mieloma

Glomerulonefrite

Ereditarie

• Sindrome di Alport • Malattia di Anderson-Fabry • Malattia a membrane sottili • Deficit di Lecitina-Colesterolo acil-transferasi • Glomerulopatia da lipoproteine • Cistinosi • Sindrome nefrosica finlandese • Sclerosi mesangiale diffusa

Page 31: sbobinature nefro_0 - SkyDrive

-)'(-.)#+!-.+!-%1&%#(!1#%!$+*4+%6)/)22%2)(#+!5+)!-%$)//%*)!+!/%!$*(/)0+*%2)(#+!-+//1/%*+8!L1)#5)3!1#!$%2)+#'+!-(#!4)-*(<!(!4%-*(+4%'1*)%!+!1#%!$*('+)#1*)%!4(5+&'%!:1%&)!&)-1*%4+#'+!&%*>!%00+''(!5%!1#%!0(*4%!$*(/)0+*%'),%8!h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

!

!

O)#5*(4)!-/)#)-.+!%&&(-)%'+!%!7/(4+*1/(#+0*)')!

O(&'%#2)%/4+#'+3!&)!.%##(!"%#(,"2'$*')3(%)0(3'/(*#$)1,'*",'$Q!5(66)%4(!&(&$+''%*+!1#%!7/(4+*1/(#+0*)'+!:1%#5(!*)&-(#'*)%4(!%/'+*%2)(#)!5+/!&+5)4+#'(3!+!5(66)%4(!&16)'(!%#5%*+!%!-(#'*(//%*+!)/!&+5)4+#'(!:1%#5(!&(&$+'')%4(!1#%!7/(4+*1/(#+0*)'+8!

M/'+*%2)(#)!5+/!&+5)4+#'(!#(#!&)7#)0)-%!%&&(/1'%4+#'+!&)#5*(4+!#+0*(&)-%!(!&)#5*(4+!#+0*)')-%G!(,,)%4+#'+!:1+&')!:1%5*)!&)#5*(4)-)!$%*')-(/%*)!6$00$*$)-(4$%*)*+!)#!-(*&(!5)!7/(4+*1/(#+0*)'+3!4%!#(*4%/4+#'+!#(#!&(#(!$*+&+#')8!V)$)-%4+#'+!)!$%2)+#')!.%##(!&+4$/)-+4+#'+!+4%'1*)%!4)-*(&-($)-%!+!$*('+)#1*)%8!E+!4%#)0+&'%2)(#)!-/)#)-.+3!:1)#5)3!*)&1/'%#(!5%G!

< 4/"#1,'")&%$/(,1%",()/"-,$0-$6'-")$)/'-,$0-$6'-")< !,$#('*1,'")&%$/(,1%",()< ;'%'*3,1,'")< U'312'$*()3(%%")+1*2'$*(),(*"%()

E%!'%6+//%!:1%!&(''(!*)$(*'%!/+!$*)#-)$%/)!0(*4+!5)!7/(4+*1/(#+0*)'+!-(#!/+!*)&$+''),+!4%#)0+&'%2)(#)!-/)#)-.+!$)F!0*+:1+#')8!"#!*(&&(!&(#(!)#5)-%'+!/+!0(*4+!#(#!$*(/)0+*%'),+8!

Page 32: sbobinature nefro_0 - SkyDrive

!

E%!^b!%!&+4)/1#+!?!1#!:1%5*(!-.+!0%!&'(*)%!%!&[!+!0*+:1+#'+4+#'+!&)!$*+&+#'%!-(#!1#%!&)#5*(4+!#+0*)')-%!+5!%#(4%/)+!1*)#%*)+!4%3!$+*!+&+4$)(3!*%*%4+#'+!&)!$*+&+#'%!-(#!+4%'1*)%!)&(/%'%8!L1)#5)3!:1+//(!-.+!-)!)#'+*+&&%!?!-.+!)/!:1%5*(!-/)#)-(!5+/!$%2)+#'+!?!7)>!%66%&'%#2%!&177+&'),(!5+/!')$(!&$+-)0)-(!5)!^b!)#!:1+&')(#+8!

"/!&$%3)0#"*3",3!$+*!/%!5)%7#(&)!5)!7/(4+*1/(#+0*)'+!?!(,,)%4+#'+!/%!C'$60'"),(*"%(9)E%!6)($&)%!*+#%/+!&)!+&+71+!#+)!&+71+#')!-%&)G!

< 81##')')-"0')3')0'*3,$/()*(+,$0'-"3!+--+''(!-.+!#+)!6%46)#)8!< F1"3,')-$/C'*"#')3')6,$#('*1,'")()/'-,$(/"#1,'"9!< !,$#('*1,'()016(,'$,')"3)>)&EAB.)!)#!$%2)+#')!%51/')8!< O"-,$(/"#1,'")'0$%"#"),'-$,,(*#(!

"#!-%&(!5)!+4%'1*)%!)&(/%'%3!)#,+-+3!&)!%&$+''%!D!%!4+#(!-.+!#(#!,)!&)%#(!*)-.)%4)!$%*')-(/%*)!%5!1#%!$%'(/(7)%!7+#+')-%!-.+!4%7%*)!-()#,(/7+!%/'*)!4+46*)!5+//%!0%4)7/)%8!E%!6)($&)%!*+#%/+!?!(77)!1#%!'+-#)-%!&)-1*%G!/B1#)-%!-(4$/)-%#2%!-.+!&)!$1N!*)&-(#'*%*+!-(#!1#%!-+*'%!0*+:1+#2%!?!1#%!4%-*(+4%'1*)%!#+//+!$*)4+!IQ!(*+!YWPR!5+)!-%&)Z8!\(4$/)-%#2+!$)F!7*%,)3!-(4+!0)&'(/+!M<h!+5!)$+*'+#&)(#+!&+-(#5%*)%!&)!,+5(#(!(*4%)!4(/'(!*%*%4+#'+8!a&)&'(#(!$()!-$*#,$'*3'-"2'$*')"00$%1#(Q)

< M#+4)%!7*%,+!< "$+*'+#&)(#+!4%/!-(#'*(//%'%!< H%2)+#')!(6+&)!< \(%71/($%')+!< k1#2)(#+!*+#%/+!5+'+*)(*%'%!< `+#+!$)--(/(!Y$+*-.[!)#5)-%'),(!5)!$%'(/(7)%!-*(#)-%!)**+,+*&)6)/+Z!< V14(*)!*+#%/)!Y*)&-.)(!5)!)#&++5)#7Z!< H%2)+#')!#(#!5)&$(&')!%!-(($+*%*+!< "#0+2)(#)!*+#%/)!(!$+*)*+#%/)!< h%&-1/)')!-(#!41/')$/)!%#+1*)&4)!)#'*%*+#%/)!

!

>9 `%$/(,1%$*(+,'#')*$*)6,$%'+(,"#'7()< `%$/(,1%$*(+,'#()/(/C,"*$0")< `%$/(,1%$*(+,'#()")%(0'$*')/'*'/()

Sindromi cliniche associate alle principali forme di glomerulonefrite

Sindrome nefrosica

Sindrome nefritica

Anomalie urinarie

Ematuria isolata

Malattia a lesioni minime +++++ - ++ -/+

GN membranosa ++++ + ++ -/+

GS focale e segmentale +++ + ++ -/+

Nefropatia ad IgA ++ +++ ++++ ++++

GN membranoproliferativa +++ +++ ++++ -/+

GN proliferativa endocapillare + ++++ ++++ ++

GN a semilune + ++++ ++++ -

Page 33: sbobinature nefro_0 - SkyDrive

< `%$/(,1%$0-%(,$0')+$-"%()0(&/(*#"%()

`%$/(,1%$*(+,'#()/(/C,"*$0")

a&(*5)&-+!:1%&)!&+4$*+!-(4+!1#%!&)#5*(4+!#+0*(&)-%3!(!-(41#:1+!-%1&%!1#%!$*('+)#1*)%!7*%,+8!H1N!+&&+*+!$*+&+#'+!+4%'1*)%3!4%!4%)!5)!7*%5(!)4$(*'%#'+G!1#B+4%'1*)%!&+*)%!-)!-(#&+#'+!7)>!5)!+&-/15+*+!/%!^b!4+46*%#(&%8!!

E%!^b!4+46*%#(&%!?!1#%!$%'(/(7)%!)441#(4+5)%'%!5(,1'%!%//%!3(6$0'2'$*()3')'//1*$-$/6%(00'!#+//%!4%'*)-+!+g'*%-+//1/%*+!5+//%!4+46*%#%!5)!0)/'*%2)(#+G!:1+&'(!?!-)N!-.+!,+5)%4(!%//%!6)($&)%!*+#%/+3!5+$(&)')!5)!4%'+*)%/+!$*('+)-(!+(&)#(0)/(!%/!5)!&(''(!5+)!$(5(-)')8!

H*(6%6)/4+#'+3!&)!'*%''%!5)!1#%!$%'(/(7)%!:1%&)!&+4$*+!&+-(#5%*)%G!!

< 45)1*")0'*3,$/()6","*($6%"0#'-")V)$)-%4+#'+!)#!-(*&(!5)!'14(*)!&(/)5)!Y-(/(#<*+''(3!$(/4(#+Z!)#!$%2)+#')!%#2)%#)8!

< O"%"##'()"1#$'//1*')E%!#+0*)'+!4+46*%#(&%!?!/%!-/%&&+!h!5+//%!#+0*)'+!/1$)-%8!

< R*+(2'$*')O($*%''1''(!+$%')'+!q3!&)0)/)5+3!4%/%*)%!5%!H8!4%/%*)%+8!!

< ^",/"-')H+#)-)//%4)#%3!&%/)!5B(*(3!-"6#$6,'%G)^S=<3!-.+!$*(6%6)/4+#'+!&(#(!1#%!5+//+!-%1&+!$*)#-)$%/)!5)!^b!4+46*%#(&%!Y7*(&&+!5(&)!$+*!'+4$)!$*(/1#7%')3!/%!$%'(/(7)%!*+-+5+!-(#!/%!&(&$+#&)(#+!5+//B1&(Z8!!

O)!?!,)&'(3!-(#!:1+&')!-*)'+*)3!-.+!-)*-%!)/!WSR!5+//+!^b!4+46*%#(&+!&(#(!,+*(&)4)/4+#'+!-%1&%'+!5%)!kMbO8!!a&)&'(#(!$()!:1+//+!+')-.+''%'+!-(4+!'3'$6"#'-.(3!%#-.+!&+!D!$*(6%6)/4+#'+!D!#(#!+&)&'(#(!0(*4+!*+%/4+#'+!)5)($%')-.+8!!"&'(/(7)%!!

!!!!

!

!

!

!

La glomerulonefrite membranosa è una malattia immunologica anticorpo-mediata nella quale gli immunocomplessi si localizzano sul versante sottoepiteliale del capillare glomerulare, tra la membrana basale ed il podocita.

•  Anticorpi si legano in situ ad antigeni esogeni cationici ed a basso peso molecolare previamente depositatisi sulla parete esterna della MBG

•  Immunocomplessi formatisi in circolo attraversano la MBG depositandosi sulla sua parete esterna.

•  Autoanticorpi si legano in situ a una componente costitutiva delle cellule epiteliali della parete capillare (es, la megalina) !

Glomerulonefrite membranosa

La glomerulonefrite membranosa è una malattia immunologica anticorpo-mediata nella quale gli immunocomplessi si localizzano sul versante sottoepiteliale del capillare glomerulare, tra la membrana basale ed il podocita.

•  Anticorpi si legano in situ ad antigeni esogeni cationici ed a basso peso molecolare previamente depositatisi sulla parete esterna della MBG

•  Immunocomplessi formatisi in circolo attraversano la MBG depositandosi sulla sua parete esterna.

•  Autoanticorpi si legano in situ a una componente costitutiva delle cellule epiteliali della parete capillare (es, la megalina)!

Glomerulonefrite membranosa

Nel primo stadio anche a maggior ingrandimento le pareti capillari

non presentano evidenti aspetti di ispessimento o evidenti depositi

sottoepiteliali.

Tuttavia, pur in assenza di evidenti depositi al microscopio ottico,

l'immuno-fluorescenza è caratterizzata da depositi

fluorescenti diffusi lungo la membrana basale, con aspetto

finemente granulare o simil-lineare.

Istologicamente si ha un ispessimento omogeneo e diffuso della membrana basale. A seconda del grado di ispessimento

si distinguono 4 stadi.

Page 34: sbobinature nefro_0 - SkyDrive

!

!

!

!

O1//%!6%&+!5+//B)&'(/(7)%!+!5+//B)&$+&&)4+#'(!5+//%!4+46*%#%!6%&%/+3!&)!5)&')#71(#(!:1%''*(!&'%5)!$*(7*+&&),)8!

!

_+-(*&(!

L)g*)#(,2$)3(')6"2'(*#')7")'*-$*#,$)"),(/'00'$*()06$*#"*(")#+/!7)*(!5)!1#!%##(U1#!%##(!+!4+22(C!:1+&'%!?!1#%!$*(,%!5+//%!&+-(#5%*)+'>!5+//%!4%/%'')%G!*)4(&&(!/(!&')4(/(!D!%#-.+!)#%,,+*')'%4+#'+!D!&+!#+!,%!%#-.+!/%!4%/%'')%8!

L)g*)#(,2$)3(')6"2'(*#')07'%166")1*)a1"3,$)-,$*'-$)3')*(+,$0')-.()*$*)6,$&,(3'0-()7(,0$)%5'*01++'-'(*2"),(*"%()#(,/'*"%(9)

L)g*)#(,2$)3(')6"2'(*#')7")'*-$*#,$)"3)'*01++'-'(*2"),(*"%()#(,/'*"%(9)

O)--(4+!1#!'+*2(!5+)!$%2)+#')!,%!)#!*+4)&&)(#+!&$(#'%#+%3!&)!'+#5+!%!#(#!'*%''%*+!&16)'(!/%!4%/%'')%3!$*($*)(!#+//B+,+#'1%/)'>!-.+!&)!'*%'')!5)!1#%!0(*4%!&+-(#5%*)%!/%!-1)!(*)7)#+!&)%!5%!*)-+*-%*+8!L1+//(!-.+!#(#!4%#-%3!$+*N3!?!/%!'+*%$)%!-(#!M\a<"!+!&%*'%#)3!4)*%'%!%!*)51**+!/%!$*('+)#1*)%8!O+!+#'*(!51+!%##)!#(#!&)!('')+#+!*+4)&&)(#+!Y(!)#!-%&(!5)!0(*4+!%77*+&&),+Z!&)!$1N!$+#&%*+!5)!'*%''%*+!)/!$%2)+#'+!-(#!&'+*()5)!+5!)441#(&($$*+&&(*)C!(77)!&)!1')/)22%!4(/'(!)/!*)'1g)4%6!YX%6V.+*%Z3!%#')-(*$(!4(#(-/(#%/+!%#')<\_IP!-.+!&)!&'%!*),+/%#5(!$)1''(&'(!+00)-%-+8!

!

O"%"##'")")%(0'$*')/'*'/()

M#-.+!:1+&'(!?!1#!:1%5*(!#(#!$*(/)0+*%'),(3!+!&)!,+5+!#+)!6%46)#)G!$1N!+&&+*+!%&&(-)%'%!%!/+1-+4)+!+!/)#0(4)!+!&)!$*+&+#'%!-(#!4%77)(*+!0*+:1+#2%!#+7/)!%'($)-)!)4$(*'%#')8!V)$)-%4+#'+3!)/!6%46)#(!&)!$*+&+#'%!7(#0)(3!+5+4%'(&(!+!,)+#+!*)-(,+*%'(8!_1*%#'+!:1+&'(!$*)4(!+$)&(5)(!#+0*(&)-(!%-1'(3!&$+&&(!,)+#+!)4$)+7%'%!1#%!'+*%$)%!+g!)1,%#')61&!-(#!1#(!&'+*()5+3!5($(5)-.[!)/!6%46)#(!,%!)#!*+4)&&)(#+8!H1*'*($$(3!$+*N3!&(/(!)/!IPR!

La colorazione argentica mette in risalto piccole estroflessioni nere (spikes) si proiettano all'esterno

della membrana basale assumendo il tipico aspetto di "denti di pettine".

Queste spicule sono separate dai depositi sottoepiteliali che non si

colorano all'argento e caratterizzano il II stadio.

Nel III stadio a forte ingrandimento è evidente il massivo

ispessimento delle pareti capillari, con la tendenza della membrana basale ad estendersi e ricoprire i

depositi facendoli apparire incapsulati ed inglobati.

Page 35: sbobinature nefro_0 - SkyDrive

5+)!6%46)#)!71%*)&-+G!)!*+&'%#')!%,*%##(!*+-)5),+8!M/-1#)!$%2)+#')3!5($(!1#!-+*'(!#14+*(!5)!*+-)5),+!D!&$+&&(!&-%'+#%'+!5%!+$)&(5)!)#0+''),)!<3!%#5*>!5+0)#)'),%4+#'+!)#!*+4)&&)(#+8!97#)!*+-)5),%!$1N!+&&+*+!'*%''%'%!+00)-%-+4+#'+!-(#!7/1-(-(*')-()5)3!5%!:1)!/B)5+%!'*%5)2)(#%/+!-.+!:1+&'%!0(*4%!5)!^b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a&)&'(#(!$()!)!$%2)+#')!0#(,$'3$L,(0'0#(*#'G!7+#+*%/4+#'+!/%!&'+*()5(<*+&)&'+#2%!&)!4%#)0+&'%!%5!)#)2)(!'+*%$)%3!4%!+&)&'(#(!%#-.+!-%&)!5)!&'+*()5(<*+&)&'+#2%!%-:1)&)'%!)#!-(*&(!5)!'+*%$)%8!"#!:1+&')!-%&)3!)/!SPR!5+)!6%46)#)!&(#(!)#!*+%/'>!%00+''!5%!1#%!6"#$%$&'")&(*(#'-"!-.+!-(/$)&-+!)/!*+#+8!k)#(*%!#+!&(#(!&'%'+!)5+#')0)-%'+!WI3!+5!?!$(&&)6)/+!-.+!%#-.+!)/!*+&'%#'+!SPR!5)!$%2)+#')!&'+*()5(<*+&)&'+#')!$(&&%#(!+&&+*+3!)#!01'1*(3!)#-/1&)!)#!:1+&'(!7*1$$(8!"/!'*)77+*3!%#-.+!$+*!)!$%2)+#')!-(#!4%/%'')%!7+#+')-%3!&+46*%!-(41#:1+!+&&+*+!1#B)#0+2)(#+3!(!-(41#:1+!1#%!#(g%!$%'(7+#%!-.+3!#+/!6%46)#(!-(#!-)'(&-.+/+'*(!$(5(-)'%*)(!7+#+')-%4+#'+!5+0)-)'%*)(3!?!)#!7*%5(!5)!5+'+*4)#%*+!/B)#)2)(!5+/!5%##(8!!

L1%#5(!)/!6%46)#(!&,)/1$$%!&'+*()5(<5)$+#5+#2%!(!&'+*()5(<*+&)&'+#2%!5($(!1#!-)-/(!5)!Q!4+&)3!'*%5)2)(#%/4+#'+!&)!?!&+4$*+!0%''%!/%!6)($&)%!*+#%/+8!M//%!6)($&)%3!%//+!,(/'+!&)!*)&-(#'*%,%!1#!:1%5*(!%!/+&)(#)!4)#)4+3!4%!&($*%''1''(!#+)!$%2)+#')!*+&)&'+#')!&)!*+$+*'%,%!)#,+-+!-(#!1#%!-+*'%!0*+:1+#2%!1#(!&'%'(!5)!7/(4+*1/(&-/+*(&)!0(-%/+!&+74+#'%*)%8!

E%!^b!4+46*%#(&%!+!/%!7/(4+*1/(&-/+*(&)!0(-%/+!

&+74+#'%*)%3!$*)4%!*)'+#1'+!$%'(/(7)+!#+''%4+#'+!5)&')#'+3!&+46*%#(!(77)!+&&+*+!51+!+#')'>!&'*+''%4+#'+!1#)'+3!+!)/!*)&-(#'*(!5+//B1#%!(!5+//B%/'*%!)#!1#!5%'(!$%2)+#'+!5)$+#5+*+66+!+&&+#2)%/4+#'+!5%/!4(4+#'(!)#!-1)!&)!,%!%!0%*+!/%!6)($&)%3!+!/%!7/(4+*1/(&-/+*(&)!0(-%/+!&+74+#'%/+!*%$$*+&+#'+*+66+!1#%!0%&+!5)!5%##(!$)F!%,%#2%'%8!L1)3!,(/+#5(3!&)!*)'(*#%!%/!5)&-(*&(!)#)2)%/+!&1//B)4$(*'%#2%!5+//%!:1('%!*+&)51%!5)!$(5(-)')8!!

b+)!$%2)+#')!&'+*()5(<*+&)&'+#')!&)!1')/)22%#(!)#!7+#+*+!-)-/(&$(*)#%3!*)'1g)4%6!(!-)-/(0(&0%4)5+3!-(#!'1'')!)!$*(6/+4)!5)!7*%,+!'(&&)-)'>!)44%7)#%6)/)8!H1*'*($$(3!$+*N3!&(/(!1#%!$)--(/%!$%*'+!5)!:1+&')!$%2)+#')!('')+#+!/%!*+4)&&)(#+!-(#!/B)441#(&($$*+&&(*+G!5B%/'*%!$%*'+3!-(4+!&)!5)-+,%3!:1+&')!&(#(!#+//%!4%77)(*!$%*'+!5+)!-%&)!:1%5*)!7+#+')-)!4)&-(#(&-)1')8!L1)#5)3!/%!7+&')(#+!5)!:1+&')!$%2)+#')!?!5)00)-)/+!+!$*)#-)$%/4+#'+!0)#%/)22%'%!%//%!/)4)'%2)(#+!5+//%!$*('+)#1*)%3!(6)+''),(!-.+!&)!$1N!*%77)1#7+*+!D!%!,(/'+!%#-.+!)#!4(5(!4(/'(!&(55)&0%-+#'+!D!-(#!7/)!M\a<"!+5!)!&%*'%#)8!

"#!%/-1#)!-%&)3!/%!4%/%'')%!%!/+&)(#)!4)#)4+!?!-(#7+#)'%!+!&)!$*+&+#'%!:1)#5)!7)>!%//%!#%&-)'%G!)#!:1+&')!-%&)!)!6%46)#)!$(&&(#(!*)&1/'%*+!$(&)'),)!%//(!&-*++#)#7!$+*!/B)$(')*()5)&4(!-(#7+#)'(!$()-.[3!%!-%1&%!5+//%!$*('+)#1*)%3!$+*5(#(!/%!Vq^8!!

_+-(*&(!

Al ME, la membrana basale ha un decorso tortuoso e si

apprezza la "fusione" completa dei pedicelli.

Per definizione nella glomerulonefrite a lesioni minime i

glomeruli appaiono sostanzialmente normali

Page 36: sbobinature nefro_0 - SkyDrive

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

)

`%$/(,1%$0-%(,$0')+$-"%()0(&/(*#"%()

L1+&'(!?!1#!:1%5*(!$*(/)0+*%'),(!-.+!&)!,+*)0)-%!:1%#5(!&)!?!%,1'%!/%!4(*'+!5+/!QP<SPR!5+)!$(5(-)')8!O)!5+&-*),+,%#(!-/%&&)-%4+#'+!0(*4+!$*)4)'),+!+!0(*4+!&+-(#5%*)+8!E%!5+0)#)2)(#+!5)!0(*4+!@$*)4)'),+A!5+*),%!5%/!0%''(!-.+!#+//+!6)($&)+!&)!+*%#(!*)&-(#'*%')!)#!%/-1#)!-%&)!"7X!%!/),+//(!7/(4+*1/%*+G!)#!&+71)'(3!&)!-%$e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kO3!:1)#5)3!?!4(/'(!)4$+7#%'),%!$+*-.[!&)!*)&-.)%!5)!+&&+*+!+&-/1&)!5%//%!$(&&)6)/)'>!5)!+00+''1%*+!)/!'*%$)%#'(8!!

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

"#!&+71)'(3!-)!&)%4(!%--(*')!-.+!1#%!:1('%!5+)!$%2)+#')!-(#!%/'+*%2)(#)!7+#+')-.+!$+*5+!-(41#:1+!)/!'*%$)%#'(8!L1+&'(3!$+*-.[!)#!%/-1#)!5)!:1+&')!-%&)!/%!$*('+)#%!-(#,(/'%!?!'('%/4+#'+!4%#-%#'+3!#(#!&)#'+')22%'%!Y5+/+2)(#)!'('%/)3!41'%2)(#)!&'($Z!+!:1)#5)!)/!&)&'+4%!)441#)'%*)(!5+/!6%46)#(!#(#!*)-(#(&-+!-(4+!&+/0!:1+//%!&'+&&%!$*('+)#%!$*+&+#'+!#+)!$(5(-)')!5+/!*+#+!'*%$)%#'%'(8!

a&)&'+!$()!)/!a1"3,$)0(-$*3",'$3!:1+//(!$)F!0*+:1+#'+3!-.+!)/!-/%&&)-(!-%&(!5)!0a1'%'C,'$)#,")/"00")+'%#,"*#()()/"00")3")+'%#,",(Q)

M!$%*'+!/+!)#0+2)(#)!5%!l"h!+!lqh3!)#0%'')3!$+*!'1''+!/+!%/'*+!,(-)!5)!:1+&'(!+/+#-(3!/%!-)0*%!?!$*($*)(!:1+&'(!&:1)/)6*)(!'*%!4%&&%!0)/'*%#'+!+!4%&&%!5%!0)/'*%*+8!L1+&'(!7+#+*%!1#%!&)'1%2)(#+!5)!)$+*0)/'*%2)(#+!

Condizioni morbose che possono provocare una

GSF secondaria •  Infezioni virali (HIV, epatite B) ! •  Farmaci (eroina, analgesici) •  Neoplasie (linfomi, altre neoplasie) •  Malattie congenite renali (oligonefronia,

ipoplasia segmentaria) •  Ridotta massa nefronica (agenesia renale

unilaterale)! •  Uropatia ostruttiva •  Reflusso vescico-ureterale •  Obesità grave •  Trapianto renale

Page 37: sbobinature nefro_0 - SkyDrive

-.+!-%1&%!5%##(!7/(4+*1/%*+!+!:1)#5)!$*('+)#1*)%8!

H+*!:1%#'(!*)71%*5%!/Bl"h3!+&)&'+!1#!:1%5*(!$%*')-(/%*+!-.+!&)!&,)/1$$%!#+)!$%2)+#')!l"hw3!-.)%4%'(!-(//%$&)#7!7/(4+*1/($%'.o8!O)!,+5+!&($*%''1''(!#+7/)!%0*(%4+*)-%#)!#+7/)!O'%')!T#)')8!!

V+*%$)%!

H+*!/%!'+*%$)%3!?!#+-+&&%*)(!$*)4%!5+'+*4)#%*+!/%!-%1&%!5+//%!^OkO8!b+//+!0(*4+!5%!&:1)/)6*)(!'*%!4%&&%!#+0*(#)-%!+!4%&&%!5%!0)/'*%*+!/%!'+*%$)%!4)7/)(*+!?!:1+//%!-(#!M\a<"!(!&%*'%#)-)8!b+//+!0(*4+!-.+!&)!&(&$+''%#(!&1!6%&+!)441#(/(7)-%3!&)!)4$)+7%#(!&'+*()5)!+5!)441#(&($$*+&&(*)8!!

!

!

A9 ^$,/()!,$%'+(,"#'7())

< ^/(4+*1/($%')%!%!5+$(&)')!4+&%#7)%/)!5)!"7M!< ^/(4+*1/(#+0*)'+!$*(/)0+*%'),%!+#5(-%$)//%*+!(!$(&'<)#0+''),%!< ^/(4+*1/(#+0*)')!4+46*%#(<$*(/)0+*%'),+!< ^/(4+*1/(#+0*)'+!$*(/)0+*%'),%!+g'*%-%$)//%*+!

!!!

`%$/(,1%$*(+,'#()")3(6$0'#')/(0"*&'"%')3')R&S)

aB!/%!0(*4%!5)!7/(4+*1/(#+0*)'+!$*)4)'),%!$)F!-(41#+!5+/!4(#5(8!O)!$1N!$*+&+#'%*+!-(#!5),+*&)!:1%5*)3!4%!$)F!0*+:1+#'+4+#'+!-(#!%#(4%/)+!1*)#%*)+!)&(/%'+3!4+#'*+!)/!$%2)+#'+!

7(5+!5)!61(#%!&%/1'+8!!

M#-.+!/B+4%'1*)%!*)-(**+#'+!D!&$+&&(!%&&(-)%'%!%!+$)&(5)!)#0+''),)!D!$1N!+&&+*+!1#%!0(*4%!5)!$*+&+#'%2)(#+!-/)#)-%!%66%&'%#2%!')$)-%G!/B+4%'1*)%!5%!#+0*($%')%!%5!"7M!?!')$)-%4+#'+!0'*+",'*&'#'-"3!-)(?!&)#-*(#%!%5!1#!+$)&(5)(!5)!0%*)#7)'+!+!0+66*+!Y4+#'*+!:1+//%!$(&'<&'*+$'(-(--)-%!?!6$0#L+",'*&'#'-"Z8!!

!

Sindromi cliniche associate alle principali forme di glomerulonefrite

Sindrome nefrosica

Sindrome nefritica

Anomalie urinarie

Ematuria isolata

Malattia a lesioni minime +++++ - ++ -/+

GN membranosa ++++ + ++ -/+

GS focale e segmentale +++ + ++ -/+

Nefropatia ad IgA ++ +++ ++++ ++++

GN membranoproliferativa +++ +++ ++++ -/+

GN proliferativa endocapillare + ++++ ++++ ++

GN a semilune + ++++ ++++ -

Sindromi cliniche associate alle principali forme di glomerulonefrite

Sindrome nefrosica

Sindrome nefritica

Anomalie urinarie

Ematuria isolata

Malattia a lesioni minime +++++ - ++ -/+

GN membranosa ++++ + ++ -/+

GS focale e segmentale +++ + ++ -/+

Nefropatia ad IgA ++ +++ ++++ ++++

GN membranoproliferativa +++ +++ ++++ -/+

GN proliferativa endocapillare + ++++ ++++ ++

GN a semilune + ++++ ++++ -

Page 38: sbobinature nefro_0 - SkyDrive

!

"/!5+$(&)'(!4+&%#7)%/+!?!$(&&)6)/+!7*%2)+!%//%!$*+&+#2%!5)!*+-+''(*)!$+*!k-"!)#!&+5+!4+&%#7)%/+8!b+/!SPR!5+)!-%&)!&)!*)&-(#'*%!1#!%14+#'(!5+//+!"7M!&)+*)-.+!+5!)441#(-(4$/+&&(!-)*-(/%#')!-(#'+#+#')!"7M8!

V1''%,)%3!&)!-(#(&-(#(!%#-.+!+$,/()0(-$*3",'(G!+&&+!&)!$*+&+#'%#(!')$)-%4+#'+!)#!$%2)+#')!-(#!5)0+'')!5+//B)441#)'>!41-(&%/+G!

< O"%"##'")-(%'"-")< O$,C$)3');,$.*)< U(##$-$%'#()1%-(,$0")< !$,6$,")3')<-.$(*%('*Lh(*$-.3!-(&')'1)'(!5%!#+0*($%')%!%5!"7M3!%*'*%/7)+!+!

$(*$(*%!,%&-(/%*+G!&)!,+5+!4(/'(!&$+&&(!#+)!6%46)#)!+!#+7/)!%5(/+&-+#')8!V%/,(/'%!$(&&(#(!+&&+*+!$*+&+#')!%#-.+!5)&'1*6)!7%&'*()#'+&')#%/)8!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

La Nefropatia ad IgA, descritta per la prima volta nel 1968, è la forma di glomerulonefrite primitiva più comune del mondo. E’ una forma a patogenesi anticorpo-mediata, nella quale i depositi immunologici si depo-sitano nel mesangio. I depositi si formano in circolo, e rimangono intrappolati a livello glomerulare a c a u s a d i u n a a l t e r a t a glicosilazione che ne altera la clearance e che ne favorisce l’uptake da parte delle cellule mesangiali, facendo produrre citochine che favoriscono la proliferazione mesangiale.

Nefropatia ad IgA

La glomerulonefrite da depositi di IgA è una glomerulonefrite con impegno prevalentemente mesangiale, che si manifesta soprattutto con ematuria. Questa può essere sia macro che microscopica e si può talora associare a proteinuria, raramente nel range nefrosico. Era una malattia un tempo scarsamente conosciuta anche per il fatto che l’ematuria isolata era sovente attribuita a cause urologiche ed i pazienti non erano sottoposti a biopsia renale. Da quando la pratica della biopsia renale si è andata estendendo anche all’ematuria isolata, la glomerulonefrite a depositi di IgA è diventata la GN più diffusa nel mondo. Rappresenta il 30-50% delle glomerulonefriti in Asia, il 20-25% in Europa ed il 5-10% negli Stati Uniti; tale differente prevalenza è in parte legata alle differenze nell’uso della biopsia renale cui abbiamo sopra accennato.

Page 39: sbobinature nefro_0 - SkyDrive

H*+&+#'%2)(#+!\/)#)-%!

!

!

_+-(*&(!

!

V+*%$)%!

b+)!-%&)!-(#!$*('+)#1*)%!&)!)4$)+7%#(!M\a<"!+!&%*'%#)3!&+!/%!$*('+)#1*)%!?!/)+,+8!O+!/%!$*('+)#1*)%!?!4%77)(*+!5)!W7U5)+3!&)!1&%#(!7/)!&'+*()5)8!O+!&)!,%!(/'*+!)!K!73!&)!1')/)22%#(!7/)!)441#(&($$*+&&(*)8!

!

!

!

!

!

Modalità di presentazione clinica I pazienti affetti da nefropatia ad IgA si presentano di solito con una di queste sindromi cliniche: !

• Il 40-50% dei pazienti presenta uno o più episodi di ematuria macroscopica, di solito in concomitanza con eventi febbrili o infezioni respiratorie.

• Il 30-40% dei pazienti presenta ematuria microscopica persistente asintomatica e proteinuria di grado variabile.

• Meno del 10% dei pazienti si presenta con un quadro clinico a tipo sindrome nefritica acuta.

• porpora di Schonlein-Henoch: è la forma sistemica della malattia. Determina nefropatia ad IgA e si verifica più frequentemente nei bambini che negli adulti. I pazienti affetti da Schonlein-Henoch manifestano porpora, artralgie e coinvolgimento intestinale (vedi oltre).

• Una modalità di presentazione più rara è quella di una sindrome nefrosica. In questo caso, l’aspetto in microscopia ottica è quello di una malattia a les ion i min ime ma con intenso depos ito mesang ia le d i IgA all’immunofluorescenza.

Decorso clinico

•  La funzione renale peggiora progressivamente in circa il 40% dei pazienti, e circa la metà di questi volgono verso l’insufficienza renale terminale in circa 20 anni. Fattori predittivi di una prognosi sfavorevole sono la presenza di insufficienza renale al momento della diagnosi, una microematuria persistente, una proteinuria>1 g/die, lo sviluppo di pertensione o lesioni severe alla biopsia renale. Il 5% dei pazienti può sviluppare un’ipertensione maligna.

•  Depositi secondari di IgA si possono osservare nelle malattie epatiche croniche, nella dermatite erpetiforme, nella psoriasi, nella spondilite anchilosante, nel morbo celiaco, nelle malattie infiammatorie croniche dell’intestino, nei carcinomi, nella gammapatia monoclonale ad IgA, nell’nfezione da HIV e nella micosi fungoide.

Terapia

•  Inibitori dell’Enzima di Conversione dell’Angiotensina/e o sartanici Si sono dimostrati più efficaci degli altri anti-ipertensivi nel

ritardare la progressione verso l’insufficienza renale e nel ridurre la proteinuria, e vanno somministrati a tutti i pazienti, a prescindere dalla presenza di ipertensione e dal grado di proteinuria.

Se proteinuria> 1g/die: Cicli di Steroidi Riducono la perdita proteica nei soggetti che si presentano con grave

proteinuria, alcuni dati suggeriscono un effettivo vantaggio nel preservare la funzione renale a lungo termine.

Se proteinuria> 3g/die: Cicli di Steroidi da soli o in associazione ad immunosoppressori G l i i mm u n o s o p p r e s s o r i s o n o i n d i c a t i s o p r a t t u t t o s e v i è

deterioramento della funzione renale.

Studi recenti relativi al ruolo degli ACE inibitori e degli steroidi nella nefropatia ad IgA hanno modificato la trerapia della Nefropatia ad IgA:

Page 40: sbobinature nefro_0 - SkyDrive

`%$/(,1%$*(+,'#()6,$%'+(,"#'7")(*3$-"6'%%",()

L1+&'%!0(*4%!?!$+*!-+*')!%&$+'')!&)4)/!%//%!#+0*($%')%!%5!"7M3!4%!)/!5+-(*&(!+!/B+$)5+4)(/(7)%!&(#(!-(4$/+'%4+#'+!5),+*&)8!L1+&'%!?!/%!0(*4%!$*+-+5+#'+4+#'+!#('%!-(#!)/!#(4+!5)!&%$/(,1%$*(+,'#()6$0#L0#,(6#$-$--'-")Y$(&'<0%*)#7)')-%Z8!

EB%&$+''(!)&'(/(7)-(!?!-%*%''+*)22%'(!5%!1#B)#'+#&%!

$*(/)0+*%2)(#+!4+&%#7)%/+!+5!+#5('+/)%/+!%//B)#'+*#(!5+/!7/(4+*1/(3!-(#!)#0)/'*%2)(#+!5)!7*%#1/(-)')!+!-+//1/+!4(#(#1-/+%'+3!*+&$(#&%6)/)!5+/!5%##(8!

M#-.+!/%!7/(4+*1/(#+0*)'+!$*(/)0+*%'),+!+#5(-%$)//%*+!&)!$*+&+#'%!7+#+*%/4+#'+!-(#!1#B+4%'1*)%!)&(/%'%G!%!5)00+*+#2%!5+//B+4%'1*)%!5+//%!#+0*($%')%!%5!"7M3!-.+!?!')$)-%4+#'+!&)#0%*)#7)')-%3!:1+//%!5%!^Ha\!&)!$*+&+#'%!7+#+*%/4+#'+!ALD)0(##'/"*(!5($(!/B+$)&(5)(!0%*)#7)')-(!+5!?!:1)#5)!$(&'<0%*)#7)')-%8!L1+&'(3!$+*-.[!/%!^Ha\!?!

1#%!$%'(/(7)%!7/(4+*1/%*+!5%!5+$(&)'(!5)!'//1*$-$/6%(00'3!+!$+*-.[!:1+&'+!4%-*(4(/+-(/+!&)!0(*4)#(!?!#+-+&&%*)(!-.+!&)!&,)/1$$)!-(4$/+'%4+#'+!/%!*)&$(&'%!)441#)'%*)%!5+//B(&$)'+8!

L1+&'%3!$+*N3!?!/%!0(*4%!-(#-/%4%'%3!(*4%)!%66%&'%#2%!*%*%!#+//B%46)'(!5+//%!4+5)-)#%!7+#+*%/+!D!&+66+#+!%#-(*%!*+/%'),%4+#'+!0*+:1+#'+!)#!%46)'(!$+5)%'*)-(8!\)N!-.+!&)!,+5+!0*+:1+#'+4+#'+3!)#,+-+3!&(#(!/+!/'-,$(/"#1,'()6$0#L'*+(##'7(9!H+*'%#'(3!/%!4(5%/)'>!5)!$*+&+#'%2)(#+!5+//%!^Ha\!$1N!+&&+*+G!

< <'*3,$/()*(+,'#'-")"-1#"3!$*+&+#'%2)(#+!%-1'%!-(#!6%46)#(!(/)71*)-(3!-(#!+5+4%!5+/!,(/'(3!

4%-*(+4%'1*)%3!1#%!-+*'%!:1('%!5)!$*('+)#1*)%!+5!)$+*'+#&)(#+8!)< S*$/"%'()1,'*",'()I/$3(0#")/'-,$(/"#1,'"3!'%/,(/'%!%#-.+!/)+,+!$*('+)#1*)%Z)

9/'*+!%//B)#0)/'*%2)(#+!/+1-(-)'%*)%3!%#-.+!/B%''),%2)(#+!4%&&),%!5+/!-(4$/+4+#'(!%5!($+*%!5+7/)!)441#(-(4$/+&&)!?!1#!%&$+''(!)4$(*'%#')&&)4(!#+/!5%##(!7/(4+*1/%*+8!O+!%#5)%4(!%!0%*+!1#B)441#(0/1(*+&-+#2%!$+*!)/!\K3!,+5)%4(!-.+!/+!4+46*%#+!6%&%/)!&(#(!

A forte ingrandimento è evidente l'intensa ipercellularità glomerulare, in cui sono riconoscibili numerose cellule infiammatorie endoluminali come i leucociti polimorfonucleati e cellule monocitarie.

GLOMERULONEFRITE PROLIFERATIVA ENDOCAPILLARE

L'utilizzo di anticorpi monoclonali, con metodo immunoistochimico,

ha permesso di quantizzare meglio l'entità e le caratteristiche delle

cellule infiammatorie coinvolte nel danno glomerulare. L'anticorpo

contro l'antigene comune leucocitario conferma la massiva infiltrazione di queste cellule nel

flocculo glomerulare.

Page 41: sbobinature nefro_0 - SkyDrive

&')$%'+!5)!0*%2)(#+!-(4$/+4+#'%*+3!%!'+&')4(#)%*+!/%!4%&&),%!%''),%2)(#+!5+/!&)&'+4%!5+/!-(4$/+4+#'(8!"#0%'')3!)#!:1+&'%!$%'(/(7)%!?!')$)-(!)/!*)&-(#'*(!5)!1#%!'6$-$/6%(/(*#(/'"!5%!-(#&14(3!-.+!?!)#,+-+!%&&(/1'%4+#'+!%&&+#'+!#+//%!#+0*($%')%!%5!"7M!Y+!:1)#5)!?!1#!61(#!-*)'+*)(!5)!5)&')#2)(#+Z8!"/!*)+#'*(!5+//%!-(4$/+4+#'+4)%!#+/!*%#7+!#(*4%/+!'+&')4(#)%!/%!*+4)&&)(#+!5+//%!4%/%'')%8!!

!

a2)(/(7)%!+!$%'(7+#+&)!

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k-8!!

_+-(*&(!

aB!+&'*+4%4+#'+!)4$(*'%#'+!*)-(#(&-+*+!$*(#'%4+#'+!1#%!7/(4+*1/(#+0*)'+!$(&'<)#0+''),%C!)#0%'')3!&+!#+)!6%46)#)!/%!$*(7#(&)!?!('')4%!D!-(#!*+4)&&)(#+!-(4$/+'%!(''+#1'%!)#!7+#+*+!+#'*(!;!4+&)3!#+7/)!%51/')!%")6,$&*$0')i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a1(*2")3(&%')(6'0$3')-$*-%"/"#'!-(#!4%-*(+4%'1*)%8!!

E%!5)%7#(&)!?!$)F!&+4$/)-+!5($(!1#!+$)&(5)(!5)!&-%*/%'')#%3!$+*-.[!)#!:1+&'(!-%&(!&(#(!$*+,)&')!+&%4)!5+//+!1*)#+!%!51+!&+'')4%#+!5%//B+$)&(5)(3!+!:1)#5)!?!0%-)/+!)/!*)&-(#'*(!5)!1#%!4(5+&'%!4)-*(+4%'1*)%8!

!

V+*%$)%!

aB!1#%!'+*%$)%!5)!&1$$(*'(3!$+*-.[!&(/)'%4+#'+!/%!4%/%'')%!,%!)#!*+4)&&)(#+!&$(#'%#+%8!"$+*'+#&)(#+!+!&(,*%--%*)-(!,(/+4)-(!$(&&(#(!+&&+*+!'*%''%')!-(#!5)1*+')-)!+5!%/'*)!

Page 42: sbobinature nefro_0 - SkyDrive

0%*4%-)!%#')<)$+*'+#&),)3!&+4$*+!5%!1&%*+!-(#!%''+#2)(#+8!M/-1#)!$%2)+#')3!#(#(&'%#'+!/%!'+*%$)%!+!/%!*)&(/12)(#+!5+/!:1%5*(3!-(#')#1%#(!%5!+&&+*+!)$+*'+&)8!

!

`%$/(,1%$*(+,'#()/(/C,"*$6,$%'+(,"#'7")

M#-.+!:1+&'%!?!1#%!0(*4%!$*(/)0+*%'),%3!:1)#5)!%&&(-)%'%!%5!(/"#1,'"G)06(00$)/'-,$0-$6'-"9)O)!'*%''%!$+*N!5)!1#%!0(*4%!%!$(#'+3!-(#!%&$+'')!$*(/)0+*%'),)!-.+!-(+&)&'(#(!-(#!1#!)&$+&&)4+#'(!5+//%!4+46*%#%!6%&%/+G!:1+&'(!&$)+7%!$+*-.[!4(/')!5)!:1+&')!&(77+'')!&)!$*+&+#')#(!%#-.+!-(#!1#%!0'*3,$/()*(+,$0'-")3')1*")-(,#")'/6$,#"*2"9))

)

977)!&)!4+''+!0(*'+4+#'+!)#!5166)(!/B+&)&'+#2%!5+/!')$(!"""8!!

E%!7/(4+*1/(#+0*)'+!4+46*%#($*(/)0+*%'),%!?!4(/'(!)4$(*'%#'+!$()-.[!#+/!;PR!5+)!-%&)!&)!%&&(-)%!"%%5'*+(2'$*()3")h;jQ!#+)!$%2)+#')!-(#!+$%')'+!\!#('%!?!&+4$*+!6+#+!*)-+*-%*+!/%!7/(4+*1/(#+0*)'+!4+46*%#($*(/)0+*%'),%3!+!#+)!$%2)+#')!-(#!7/(4+*1/(#+0*)'+!4+46*%#($*(/)0+*%'),%!6)&(7#%!&+4$*+!*)-+*-%*+!/B)#0+2)(#+!5%!l\h8!

H%'(7+#+&)!

E%!0(*4%!5)!')$(!"!?!/%!$)F!0*+:1+#'+!)#!-/)#)-%!+!$1N!%&&(-)%*&)!%!5),+*&+!-(#5)2)(#)!-/)#)-.+G!

< ;,'$&%$C1%'*(/'")'*)-$,0$)3')(6"#'#();)< ;,'$&%$C1%'*(/'")0(*2")(6"#'#();)I_'*+$/'G)%(1-(/'")%'*+"#'-.(G)/"%"##'()

"1#$'//1*'J)O+!&)!*)&-(#'*%!1#%!7/(4+*1/(#+0*)'+!4+46*%#($*(/)0+*%'),%3!?!)4$(*'%#'+!*)-.)+5+*+!)/!5(&%77)(!5+//+!-*)(7/(61/)#+!-.+3!&+!$(&)'),(3!5+,+!)#51*-)!%!*)-+*-%*+!/%!4%/%'')%!5)!6%&+3!&)%!+&&%!/B+$%')'+!\!(!1#B%/'*%!-(#5)2)(#+!-.+!$1N!-%1&%*+!-*)(7/(61/)#+4)%8!

< _1610)(,'#(/"#$0$)0'0#(/'-$)< O"%"##'()%'*+$6,$%'+(,"#'7()-,$*'-.()< R*+(2'$*()3")hKj)< S%#,()'*+(2'$*')C"##(,'-.()I(0Q)(*3$-",3'#'J)()7',"%')

Glomerulonefrite membranoproliferativa L’associazione della glomerulonefrite membranoproliferativa con numerose entità nosologiche hanno suggerito che non si tratti di un’unica entità etiopatogenetica. Tuttavia il recente riconoscimento della relazione causale tra l’infezione da virus C e la glomerulonefrite membranoproliferativa suggerisce che questo virus sia coinvolto in almeno il 60% delle forme prima ritenute idiopatiche. Sulla base delle differenze istopatologiche si riconoscono diverse varianti:

• Tipo I: caratterizzata da depositi mesangiali e subendoteliali.

• Tipo II: (malattia a depositi densi) caratterizzata da depositi lineari interrotti nella lamina densa della membrana basale.

• Tipo III: una variante più rara, caratterizzata da caratteristiche comuni a l l a t i p o I e a l l a t i p o I I o d a l l ’ a c c u m u l o d i n u o v o materiale organizzato in strati a livello della membrana basale.

Page 43: sbobinature nefro_0 - SkyDrive

E%!-%1&%3!#+)!-%&)!%&&(-)%')!%5!l\h3!&+46*%!:1)#5)!+&&+*+!)5+#')0)-%6)/+!#+//%!-,'$&%$C1%'*(/'"9)E+!-*)(7/(61/)#+3!%!,(/'+!5)*+''%4+#'+!-(4$/+&&%'+!%/!,)*1&!\3!&)!5+$(&)'%#(!%/!/),+//(!7/(4+*1/%*+8!

!

"#!7+#+*%/+3!#+//+!0(*4+!5)!')$(!"!&)!*)')+#+!+&&+*+!$*+&+#'+!1#!3(+'-'#)*(%%")-%(","*-()3(&%')'//1*$-$/6%(00'3!-.+!&)!'*%51-+!)#!1#B%''),%2)(#+!-*(#)-%!5+/!-(4$/+4+#'(3!)!-1)!/),+//)!&(#(!)#0%'')!0/1''1%#')!)#!:1+&'%!$%'(/(7)%8!!

H+*!:1%#'(!*)71%*5%!/%!+$,/")3')#'6$)RR3!4(/'(!$)F!*%*%3!+&)&'(#(!%#(4%/)+!7+#+')-.+!(!,+*)!+!$*($*)!%1'(%#')-(*$)!-.+3!6/(--%#5(!7/)!)#)6)'(*)!0)&)(/(7)-)!5+/!-(4$/+4+#'(3!5+'+*4)#%#(!1#B%''),%2)(#+!5+//%!-%&-%'%!-(4$/+4+#'%*+!%''*%,+*&(!/%!,)%!%/'+*#%'),%8!

_+-(*&(!

L1+&'(!')$(!5)!7/(4+*1/(#+0*)'+!.%!1#%!$*(7#(&)!)#0%1&'%3!)#!:1%#'(!+&'*+4%4+#'+!5)00)-)/+!5%!-1*%*+G!/%!'+*%$)%!?!)#0%'')!*),(/'%!%//%!+*%5)-%2)(#+!5+/!,)*1&!\3!(6)+''),(!#(#!&+4$*+!*%77)1#7)6)/+8!"#(/'*+3!/B)#'+*0+*(#!1')/)22%'(!$+*!/%!'+*%$)%!5+//B)#0+2)(#+!5%!l\h!.%!)/!$*(6/+4%!5+//B)#512)(#+!5+//%!$*('+)#1*)%3!$+*!-1)!)/!'*%''%4+#'(!&'+&&(!$1N!%77*%,%*+!)/!:1%5*(!*+#%/+8!

"#!%/'+*#%'),%!&)!$(&&(#(!1')/)22%*+!&'+*()5)!+5!)441#(&($$*+&&(*)3!-.+!&+46*%#(!#(#!%,+*+!+00+'')!5+/+'+*)!)#!'+*4)#)!5)!*)%''),%2)(#+!(!*+-*15+&-+#2%!5+//B)#0+2)(#+!5%!,)*1&!\8!

!

`%$/(,1%$*(+,'#()")0(/'%1*()I(c#,"-"6'%%",(J)

"#!:1+&'%!7/(4+*1/(#+0*)'+!$*(/)0+*%'),%3!/+!-+//1/+!$*(/)0+*%#')!&(#(!/+!-(%%1%()0#"/'*"%')3(%%")-"601%")3')K$T/"*9)_%!:1+&'(!0+#(4+#(!$*(/)0+*%'),(!#%&-+!1#%!/+&)(#+!5+/!'1''(!$%*')-(/%*+3!/%!0(/'%1*"9))

_%/!$1#'(!5)!,)&'%!-/)#)-(3!/B+&(*5)(!?!&$+&&(!-%*%''+*)22%'(!5%!"*$/"%'()*(%)0(3'/(*#$3!'%/,(/'%!-(#!1#!:1%5*(!&)4)/+!%//%!&)#5*(4+!#+0*)')-(8!\)N!-.+!5+'+*4)#%!)/!:1%5*(!-/)#)-(3!-(41#:1+3!#(#!?!'%#'(!/B%/'+*%2)(#+!5+/!&+5)4+#'(3!:1%#'(!$)1''(&'(!'%),"6'3$)3(-%'*$)3(%%")+1*2'$*(),(*"%(3!'%#'(!-.+!:1+&'%!0(*4%!,)+#+!%#-.+!5+0)#)'%!@7/(4+*1/(#+0*)'+!*%$)5%4+#'+!$*(7*+&&),%A8!

977)!&%$$)%4(!-.+!+&)&'(#(!#,()#'6')5)!7/(4+*1/(#+0*)'+!%!&+4)/1#+3!5)&')#')!7*%2)+!%7/)!&'15)!5)!)441#(0/1(*+&-+#2%G!

< 8'6$)R3!0(*4%!-%1&%'%!5%//%!$*+&+#2%!5)!"*#'-$,6')"*#'L/(/C,"*")C"0"%()5)*+'')!-(#'*(!)/!-(//%7+#+!"h8!"/!5%##(!$1N!-()#,(/7+*+!&(/(!)/!*+#+3!($$1*+!+&'+#5+*&)!%#-.+!%/!6$%/$*(G!)#!:1+&'(!1/')4(!-%&(!/%!4%/%'')%!$*+#5+!)/!#(4+!5)!<'*3,$/()3')`$$36"0#1,(G)+!/%!$*+&+#2%!5)!+4('')&)!-)!$1N!)#5)*)22%*+!#+//%!5)%7#(&)9)"/!')$)-(!:1%5*(!%//B)441#(0/1(*+&-+#2%!?!:1+//(!%!@+1/$)3')0'&",(##"A8)

Si ritiene che la glomerulonefrite membrano-proliferativa sia provocata dalla deposizione di immunocomplessi a livello glomerulare, in particolare sul versante interno sottoendoteliale della membrana basale, oltre che a livello mesangiale, con attivazione delle cellule mesangial i ed espansione del la matrice mesangiale, che stimola la interposizione del mesangio fino alla periferia del capillare glomerulare in sede sottoendoteliale, con conseguente "duplicazione" della stessa (doppio contorno della MBG).

Page 44: sbobinature nefro_0 - SkyDrive

)< 8'6$)RR3!0(*4%!5%!'//1*$-$/6%(00'9)"#!:1+&'(!-%&(!/%!7/(4+*1/(#+0*)'+!%!

&+4)/1#+!$1N!*%$$*+&+#'%*+!1#%!0%&+!%--+/+*%'%!+!*%$)5%4+#'+!$*(7*+&&),%!5)!%/'*+!0(*4+!5)!7/(4+*1/(#+0*)'+!$*(/)0+*%'),%8!)

)

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

_()+$,/()6"1-'//1*'!$(&&(#(!+&&+*+!%&&(-)%*&)!%!K!')$)!5)!,%&-1/)')3!51+!&)&'+4)-.+!+5!1#%!&$+-)0)-%8!L1+//+!&)&'+4)-.+!&(#(!/%!&,"*1%$/"#$0')3')k(&(*(,!+!/%!0'*3,$/()3');.1,&L<#,"1008!b+//%!t+7+#+*!/B)#'+*+&&%4+#'(!*+#%/+!?!0*+:1+#'+!4%!#(#!(66/)7%'(*)(C!)!$%2)+#')!5)!&(/)'(!.%##(!1#%!&'(*)%!5)!)#0+2)(#)!*)-(**+#')!5+//+!,)+!%+*++!&1$+*)(*)!-.+!#(#!$%&&%#(8!"/!*)&-.)(!$*)#-)$%/+!?!1#!7*%,+!-()#,(/7)4+#'(!$(/4(#%*+3!-(#!4%&&),+!+4(**%7)+!+!:1%5*)!5)!M`_O8!H+*!:1%#'(!*)71%*5%!/%!\.1*7<O'*%1&&3!+&&%!&)!%--(4$%7#%!%5!%&4%!7*%,+3!&)#1&)'+U*)#)'+!-*(#)-%!+5!+(&)#(0)/)%8!b+//%!t+7+#+*!&)!'*(,%#(!')$)-%4+#'+!-LS=;S)Y%#')<$*('+%&)!KZ3!4+#'*+!#+//%!\.1*7<O'*%1&&!&)!$(&&(#(!'*(,%*+!&)%!$<Mb\M!-.+!-<Mb\M3!4%!')$)-%4+#'+!&)!'*(,%#(!)!6LS=;S)Y%#')<XH9Z8!

E%!'+*2%!0(*4%!?!/%!/'-,$6$%'"*&'$'#(3!1#%!0(*4%!,%&-1/)')-%!-.+!)#'+*+&&%!6,(7"%(*#(/(*#())/!*+#+8!!

!

_%!#('%*+!-.+!/%!7/(4+*1/(#+0*)'+!$1N!%#-.+!+&&+*+!)/!:1%5*(!5B+&(*5)(!5)!1#%!5)!:1+&'+!,%&-1/)')C!)#(/'*+3!'1'')!)!$%2)+#')!-(#!,%&-1/)')!&(#(!'+#1')!&(''(!-(#'*(//(!$+*)(5)-%4+#'+!-(#!+&%4)!,%*)3!'*%!-1)!%#-.+!7/)!+&%4)!5+//+!1*)#+!Y$(-(!-(&'(&)3!&+4$/)-)Z3!-.+!$+*4+''(#(!5)!)#5),)51%*+!$*+-(-+4+#'+!1#!+,+#'1%/+!5%##(!*+#%/+8!

)

_+-(*&(!

_")6,$&*$0')3')a1(0#()+$,/()i)(0#,(/"/(*#()0(7(,"Q!)!$%2)+#')!&$+&&(!#(#!*)-+,(#(!)#!'+4$(!/%!5)%7#(&)!$()-.[!)!&+7#)!5)!5+'+*)(*%4+#'(!*%$)5(!5+//%!01#2)(#+!*+#%/+!Y#%1&+%3!,(4)'(3!4)%/7)+3!4%/+&&+*+Z!,+#7(#(!0%-)/4+#'+!)#'+*$*+'%')!-(4+!&)#'(4)!)#0/1+#2%/)8!"!$%2)+#')!$+*N!-(#')#1%#(!%!&'%*!4%/+G!%!:1+&'(!$1#'(!7/)!+&%4)!5+/!&%#71+!+,)5+#2)%#(!7)>!%2('+4)%!+!-*+%')#)#+4)%!+/+,%'%!+!5)!-(#&+71+#2%!?!+&'*+4%4+#'+!5)00)-)/+!)#'+*,+#)*+!-(#!+00)-%-)%8!L1+&')!$%2)+#')3!:1)#5)3!,%##(!)#-(#'*(!%//%!5)%/)&)3!&+!

La vasculite dei piccoli vasi è tipicamente caratterizzata da una necrosi massiva della parete vascolare con infiltrati infiammatori intra e perivascolari. Le lesioni di necrosi del flocculo e di proliferazione extracapillare sono assai variabili come intensità e diffusione da caso a caso o spesso all'interno di un singolo caso. Alla necrosi massiva si associa abitualmente una proliferazione extracapillare diffusa e circonferenziale, con quadro clinico di insufficienza renale a rapida progressione.

Page 45: sbobinature nefro_0 - SkyDrive

#(#!%55)*)''1*%!%//B+g)'1&8!O+!&)!)#'+*,)+#+!$*+-(-+4+#'+3!$+*N3!$(&&)%4(!&%/,%*+!/%!:1('%!5)!7/(4+*1/)!%#-(*%!#(#!-()#,(/'%8!d!&'%'(!5)4(&'*%'(!-.+!/%!-'-%$+$0+"/'3().%!1#%!-+*'%!+00)-%-)%!#+/!0%*!*)+#'*%*+!/+!&+4)/1#+3!:1%#5(!%#-(*%!#(#!&(#(!&-/+*(')-.+G!$*(6%6)/4+#'+3!:1+&'(!?!5(,1'(!%/!&1(!+00+''(!-)'(&'%')-(8!d!4(/'(!,+*(&)4)/+!-.+!/%!/+&)(#+!5+//%!&+4)/1#%!&)%!1#%!&(*'%!5)!-.(%$'3(3!-)(?!1#!'+#'%'),(!%6#(*4+!5)!*)$%*%*+!1#!+&'+&(!5%##(!-.+!&)!,+*)0)-%!)#!'+4$)!+&'*+4%4+#'+!*%$)5)8!!

!

H*)4%!5)!)#)2)%*+!-(#!)!6(/)!5)!-)-/(0(&0%4)5+!&+*,+3!$+*!4('),)!$*+-%12)(#%/)!+!/+7%/)3!/%!3$-1/(*#"2'$*()C'$6#'-")3')1*)a1"3,$)-.()&'10#'+'-.')%5'/6'(&$)3')a1(0#$)+",/"-$8!H+*'%#'(3!/+!0(*4+!%!&+4)/1#+!D!%#-.+!&+!4(/'(!%77*+&&),+!D!&(#(!5%!6)($&)%*+8!

!

!

^/(4+*1/(#+0*)'+!E1$)-%!

"/!EaO!?!1#%!4%/%'')%!$)1''(&'(!0*+:1+#'+!+!)/!*+#+!?!1#(!5+7/)!(*7%#)!$)F!0*+:1+#'+4+#'+!-()#,(/')G!)/!;P<=PR!5+)!$%2)+#')!-(#!EaO!&,)/1$$%#(!)#'+*+&&%4+#'(!*+#%/+!+!/%!7/(4+*1/(#+0*)'+!$1N!+&&+*+!)/!:1%5*(!5B+&(*5)(8!L1)#5)3!5%/!$1#'(!5)!,)&'%!-/)#)-(!%66)%4(!51+!$*(6/+4)G!

< V'"&*$0#'-",()'%)_4<)'*)1*)6"2'(*#()-.()07'%166")&%$/(,1%$*(+,'#()-$/()6,'/")/"*'+(0#"2'$*(9)

"#!:1+&'(!-%&(!#(#!?!5)00)-)/+3!)#!:1%#'(!+&)&'(#(!-*)'+*)!6+#!5+0)#)')8!T#(!&'*14+#'(!0(#5%4+#'%/+!?!/%!*)-+*-%!5+7/)!MbM!%!')'(/(!*)/+,%#'+!Y)#!$%*')-(/%*+!5+7/)!%#')<5&_bM!#%'),(Z3!4%*]+*&!4(/+-(/%*)!5+//%!4%/%'')%8!

< V'"&*$0#'-",()6,(-$-(/(*#()%5'*#(,(00"/(*#$),(*"%()*(%)6"2'(*#()-$*)_4<)*$#$9)

"#!:1+&')!$%2)+#')!&)!+00+''1%!$+*)(5)-%4+#'+!/B+&%4+!5+//+!1*)#+3!+!)#!-%&(!5)!-()#,(/7)4+#'(!*+#%/+!-%*%''+*)&')-%4+#'+!#+/!&+5)4+#'(!&)!'*(,%!5)!'1''(G!$*('+)#+3!+*)'*(-)')3!/+1-(-)')3!-)/)#5*)8!a&)&'(#(!$()!:1%5*)!&014%')!(!%#-.+!#+0*(&)!4(/'(!)4$(*'%#')8!b+)!$%2)+#')!-(#!EaO!/%!5)%7#(&)!5+//B)#'+*+&&%4+#'(!*+#%/+!?!'%/4+#'+!)4$(*'%#'+!-.+!/B)#5)-%2)(#+!%//%!6)($&)%!&)!$(#+!%#-.+!)#!$*+&+#2%!5)!$)--(/+!%/'+*%2)(#)!

Prognosi La glomerulonefrite da anticorpi anti-membrana non trattata ha una prognosi pessima sia quoad vitam che per quanto riguarda la funzione renale. Nei pazienti trattati, la funzione renale migliora in quelli con creatininemia < 600 µmol/L all’esordio, mentre la maggior parte di quelli con creatininemia più elevata necessiterà della dialisi. La prognosi è peggiore nei pazienti con emorragia polmonare, che rappresenta la principale causa di morte.

Circa il 75% dei pazienti con forme pauci-immuni ANCA-associate va in remissione, ed il 43% di questi è ancora in remissione dopo 4 anni. Il miglior fattore predittivo della perdita di funzione renale è anche in questo caso il valore della creatinina all’esordio. Tuttavia, alcuni pazienti che necessitano di dialisi all’esordio rispondono bene alla terapia; pertanto la dialisi non rappresenta in questo caso una controindicazione al trattamento.

Terapia

CORTICOSTEROIDI+CICLOFOSFAMIDE

Il solo esame importante per la prognosi è il livello di creatinina al momento della diagnosi. Pertanto la diagnosi precoce è il maggior determinante della

sopravvivenza sia dei reni che della vita del paziente. Un’insufficienza renale che richieda la

dialisi non è una controindicazione al trattamento.

Page 46: sbobinature nefro_0 - SkyDrive

5+/!&+5)4+#'(!D!%!5)00+*+#2%!5)!:1%#'(!%--%5+!#+//%!$+*&(#%!#(*4%/+3!)#!-1)!/%!6)($&)%!&)!0%!&(/(!&+!+&)&'+!1#B%/'+*%2)(#+!5)!1#!-+*'(!$+&(8!!

a&%4)!5%!*)-.)+5+*+!

!

!

\/%&&)0)-%2)(#+!

"/!EaO!?!1#%!4%/%'')%!/$%#$)-$/6%(00")3"%)61*#$)3')7'0#"),(*"%(3!)#!-1)!&)!*)-(#(&-(#(!&(&'%#2)%/4+#'+!&+)!:1%5*)!-(4$/+'%4+#'+!5),+*&)G!/+!$*)4+!:1%''*(!-/%&&)!5+&-*),(#(!:1%5*)!5)!7/(4+*1/(#+0*)'+!$*(/)0+*%'),%!-(#!7*%,)'>!5),+*&%8!!

E%!-/%&&+!:1)#'%!5+&-*),+!1#%!7/(4+*1/(#+0*)'+!4+46*%#(&%8!

E%!-/%&&+!&+&'%!5+&-*),+!1#%!7/(4+*1/(&-/+*(&)!0(-%/+!&+74+#'%/+3!(!7/(6%/+8!!

!

!

!

!

!

!

!

!

!

!

Esami di laboratorio

•  Esami di funzionalità renale (creatinina, azotemia, creatinina clearance)!

•  Esame delle urine standard e analisi del sedimento, proteinuria 24h

•  Indici di attività di malattia: ANA (anti-dsDNA), complemento (C3, C4, CH50), VES, proteina C reattiva (PCR). Livelli elevati di anti-dsDNA, di VES e bassi livelli di C3 e C4 sono associati con glomerulonefrite in fase di attività, specie nelle forme proliferative.

•  La nefrite lupica si associa in genere con una riduzione del filtrato del 30%, una proteinuria maggiore di 1g e una biopsia renale con segni di nefrite attiva.

Page 47: sbobinature nefro_0 - SkyDrive

!

!

!

!

World Health Organization Classification of Lupus Nephritis Classe I: la biopsia renale rivela un rene essenzialmente normale.

Non c’è evidenza clinica di malattia. Classe II: Glomerulonefrite mesangiale Classe IIA: Glomerulonefrite proliferativa mesangiale lieve MO: L’ipercellularità mesangiale è lieve o assente. IF: I depositi immunologici sono confinati al mesangio. ME: I depositi immunologici sono confinati al mesangio Classe IIB: Glomerulonefrite proliferativa mesangiale moderata MO: Ipercellularità mesangiale

confinata alle aree centrolobulari ed assenza di infiltrati, necrosi o sclerosi. IF: I depositi immunologici sono confinati al mesangio ME: I depositi immunologici sono confinati al mesangio

Manifestazioni cliniche: Alterazioni urinarie, ematuria, proteinuria.

Classe III: Glomerulonefrite proliferativa focale e segmentale MO: Aree di proliferazione glomerulare a carico delle cellule mesangiali ed

endoteliali, con infiltrato infiammatorio, necrosi e sclerosi. E’ coinvolta una porzione del glomerulo inferiore al 50%

IF: Depositi immuni diffusi a livello mesangiale e capillare. ME: Depositi immuni subendoteliali e mesangiali. Manifestazioni cliniche: Molti pazienti hanno un LES sistemico in fase attiva ed

un interessamento renale da lieve a moderato con ematuria e proteinuria. Una minoranza mostra un peggioramento della funzione renale e può progredire nella quarta classe.

World Health Organization Classification of Lupus Nephritis

Page 48: sbobinature nefro_0 - SkyDrive

!

!

!

!

!

!

!

!

Classe IV: Glomerulonefrite proliferativa diffusa MO: Proliferazione glomerulare soprattutto a carico delle cellule endoteliali

determinano una occlusione dello spazio capillare, infiltrato leucocitario, necrosi, semilune, sclerosi. Depositi ialini sono presenti nelle pareti capillari o nei vasi. Sono coinvolti diffusamente oltre il 50% dei glomeruli.

IF: Deposti immuni irregolari nel mesangio e nelle pareti dei capillari.

ME: Grandi depositi immuni sottoendoteliali o mesangiali sono presenti; occasionalmente anche depositi sottoepiteliali e intramembranosi

Manifestazioni cliniche: Ipertensione, edema, alterazioni del sedimento urinario, peggioramento della funzione renale, proteinuria nefrosica.

World Health Organization Classification of Lupus Nephritis

Classe V: Glomerulonefrite membranosa diffusa MO: Ispessimento diffuso della membrana basale glomerulare senza infiltrato

infiammatorio. All’impregnazione argentica sono osservabili depositi sottoepiteliali e “spikes”. Le lesioni membranose sono a volte associate a lesioni proliferative focali o diffuse.

IF: Depositi immuni nelle pareti capillari e a livello mesangiale.

ME: Depositi immuni sottoepiteliali e membranosi; i depositi endoteliali si osservano solo se c’è anche una componente proliferativa.

Manifestazioni cliniche: Segni clinici e di laboratorio di sindrome nefrosica, in genere associati a manifestazioni di attività el LES.

World Health Organization Classification of Lupus Nephritis

Page 49: sbobinature nefro_0 - SkyDrive

!

!

!

!

!

!

!

!

!

!

!

M!&+-(#5%!5+/!:1%5*(!-.+!*)&-(#'*)%4(!%//%!6)($&)%!-%46)%!(,,)%4+#'+!/%!'+*%$)%!D!/%55(,+3!$+*!+&+4$)(3!-(#!1#%!&)'1%2)(#+!5)!-/%&&+!"h!&)!$(#+!/B)#5)-%2)(#+!%//B)4$)+7(!5+//%!-)-/(0(&0%4)5+!Ya#5(g%#!xZG!%!4%77)(*!*%7)(#+3!%//(*%3!?!#+-+&&%*)%!/%!6)($&)%8!"#0%'')3!'*%4)'+!/B%#%/)&)!5+/!&+5)4+#'(!+5!)/!:1%5*(!-/)#)-(!?!&(&'%#2)%/4+#'+!)4$(&&)6)/+!-%$)*+!:1%/+!&)%!)/!/),+//(!5)!-(4$*(4)&&)(#+8!E%!&(/%!&)'1%2)(#+!)#!-1)!&)!$1N!+,)'%*+!/%!6)($&)%!?!:1%#5(!,)!&)%!1#%!&)'1%2)(#+!5)!-(4$*(4)&&)(#+!7+#+*%/+!+/+,%'%!Y+&G!&'%'(!1*+4)-(Z8!!

O+46*%!-.+!)/!/'-$+(*$%"#$)3')/$+(#'%()Y\+//\+$'xZ!!%66)%!1#%!$+*-+#'1%/+!5)!&1--+&&)!$%*%7(#%6)/+!%!:1+//%!5+//%!-)-/(0(&0%4)5+!#+)!-%&)!5)!#+0*)'+!/1$)-%!)#!-/%&&+!"h3!-(#!)/!,%#'%77)(!5)!+00+'')!-(//%'+*%/)!4(/'(!4+#(!7*%,)8!H+*!:1+&'(3!/+!1/')4+!/)#++!71)5%!&177+*)&-(#(!5)!'+#'%*+!)#!$*)4%!6%''1'%!-(#!:1+&'(!0%*4%-(!$*)4%!5)!$%&&%*+!+,+#'1%/4+#'+!%//%!-)-/(0(&0%4)5+8!

!

!

!

!

!

!

!

!

!

!

!

!

•  Classe VI: Glomerulonefrite sclerosante •  Ottico: Sono caratteristiche la sclerosi glomerulare avanzata, fibrosi

interstiziale, atrofia tubulare, che sono tutte manifestazioni di danno renale irreversibile. Le aree di proliferazione sono rare o assenti.

•  Manifestazioni cliniche: L’insufficienza renale è invariabilmente presente e di solito non risponde alla terapia.

World Health Organization Classification of Lupus Nephritis

Page 50: sbobinature nefro_0 - SkyDrive

!

!

!

!

Crioglobulinemia Le crioglobuline sono immunoglobuline che precipitano alle basse temperature.

La crioglobulinemia può essere associate con una particolare malattia (linfoma, malattia autoimmune, malattia infettiva) o può essere idiopatica ed allora è denominata crioglobulinemia essenziale. In base alla composizione, si distinguono tre tipi di crioglobulinemia:

!  Tipo I, o crioglobulinemia semplice, dovuta ad una Ig monoclonale, di solito una IgM o una IgG.

!  Tipo II e tipo III o crioglobulinemia mista, che contengono un fattore reumatoide, di solito una IgM, che si complessa con il frammento Fc di Ig policlonali. A sua volta, il fattore reumatoide può essere monoclonale (tipo II), o policlonale (tipo III).

Fisiopatologia: E’ una malattia da immunocomplessi. I pazienti hanno depositi intravscolari di Ig e bassi livelli di complemento. La crioprecipitazione in vivo determina trombosi delle piccole arterie e dei capillari alle estremità (gangrena) ed a livello glomerulare (IRA), nonché iperviscosità.

Prevalenza: la prevalenza della crioglobulinemia mista esenziale è di circa 1 caso su 100.000. Le frequenze relative sono: tipo I 25%, tipo II 25%, e tipo III 50%. Una positività per la crioglobulinemia (50-60% dei casi) si ritrova nei soggetti con infezione da HCV. Storia clinica

Le manifestazioni più tipiche dei tipi II e III sono artralgie ed artriti delle interfalangee prossimali, metacarpofalangee, ginocchia ed anche; malattia renale e lesioni vascolari purpuriche. In particolare il tipo II si associa con elevatissima frequenza ad interessamento renale ed infezione da HCV. La varie manifestazioni hanno la seguente frequenza:

!  Porpora, necrosi distale, orticaria, ulcerazioni, debolezza: 55-100% !  Manifestazioni articolari: 35-72% !  Coinvolgimento renale: 8-57% !  Fenomeno di Raynaud: 28-50% !  Parestesie e neuropatia periferica: 10-30% !  Dolore addominale: 2-22% !  Acrocianosi: 9% !  Emorragie: 7% !  Trombosi arteriolare: 1% La prognosi dipende in genere dalla malattia di base, ma peggiora quando c’è interessamento renale, con una sopravvivenza che varia dal 60% a 5 anni al 30% a 7 anni. La morbilità della crioglobulinemia è legata soprattutto alle trombosi arteriosa ed alla malattia renale.

Page 51: sbobinature nefro_0 - SkyDrive

H%'(/(7)+!*+#%/)!5%!5+$(&)'(!5)!$%*%$*('+)#+!

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

< \(4$(#+#'+!X!4(/'(!+/+,%'%!Y&($*%''1''(!&+!"7^!+5!"7MZ!< H*('+)#1*)%!5)!q+#-+<r(#+&!:1%#')'%'),%!+/+,%'%!< !I<4)-*(7/(61/)#%!+/+,%'%!< "$+*-%/-+4)%!< H*+&+#2%!5)!/+&)(#)!&-.+/+'*)-.+!< "$+*-%/-+4)%!

"#!-%&(!5)!-(4$(#+#'+!4(#(-/(#%/+!%5!"7X3!&)!$1N!%,+*+!D!$)F!-.+!1#B+,(/12)(#+!)#!4)+/(4%!D!/B+,(/12)(#+!)#!/"-,$&%$C1%'*(/'")3')k"%3(*0#,$/3!1#%!&)#5*(4+!-%*%''+*)22%'%!5%//+!4%#)0+&'%2)(#)!5%!)$+*,)&-(&)'>3!5(,1'+!%//%!$*+&+#2%!5+//+!7*(&&+!"7X!)#!-)*-(/(8!

_%##)!`+#%/)!

"/!*+#+!#(#!*)+&-+!(,,)%4+#'+!%!*)%&&(*6)*+!%!/),+//(!'161/%*+!'1''+!:1+&'+!$*('+)#+!-.+8!a&&+#5(!5)!$)--(/+!5)4+#&)(#)3!$(&&(#(!0)/'*%*+8!E+!$*('+)#+3!)#(/'*+3!&)!$(&&(#(!5+$(&)'%*+!%#-.+!%!/),+//(!5+//%!Xq!-%$)//%*+3!%/'+*%#5(!-(&e!)/!0)/'*(!7/(4+*1/%*+8!E+!$(&&)6)/)'>!5)!5%##(!*+#%/+!&(#(G!

!

!

Eziologia •  Sindrome di Fanconi: E’ caratterizzata da una disfunzione del tubulo

prossimale che determina perdita di fosfato, glucosio, amminoacidi e bicarbonati dai tubuli. Può trattarsi di una malattia ereditaria (nei bambini) o acquisita, ed è allora associata con una paraproteinemia.

•  Malattia da depositi di catene leggere: E’ una malattia sistemica causata da un’iperproduzione e deposizione extracellulare di catene leggere monoclonali. I depositi sono granulari e non formano fibrille e sono negative alla colorazione per il rosso Congo. I depositi sono dovuti alla regione costante delle immunoglobuline, e determinano un rilascio di TGF-beta da parte delle cellule mesangiali che detrmina rilascio di proteine della matrice extracellulare e sclerosi renale.

•  Rene da mieloma: oltre il 50% dei pazienti affetti da mieloma muore di insufficienza renale, ma solo una parte di essi ha effettivamente un rene da mieloma, nel quale cilindri di proteine ostruiscono i tubuli distali ed i dotti collettori, la proteina di Bence-Jones svolge un’azione tossica sulle cellule tubulari, si riduce il flusso renale ed il filtrato glomerulare, l’ipercalcemia e la disidratazione peggiorano il danno renale.

Page 52: sbobinature nefro_0 - SkyDrive

!

!

Amiloidosi L’amiloide non è una singola sostanza ma una famiglia di glicoproteine complesse a composizione variabile, con una comune configurazione a beta-pleated sheet alla diffrazione a raggi x e una birifrangenza

verde se colorata con Rosso Congo.

Sono stati identificati due tipi principali di amiloide: •  Amiloide AA. La componente principale è una proteina di 76 amminoacidi

senza nessuna relazione con le immunoglobuline. Questo tipo di amiloidosi è secondaria a malattie sistemiche croniche come l’artrite reumatoide, la sifilide, l’osteomielite cronica e le febbre familiare del Mediterraneo.

•  Amiloide AL. Le catene leggere delle immunoglobuline sono il maggior costituente dell’amiloide AL e si trovano nei pazienti con amiloidosi primitiva o nel mieloma multiplo (6-24%). In una rilevante quota di pazienti con amiloidosi primitiva si osserva una discrasia plasmacellulare nel midollo, catene leggere nel siero, e proteinuria di Bence-Jones.

•  Il meccanismo di formazione dell’amiloide rimane sconosciuto. Studi su modelli animali ed in vitro suggeriscono che nell’amiloidosi secondaria, una cronica stimolazione dei monociti da parte della IL-1 induca il fegato a produrre una proteina precursore denominata amiloide sierica, che viene poi degradata dai macrofagi con generazione delle proteine fibrillari caratteristiche dell’amiloide. Sebbene non si conoscano eventi simili per l’amiloidosi AL, si ritiene che anch’essa venga generata dai macrofagi.

Storia clinica

–  I pazienti possono presentarsi con i sintomi della malattia sotostante e/o con i sintomi della malattia renale associata.

Debolezza e letargia Persita di peso, anoressia Dolore osseo, fratture Neuropatia periferica

–  Sintomi di IR. Edema, dispnea. –  Sintomi della Sindrome di Fanconi si verificano nel 30% dei

pazienti con proteinuria da catene leggere (glicosuria, aminoaciduria, fosfaturia, lisozimuria, e acidosi tubulare prossimale).

–  Assenza di sintomi: Una funzione renale normale si osserva nel 10-40% dei pazienti.

–  Sindrome nefrosica: Si verifica nel 30% dei pazienti. –  Poliuria e polidipsia –  Infezioni ricorrenti

Page 53: sbobinature nefro_0 - SkyDrive

!

!

!

!

!

!

!

Prognosi

•  La prognosi è legata alla malattia sottostante. L’insufficienza renale è più frequente nella malattia da catene leggere. L’insufficienza renale acuta si osserva nell’8-30% e l’insufficienza renale cronica nel 30-60% dei casi.

Gammopatia monoclonale benigna: solo l’1-2% dei pazienti sviluppa IR, alcuni hanno lieve proteinuria ed ematuria.

Malattia da depositi di catene leggere: La prognosi non è buona e la morte è spesso dovuta ad insufficienza cardiaca. La sopravviveza è 90% ad 1 anno e 70 % a 5 anni, e la sopravvivenza renale dopo chemioterapia (ie, with melphalan and prednisone), del 67% e 37% ad 1 e 5 anni rispettivamente.

Mieloma multiplo: Le infezioni e l’IR sono le principali cause di morte. La prevalenza di IR è del 14% nel mieloma ad IgG, 33% ad IgA, 60% ad IgD.

Amiloidosi: La sopravvivenza nei pazienti con amiloidosi AL è del 50% a meno di due anni. Nei pazienti trattati (melphalan e prednisone) la sopravvivenza è del 78% a 5 anni contro il 7% dei non trattati.

Il Rosso Congo è sicuramente considerato la colorazione più attendibile a porre diagnosi di Amiloide glomerulare e vascolare L'amiloide appare al microscopio ottico come una sostanza extracellulare amorfa, eosinofila, PAS negativa o debolmente positiva.

Page 54: sbobinature nefro_0 - SkyDrive

X%/%'')+!'161/()#'+*&')2)%/)!

E(!&$%2)(!)#'+*&')2)%/+!#(#!*%$$*+&+#'%!1#(!&$%2)(!)#+*'+!4%3!-(#!/%!&1%!7+(4+'*)%!+!/%!&1%!-(4$(&)2)(#+3!?!)#!7*%5(!5)!4(5)0)-%*+!/B)#'+*&-%46)(!'*%!/+!&'*1''1*+!$%*+#-.)4%/)!-.+!+&&(!&+$%*%!+!&(&')+#+!&'*1''1*%/4+#'+!7*%2)+!%//+!0)6*+!-(//%7+#+!+5!%//%!&(&'%#2%!0(#5%4+#'%/+!+!-.+!,+#7(#(!4%#'+#1'+!6+%#')!)#!-(#5)2)(#)!0)&)(/(7)-.+!(!-(4$*+&&+!)#!-(#5)2)(#)!5)!+5+4%!+!5)!0)6*(&)8!M/!/),+//(!*+#%/+3!/B)#'+*&')2)(!?!-(&')'1)'(!5%)!&+71+#')!+/+4+#')G!

!

L1)#5)3!/B)#'+*&')2)(!&,(/7+!5),+*&+!01#2)(#)!4(/'(!)4$(*'%#')3!'*%!-1)G!

< k1#2)(#+!+#5(-*)#%!< k1#2)(#+!5)!*+7(/%2)(#+!5+/!0/1&&(!&%#71)7#(!< k1#2)(#+!&'*1''1*%/+!5)!&(&'+7#(!< O)#'+&)!5+//%!4%'*)-+!+g'*%-+//1/%*+!< k1#2)(#+!)441#(/(7)-%!

EB)#'+*&')2)(!$1N!+&&+*+!)#'+*+&&%'(!5%!"%#(,"2'$*')6"#$%$&'-.(!D!5(,1'+!%!-%1&+!5),+*&+!D!-.+!$(&&(#(!$*)#-)$%/4+#'+!+&&+*+!*)%&&1#'+!)#!'*+!0(#5%4+#'%/)!-%'+7(*)+!%#%'(4($%'(/(7)-.+G!

>9 ^%$&$0')A9 43(/")D9 ^'C,$0')

))

EB)#'+*&')2)(!?!1#B)4$%/-%'1*%!5)!,)'%/+!)4$(*'%#2%!$+*!)/!&)&'+4%!5+)!'161/)!*+#%/)3!$()-.[!-(#')+#+!)!,%&)!&%#71)7#)!%*'+*)(&)!

Page 55: sbobinature nefro_0 - SkyDrive

-.+!#1'*(#(!/B+$)'+/)(!'161/%*+!+!)/!&)&'+4%!5+)!5('')!-(//+''(*)C!)#(/'*+3!/B)#'+&')2)(!*+#%/+!$(&&)+5+!5+'+*4)#%'+!-%*%''+*)&')-.+!0)&)-(<-.)4)-.+!)#5)&$+#&%6)/)!$+*!/%!-%$%-)'>!5)!-(#-+#'*%*+!+!5)/1)*+!/+!1*)#+3!+!&1+!%/'+*%2)(#)!&)!*)0/+''(#(!$+*!0(*2%!5)!-(&+!&1//%!01#2)(#+!*+#%/+3!+!&$+-)0)-%4+#'+3!&1//%!,)'%/)'>!+!&1//%!01#2)(#%/)'>!5+//+!-+//1/+!'161/%*)8!"#(/'*+3!/+!%/'+*%2)(#)!)#'+*&')2)%/)!$(&&(#(!%/'+*%*+!)/!0)/'*%'(!7/(4+*1/%*+!+!%''),%*+!)/!0++56%-]!'161/(7/(4+*1/%*+8!

O+!?!,+*(!-.+!)/!5%##(!)#'+*&')2)%/+!$*)4)'),(!&)!*)0/+''+!)#!1#!5%##(!'161/%*+3!?!%#-.+!,+*(!)/!-(#'*%*)(8!T#!$*(-+&&(!$%'(/(7)-(!-.+!)#'+*+&&%!)!'161/)!&)!*)0/+''+!)#!1#!5%##(!)#'+*&')2)%/+!-.+3!%!&1%!,(/'%3!%77*%,%!)/!5%##(!'161/%*+!)#)2)%/+8!

!

E+!-+//1/+!'161/%*)3!5%##+7)%'+3!,%##(!)#-(#'*(!%5!1#%!4(5)0)-%2)(#+!5)!%&&+''(!01#2)(#%/+!-.+!$*+,+5+G!

< 406,(00'$*()3')/$%(-$%()h_S)6,(0(*#"*#')"*#'&(*')< 406,(00'$*()3')/$%(-$%()-$0#'/$%"#$,'()< U'%"0-'"#$)3')-'#$-.'*(G)+"##$,')3')-,(0-'#")< 406,(00'$*()3')/$%(-$%()3')"3(0'$*()< 8,"*0'2'$*()(6'#(%'$L/(0(*-.'/"%()

L1)#5)3!)#!:1+&'(!-(#'+&'(3!/+!-+//1/+!'161/%*)!,%##(!)#-(#'*(!%5!%$($'(&)!+!#+-*(&)3!$*(,(-%#(!/B%''),%2)(#+!5+//+!-+//1/+!)441#)'%*)+!-.+!%#5*%##(!%5!)#0)/'*%*+!/B)#'+*&')2)(!+!5+'+*4)#%#(!/B%''),%2)(#+!5+)!0)6*(6/%&')!)#'+*&')2)%/)8!b+!5+*),%!1#%!*+%2)(#+!0)6*(')-%!+!0/(7)&')-%!-.+!#(#!0%!%/'*(!-.+!*)51**+!/%!$+*01&)(#+!5+)!-%$)//%*)!-.+!#1'*(#(!)!'161/)!+3!:1)#5)3!%4$/)0)-%*+!)/!5%##(!'161/%*+!)#)2)%/+8!"!-%$)//%*)3!)#(/'*+3!+&&+#5(!4+#(!#14+*(&)!+!5)!-%/)6*(!*)5(''(3!5+'+*4)#%#(!'6(,#(*0'$*()&%$/(,1%",(3!(!&+!$*+,%/+!/B+00+''(!&1)!,%&)!%00+*+#')!7/(4+*1/%*)3!'0-.(/'")&%$/(,1%",(9))

TOSSICI ISCHEMIA INFEZIONI CRISTALLI FARMACI OSTRUZIONE

DANNO CELLULE TUBULARI

ESPRESSIONE ATG HLA

FUNZIONE PRESENTAZIONE

ATG

RILASCIO DI CITOKINE PROTEINASI, MOLECOLE DI ADESONE E FATTORI

DI CRESCITA

RECLUTAMENTO ED ATTIVAZIONE

LINFOCITI T E MACROFAGI

RECLUTAMENTO ED ATTIVAZIONE

FIBROBLASTI

ATROFIA TUBULARE

NECROSI APOPTOSI

TRANSIZIONE EPITELIO-

MESENCHIMALE

INFILTRATI INTERSTIZIALI

FIBROSI INTERSTIZIALE

DISFUNZIONE TUBULARE

PERFUSIONE CAPILLARE

Page 56: sbobinature nefro_0 - SkyDrive

!

!

"!'161/)!$(&&(#(!+&&+*+!5%##+77)%')!%#-.+!5%/!/(*(!)#'+*#(!$+*!/B+00+''(!5)!-)/)#5*)!+!-*)&'%//)!5)!,%*)%!#%'1*%G!)#!:1+&'(!-%&(!&)!,)+#+!%!5+'+*4)#%*+!(&'*12)(#+!'161/%*+3!-(#!%14+#'(!5+//%!$*+&&)(#+!'161/%*+!%!4(#'+!+!-(#&+71+#'+!%'*(0)%!'161/%*+8!L1+&'(3!$%*%//+/%4+#'+3!&)!*)0/+''+!%#-.+!&1/!7/(4+*1/(!%!4(#'+3!-%1&%#5(#+!)/!5%##(8!

"#!5+0)#)'),%3!:1)#5)3!)/!5%##(!)#'+*&')2)%/+!+5!)/!5%##(!'161/%*+!$(&&(#(!*)0/+''+*&)!&1//%!01#2)(#+!5)!0)/'*%2)(#+!+3!:1)#5)3!5+'+*4)#%*+!1#%!6(,3'#")6,$&,(00'7"!5)!#+0*(#)!+3!:1)#5)3!1#(!&'%'(!5)!'*01++'-'(*2"),(*"%()-,$*'-"9))

!

=(+,'#')R*#(,0#'2'"%')

E+!#+0*)')!)#'+*&')2)%/)!&)!5),)5(#(!)#!"-1#(!+!-,$*'-.(!%!&+-(#5%!5+/!5+-(*&(!-/)#)-(8!_%/!$1#'(!5)!,)&'%!+')(/(7)-(3!)#,+-+3!+&&+!$(&&(#(!+&&+*+G!

>9 R3'$6"#'-.()A9 V")+",/"-')()#$00'-')D9 <(-$*3",'()")/"%"##'()0'0#(/'-.()B9 R*+(##'7()?9 V"),'&(##$)-,$*'-$)3'),(*()#,"6'"*#"#$)

E+!0(*4+!&+-(#5%*)+!%!4%/%'')+!&)&'+4)-.+!)#-/15(#(!-+*'%4+#'+!/+!4%/%'')+!%1'()441#)3!-(4+!)/!EaO3!/%!7*%#1/(4%'(&)!5)!t+7+#+*3!/%!4)-*($(/)%#7)()'+3!/%!&)#5*(4+!5)!Opy7*+#3!4%!%#-.+!4%/%'')+!(#-(+4%'(/(7)-.+3!-(4+!)/!4)+/(4%!41/')$/(!+!/+!#+($/%&)+!/)#0($*(/)0+*%'),+!-*(#)-.+C!1#%!-/%&&)0)-%2)(#+!+2)(/(7)-%!$)F!%$$*(0(#5)'%!$1N!+&&+*+!/%!&+71+#'+G!

CARICO DISTALE DI ACQUA E SOLUTI

FLOGOSI, FIBROSI INTERSTIZIALE

OSTRUZIONE TUBULARE

CRISTALLI, CILINDRI, ECC

AB INTRINSECO

AB ESTRINSECO

PRESSIONE TUBULARE

DANNO GLOMERULARE

ATROFIA TUBULARE

RESISTENZE VASCOLARI

NUMERO E CALIBRO

CAPILLARI

VASI AFFERENTI AI GLOMERULI

ISCHEMIA GLOMERULARE

IPERTENSIONE GLOMERULARE

ATROFIA TUBULARE

(TCP, BRANCA SPESSA ASCENDENNTE HENLE

RIASSORBIMENTO DI ACQUA E SODIO

VASI EFFERENTI DAI GLOMERULI FEEDBACK

TUBULO GLOMERULARE

RILASCIO RENINA PRODUZ. ANGIOT II

RELATIVA VASODILATAZ. ART.

GLOM. EFF.

FILTRAZIONE GLOMERULARE

Page 57: sbobinature nefro_0 - SkyDrive

!

E+!0(*4+!-%1&%'+!5%!+",/"-')&(#(!7+#+*%/4+#'+!"-1#(C!)!$*)#-)$%/)!0%*4%-)!)4$/)-%')!&(#(G!

<!S*#'C'$#'-'Q!$+#)-)//)#+3!-+0%/(&$(*)#+3!%4)#(7/)-(&)5)-)3!&1/0%4)5)-)3!*)0%4$)-)#%3!-.)#(/(#)-)!<!V'1,(#'-'G!')%2)5)-)3!01*(&+4)5+!!<!^S=<G!0+#($*(0+#+3!)#5(4+'%-)#%3!5)-/(0+#%-3!MOM!<!S*#'-$*71%0'7"*#'G!-%*6%4%2+$)#%3!5)0+#)/)5%#'()#%3!0+#(6%*6)'%/!<!S%#,'G!%//($1*)#(/(3!*%#)')5)#%3!(4+$*%2(/(3!-%$'($*)/3!%2%')($*)#%3!)#'+*0+*(#+!

!

=(+,'#')#1C1%$'*#(,0#'2'"%')-,$*'-.()

_%/!$1#'(!5)!,)&'%!-/%&&)0)-%'),(!&)!5+0)#)-(#(G!

< 8R=)!,'/",'(3!&+!)#)2)%#(!$*)4%*)%4+#'+!-(4+!$%'(/(7)%!5+//B)#'+*&')2)(!+!5+/!&)&'+4%!5+)!'161/)3!-()#,(/7+#5(!/+!*+&'%#')!%*++!)#!1#!&+-(#5(!4(4+#'(8!!

< 8R=)<(-$*3",'(3!&+!)/!$*(-+&&(!$%'(/(7)-(!)#)2)%!#+/!0'0#(/")7"0-$%",(G)&%$/(,1%",()$)3(%%()/"&&'$,')7'()(0-,(#,'-'!+!&(/(!)#!1#!1#!&+-(#5(!4(4+#'(!&)!+&'+#5+!%)!'161/)!+!%//B)#'+*&')2)(8!!

"#!%/-1#+!4%/%'')+3!'1''%,)%3!)/!-()#,(/7)4+#'(!$1N!+&&+*+!&)41/'%#+(8!

!

\%*%''+*)&')-.+!-/)#)-.+!

_%/!$1#'(!5)!,)&'%!-/)#)-(3!)/!:1%5*(!&)!%*')-(/%!)#!5),+*&)!%&$+'')8!

>9 V(#(,'$,"/(*#()6,$&,(00'7$)3(%%")+1*2'$*(),(*"%()

IDIOPATICA IDIOPATICA – ENDEMICA (nefropatia dei Balcani) EREDITARIE: nefronoftisi, malattia cistica midollare, nefropatia iperuricemica familiare giovanile, ADPKD, ARPKD INFEZIONI: pielonefrite cronica, pielonefrite xantogranulomatosa, malacoplachia, TBC. FARMACI E TOSSICI: analgesici, acido aristolochico, litio, ciclosporina, tacrolimus, indinavir, cisplatino. METALLI PESANTI: piombo, cadmio, arsenico, mercurio, oro, uranio. RADIAZIONI, ONDE D’URTO ALTERAZIONI METABOLICHE: iperuricemia, ipopotassiemia, ipercalcemia, iperossaluria, cistinosi. MALATTIE AUTOIMMUNI: LES, sindrome di Syogren, sarcoidosi, sindrome di Wegener ed altre vasculiti. OSTRUZIONE CRONICA, REFLUSSO VESCICO-URETERALE MALATTIE EMATOLOGICHE: mieloma, leucemie, linfomi, anemia falciforme, emoglobinuria parossistica notturna MALATTIE VASCOLARI: malattia renale aterosclerotica RIGETTO CRONICO DI TRAPIANTO RENALE SECONDARIA A MALATTIE GLOMERULARI PROGRESSIVE:

CAUSE

Page 58: sbobinature nefro_0 - SkyDrive

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

A9 <(3'/(*#$)1,'*",'$)&(*(,"%/(*#()*$*)0'&*'+'-"#'7$)

"/!&+5)4+#'(!1*)#%*)(!#(#!%**+-%!1#!-(#'*)61'(!&)7#)0)-%'),(!%//%!5)%7#(&)3!+--+''(!-.+!#+//+!0(*4+!%-1'+!&1!6%&+!%//+*7)-%3!$+*-.[!)#!:1+&'+!0(*4+!$1N!+&&+*+!+,)5+#2)%'%!/%!$*+&+#2%!5)!#14+*(&)!+(&)#(0)/)3!-(&%!%66%&'%#2%!')$)-%8!

D9 !,$#('*1,'")#1C1%",(G)l>)&E3'()

E%!$*('+)#1*)%!'161/%*+!?!4(/'(!0*+:1+#'+!+5!?!)#5)-+!5+/!5%##(!'161/%*+G!&)!*)'*(,%#(!#+//+!1*)#+!$*)#-)$%/4+#'+!$*('+)#+!5)!(*)7)#+!'161/%*+!+!$*('+)#+!5%/!6%&&(!$+&(!4(/+-(/%*+3!)#5)-+!5)!)#-%$%-)'>!5+/!'161/(!$*(&&)4%/+!5)!*)%&&(*6)*+!/+!$*('+)#+!%!6%&&(!$+&(!4(/+-(/%*+!-.+!0)/'*%#(!#(*4%/4+#'+8!!

B9 V'0+1*2'$*()#1C1%",()6,$00'/"%()

E%!5)&01#2)(#+!5+/!'161/(!$*(&&)4%/+!&)!$*+&+#'%!-(#!)/!5+0)-)'!5)!*)%&&(*6)4+#'(!5+//+!&(&'%#2+!#(*4%/4+#'+!*)%&&(*6)'+!%!:1+&'(!/),+//(G!

< ^/)-(&1*)%!< T*)-(&1*)%!< "$+*0(&0%'1*)%!< M4)#(%-)51*)%!< q)-%*6(#%'1*)%!Y!!S-'3$0')#1C1%",()6,$00'/"%(J!< "$+*]%/)1*)%!

EB)#&)+4+!5)!:1+&')!5)0+'')!-(&')'1)&-+!/%!0'*3,$/()3')^"*-$*'8!_5"-'3$)-.()0').")'*)a1(0#')-"0')i)1*5"-'3$0')'6$-%$,(/'-"3!-.+!5+*),%3!(/'*+!-.+!5%//%!$+*5)'%!5)!6)-%*6(#%')3!%#-.+!5%//%!*)5(''%!%44(#)(7+#+&)!+!5%//%!5)&01#2)(#+!'161/%*+!5)&'%/+!Y)#-%$%-)'>!5)!%-)5)0)-%*+!/%!$*+<1*)#%Z8!!

a&+4$)!5)!$%'(/(7)+!)#!-1)!/%!5)&01#2)(#+!'161/%*+!$*(&&)4%/+!&)!$*+&+#'%!-(#!$%*')-(/%*+!0*+:1+#2%G!/'(%$/"G)_4<G)*(+,$6"#'")3")/(#"%%')6(0"*#')I!CG)h&G);3JG)-'0#'*$0'G),'&(##$)-,$*'-$)3')#,"6'"*#$9))

?9 V'0+1*2'$*()3(%)#1C1%$)3'0#"%()

"/!'161/(!5)&'%/+!&,(/7+!#14+*(&+!01#2)(#)!5)!0(#5%4+#'%/+!)4$(*'%#2%8!d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b(#!&(/(3!4%!)/!'161/(!5)&'%/+!?!+&&+#2)%/+!%#-.+!#+/!$*(-+&&(!5)!-(#-+#'*%2)(#+!5+//+!1*)#+3!)#!:1%#'(!/+!&1+!

Page 59: sbobinature nefro_0 - SkyDrive

-+//1/+!)#'+*,+#7(#(!#+/!$*(-+&&(!5)!*)-)*-(/(!5+//B1*+%3!+/+4+#'(!+&&+#2)%/+!$+*!$('+*!*+7(/%*+!&+-(#5(!#+-+&&)'>!/B(&4(/%*)'>!5+//B)#'+*&')2)(!4)5(//%*+!*+#%/+3!$*+4+&&%!+&&+#2)%/+!$+*!0%*!,%*)%*+!/%!-(#-+#'*%2)(#+!5+//+!1*)#+8!EBM_l3!$()3!0%!)/!*+&'(!4(51/%#5(!/B+&$*+&&)(#+!5)!%-:1%$(*)#+!+!-%**)+*&!$+*!/B1*+%!%/!/),+//(!5+/!'161/(!5)&'%/+!+!5+)!5('')!-(//+''(*)8!

E%!5)&01#2)(#+!5+)!5('')!-(//+''(*)!&)!4%#)0+&'%!-(#G!

< U'3$##")"//$*'$&(*(0')! )S-'3$0')#1C1%",()3'0#"%()< !(,3'#")3')0"%()I<"%#)T"0#'*&)0]*3,$/(J)< R6$0#(*1,'")< R6(,W"%'(/'")< !$%'1,'")

E%!-(4$(#+#'+!'161/%*+!5)&'%/+!&)!$*+&+#'%!&($*%''1''(!)#!:1+&'+!$%'(/(7)+G!

< _4<)< <\m&,(*)< S/'%$'3$0')< =9)$0#,1##'7")< U(*()6$%'-'0#'-$)< R6(,-"%-(/'")< =(+,'#()'*#(,0#'2'"%()"-1#")3")+",/"-')

)

Z9 V'0+1*2'$*()/'3$%%",()()6"6'%%",()

M#-.+!)#!:1+&'(!-%&(!)/!:1%5*(!?!5(4)#%'(!5%//%!$+*5)'%!5)!&%/+!+!5%//B)#-%$%-)'>!5)!-(#-+#'*%*+!/+!1*)#+3!4+--%#)&4(!#+/!:1%/+!)!5('')!-.+!5+-(**(#(!#+//%!4)5(//%*+!&,(/7(#(!1#!*1(/(!-*1-)%/+8!!M/-1#+!$%'(/(7)+G!

< b8!(&'*1''),%!< `+#+!$(/)-)&')-(!< H)+/(#+0*)'+!%-1'%!< b+0*($%')%!5%!%#%/7+&)-)!< b+-*(&)!$%$)//%*+!)#!-(*&(!5)!5)%6+'+!4+//)'(!

!

f9 S*(/'")06,$6$,2'$*"#")"%)&,"3$)3')3'0+1*2'$*(),(*"%()

L1+&'(!$+*-.?!#+//+!#+0*($%')+!)#'+*&')2)%/)!/+!-+//1/+!$*(51''*)-)!5)!aH9!&(#(!$*)4)'),%4+#'+!-()#,(/'+3!)#5)$+#5+#'+4+#'+!5%//%!01#2)(#+!*+#%/+!*+&)51%8!!

!

=(+,$6"#'")3")"*"%&(0'-')

E%!#+0*($%')%!5%!%#%/7+&)-)!?!1#%!0(*4%!5)!#+0*)'+!'161/()#'+*&')2)%/+!-(#!-%*%''+*)&')-.+!$%*')-(/%*)8!d!&'%'%!5+&-*)''%!)#,%*)%6)/4+#'+!)#!)#5),)51)!-(#!&'(*)%!5)!+$,#()-$*01/$)3')"00$-'"2'$*')3')"*"%&(0'-'Q)

< ^(*"-(#'*")n)S<S)< S<S)n)^(*"-(#'*")n);$3('*")< 4--o)

Page 60: sbobinature nefro_0 - SkyDrive

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

!

aB!$*(6%6)/+!-.+!)/!5%##(!&+/+''),(!5+//%!$%$)//%!5)$+#5%!5%!1#!7*%5)+#'+!5)!-(#-+#'*%2)(#+!-(*')-(4)5(//%*+!5+/!4+'%6(/)'%!5+//%!0+#%-+')#%3!)/!$%*%-+'%4(/(8!/%!-(#-(4)'%#'+!%&&1#2)(#+!5)!%&$)*)#%!%6(/)&-+!/%!$*(512)(#+!5)!$*(&'%7/%#5)#+!*+#%/)3!:1)#5)!,)+#+!%!5+'+*4)#%*+!-%*+#2%!5)!0%''(*)!,%&(5)/%'%#')!-.+!$('*+66+*(!4%#'+#+*+!)/!0/1&&(!5+//%!4)5(//%*+8!!

E%!01#2)(#+!*+#%/+!,)+#+!$+*51'%!$*(7*+&&),%4+#'+8!O"*'+(0#"2'$*')6,(-$-')3(%%")*(+,$6"#'")3")"*"%&(0'-')0$*$Q)

< <'*3,$/()3")3$%$,()-,$*'-$!\(#5)2)(#%!/B%&&1#2)(#+!5)!%#%/7+&)-)8!

< V'0#1,C')&"0#,$*'*#(0#'*"%')H*(,(-%')!5%7/)!%#%/7+&)-)!&'+&&)cv!

< S*(/'")06,$6$,2'$*"#")"%)&,"3$)3')RU)< R6(,W"%'(/'")

M#-.+!:1+&'%!?!&$*($(*2)(#%'%!%//%!5)&01#2)(#+!*+#%/+3!:1+&'(!$+*-.[!)!'161/)!5)&'%/)!&(#(!-()#,(/')!$*)4)'),%4+#'+8!

< !'1,'")0#(,'%()< S-'3$0')#1C1%",()3'0#"%()

_+0)-)'!5)!+&-*+2)(#+!5)!$*('(#)!+!7+#+*%2)(#+!5)!6%&)C!)#&100)-)+#'+!%44(#)(7+#+&)8!H1N!-(#'*)61)*+!%//(!&,)/1$$(!5)!#+0*(-%/-)#(&)8!

< R6$0#(*1,'")H+*-.[!)/!'161/(!5)&'%/+!+!/%!4)5(//%*+!&(#(!)!&)')!$*)#-)$%/)!-.+!($+*%#(!#+//%!*+7(/%2)(#+!5+//%!-(#-+#'*%2)(#+!5+//+!1*)#+8!

< ;$%'-"),(*"%()

LESIONI RENALI ASSOCIATE AD ABUSO DI ANALGESICI

CORTICALE - normale

CORTICALE - normale

CORTICALE

PAPILLA E MIDOLLARE INTERNA – alterazioni focali: sclerosi capillare, necrosi focali cellule interstiziali, branche sottili Henle, vasa recta

PAPILLA E MIDOLLARE INTERNA– necrosi ed atrofia progressive

PAPILLA – atrofia e necrosi totale

MIDOLLARE ESTERNA – normale

MIDOLLARE ESTERNA – comparsa alterazioni focali

Atrofia in corrispondenza della papilla necrotica

Ipertrofia (raggi midollari risparmiati)

Stage I

Stage II

Stage III

Page 61: sbobinature nefro_0 - SkyDrive

\%1&%'%!5%//B(--%&)(#%/+!)#-1#+%4+#'(!5)!0*%44+#')!5)!$%$)//%!#+-*(')-%!#+//+!,)+!+&-*+'*)-)8!

< O$3(0#")6,$#('*1,'")#1C1%",()< O'-,$E/"-,$(/"#1,'")

R)0(&*')#",3'7'!&(#(!)#!7+#+*%/+!'1'')!:1+//)!5+//B)#&100)-)+#2%!*+#%/+!-*(#)-%3!0)#(!%//(!&,)/1$$(!5+//%!&)#5*(4+!1*+4)-%8!V%/,(/'%3!&)!$1N!%,+*+!+4%'1*)%!-%1&%'%!5%//(!&,)/1$$(!5)!1#!-%*-)#(4%!'*%#&)2)(#%/+3!+,+#'(!$)1''(&'(!0*+:1+#'+!)#!:1+&')!$%2)+#')8!!

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

!

aB!-(#'*(,+*&(!)/!*1(/(!5)!%/'*)!kMbO!)#!:1+&'%!$%'(/(7)%8!"#!7+#+*%/+3!&)!*)')+#+!-.+G!

< R)^S=<)6$00"*$)"&&,"7",()'%)a1"3,$)3(%%")*(+,$6"#'")3")^S=<)< R)^S=<)6$00"*$)"&&,"7",()0'-1,"/(*#()a1"%0'"0')*(+,$6"#'")-,$*'-"3!

$('+#5(!-%1&%*+!:1%5*)!5)!)#&100)-)+#2%!*+#%/+!%-1'%3!&($*%''1''(!%!-%1&%!5+//%!/(*(!-%$%-)'>!5)!)#)6)*+!/%!&)#'+&)!5+//+!$*(&'%7/%#5)#+8!O(#(!)#(/'*+!)$+*]%/)+4)22%#')8)

< !$00"*$)'*)"%-1*')-"0')-"10",()1*")0$,#")3')*(+,'#()-,$*'-")

)

)

De Broe ME, NEJM 1998; 38 (7): 446

CRITERI DIAGNOSTICI DI NEFROPATIA DA ANALGESICI IN PAZIENTI CON INSUFFICIENZA RENALE CRONICA (TC DIRETTA)

Dimensioni diminuite = A+ B < 103 mm (M) o < 96 mm (F). Contorni bozzuti = almeno 3 incisure

Page 62: sbobinature nefro_0 - SkyDrive

=(+,$6"#'")3")6'$/C$)

"/!$)(46(!?!1#%!'(&&)#%!16):1)'%*)%!+!&($*%''1''(!(--1$%2)(#%/+8!b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

< a&$(&)2)(#+!-*(#)-%!%!6%&&+!:1%#')'>!5)!$)(46(!< a&$(&)2)(#+!%-1'%!)#'+*4)''+#'+!%5!+/+,%'+!:1%#')'>!5)!$)(46(!

<$,&(*#')5)!)#'(&&)-%2)(#+G!vernici, saldature, processi di fusione, carburanti, fumi industriali, proiettili ritenuti, batterie, whiskey di contrabbando, additivi per vini e farmaci, ecc.

Categorie a rischio: Lavoratori nella produzione di vernici e ceramiche, costruzione di auto, demolizione di edifici, produzione di carburanti, impiegati in fonderie, in miniere, in stamperie, in poligoni di tiro, bambini (picacismo)!

L1%5*(!%#%'(4($%'(/(7)-(!

"/!$)(46(3!-(4+!&)!?!5+''(3!'+#5+!%5!%--141/%*&)!)#!&+5+!)#'*%-+//1/%*+3!+!)/!&+74+#'(!$)F!)#'+*+&&%'(!?!/BOK!5+/!#1C1%$)6,$00'/"%(9!E+!%/'+*%2)(#)!,)&1%/)22%6)/)!$*+-(-+4+#'+!&(#(G!

< !,(0(*2")3')'*-%10'$*')'*#,"*1-%(",')< U'&$*+'"/(*#$)/'#$-$*3,'"%()< ;$,6')3(*0')%'0$0$/'"%')

"#!:1+&'%!$*)4%!0%&+3!&1/!$)%#(!-/)#)-(3!/+!%/'+*%2)(#)!$)F!0*+:1+#')!&(#(!'6(,1,'-(/'"!Y5%!5+0)-)'!5)!&+-*+2)(#+!5)!%-)5(!1*)-(Z3!&%'-$01,'")+!"/'*$"-'31,'"3!5%!5)&01#2)(#+!5+/!'161/(!Y-(41#:1+!$)F!*%*+Z8!"#!%/-1#)!$%2)+#')!&)!$(&&(#(!)#&'%1*%*+!,+*)!+!$*($*)!a1"3,')&$##$0'9)!

L1+&'+!%/'+*%2)(#)!$*+-(-)!&(#(!&+71)'+3!#+/!'+4$(3!5%//(!&,)/1$$(!5)!1#%!*(+,'#()'*#(,0#'2'"%()-(#'*%55)&')#'%!5%G!

< O",-"#")+'C,$0')'*#(,0#'2'"%()< S#,$+'")#1C1%",()

E%!0)6*(&)!-(&e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

M//%!0)#+3!)/!:1%5*(!?!5(4)#%'(!5%//B)#&100)-)+#2%!*+#%/+3!%--(4$%7#%'%!5%!0*+:1+#')!%''%--.)!7(''(&)!+5!)$+*'+#&)(#+!%*'+*)(&%8!!

!

Page 63: sbobinature nefro_0 - SkyDrive

_)%7#(&)!!

H+*!0%*+!5)%7#(&)!(--(**+!%#2)'1''(!1#B%--1*%'%!"*"/*(0')$--16"2'$*"%(9)"/!*)/)+,(!5)!&$##")'*)"00$-'"2'$*()"3)'*01++'-'(*2"),(*"%(!?!1#!:1%5*(!-.+!5+,+!&177+*)*+!/%!#+0*($%')%!5%!$)(46(8!H()3!&)!$*(-+5+!%//%!*)/+,%2)(#+!5+)!/),+//)!5)!$)(46(!+4%')-)!+!%/!'+&'!5)!-.+/%2)(#+!-(#!a_VMG!

!

V+*%$)%!

E%!'+*%$)%!&)!%*')-(/%!)#!51+!')$)!5)!)#'+*,+#'(8!H+*!$*)4%!-(&%3!6)&(7#%!+/)4)#%*+!/%!+$*#()3')(06$0'2'$*(!%/!$)(46(8!H%*%//+/%4+#'+3!6)&(7#%!'+#'%*+!5)!4(6)/)22%*+!)!5+$(&)')!5)!$)(46(G!:1+&'(!?!&)-1*%4+#'+!0%'')6)/+!)#!-%&(!5)!)#'(&&)-%2)(#+!%-1'%3!4%!%#-.+!)#!-%&(!5)!)#'(&&)-%2)(#+!-*(#)-%!&)!$(&&(#(!(''+#+*+!('')4)!*)&1/'%')8!H+*!/%!4(6)/)22%2)(#+!&)!&(44)#)&'*%!W!7!5)!a_VM!41&-(/(!)#!K!&(44)#)&'*%2)(#)!&+'')4%#%/)8!"/!*)&1/'%'(!?!*)$(*'%*+!)!,%/(*)!5)!$)(46(!#+//+!1*)#+!#+//%!#(*4%/)'>8!!

!

=(+,$6"#'")3")%'#'$)

"!&%/)!5)!/)')(!&(#(!)4$)+7%')!#+/!'*%''%4+#'(!5+//+!0(*4+!6)$(/%*)!)#!$&)-.)%'*)%3!&($*%''1''(!-(4+!'+*%$)%!5)!4%#'+#)4+#'(3!)#!,)*'F!5+//%!&1%!+00)-%-)%!%#-(*%!)#!7*%#!$%*'+!)#&1$+*%'%8!"/!/)')(!,)+#+!0)/'*%'(!-(4$/+'%4+#'+!%!/),+//(!7/(4+*1/%*+!+!*)%&&(*6)'(!$+*!)/!iPR3!;PR!%!/),+//(!5+/!'161/(!$*(&&)4%/+8!

"/!E)')(!$1N!&(&')'1)*&)!%/!b%!)#!5),+*&)!-%#%/)!5+/!b%G!!

<!b+/!&)&'+4%!%#')$(*'(!b%Ul!#+/!'161/(!-(#'(*'(!$*(&&)4%/+!

<!b+/!&)&'+4%!5)!-('*%&$(*'(!b%<n<I\/!#+/!'*%''(!&$+&&(!%&-+#5+#'+!5+//B%#&%!5)!l+#/+!!

<!b+)!-%#%/)!+$)'+/)%/)!$+*!)/!b%!#+/!5(''(!-(//+''(*+!-(*')-%/+8!

E%!%'#'(/'")?!1#!$%*%4+'*(!-.+!5+,+!+&&+*+!%''+#'%4+#'+!4(#)'(*%'(!)#!-(*&(!5)!'+*%$)%3!-(#!/B(6)+''),(!5)!4%#'+#+*#+!)!/),+//)!'*%!P3;<W3I!4a:UE8!EB+/+,%2)(#+!+--+&&),%!5+//%!/)')+4)%!$1N!-(4$(*'%*+!'*#$00'-"2'$*()"-1#")3")%'#'$3!-.+!&)!$*+&+#'%!-(#!#%1&+%3!,(4)'(3!5)%**+%!+!'1*6+!#+1*(/(7)-.+!4)#(*)8!!

H+*!:1%#'(!*)71%*5%!/%!'(&&)-)'>!-*(#)-%!*+#%/+3!&)!%*')-(/%!)#!51+!$1#')G!

< V'"C(#()'*0'6'3$)*(+,$&(*'-$)

NEFROPATIA CRONICA DA PIOMBO

DIAGNOSI

ANAMNESI OCCUPAZIONALE ASSOCIAZIONE GOTTA-INSUFFICIENZA RENALE

LIVELLI EMATICI DI PIOMBO

Riflettono usualmente ESPOSIZIONE RECENTE

> 80 mcg/dl (adulto) > 40 mcg/dl (bambino) > 10 mcg/dl persistentemente

Suggerito sovraccarico di

Pb

TEST DI CHELAZIONE

CON (Na-Ca)EDTA

1.0 g X 2 im (intervallo 12 ore) 0.5 g x 2 ev (intervallo 12 ore) in 250 cc SG 5 %

Pburia > 650 mg nelle 24 ore successive (creat < 1.5 mg/dl) Pburia > 650 mg nelle 72 ore successive (creat > 1.5 mg/dl)

Page 64: sbobinature nefro_0 - SkyDrive

\%1&%'(!5%//B%2)(#+!5+/!/)')(3!-.+!5)&%--($$)%!%/-1#)!*+-+''(*)!5%//+!$*($*)+!$*('+)#+!^8!b+//(!&$+-)0)-(3!%/!/),+//(!*+#%/+!)/!/)')(!5)&%--($$)%!)/!*+-+''(*+!hI!5+//BM_l!5%//%!&1%!$*('+)#%!^8!!

< =(+,$6"#'")-,$*'-")3")%'#'$))

) )

E%!4%#)0+&'%2)(#+!-/)#)-%!5+//%!#+0*($%')%!5%!/)')(!?!/%!$*(7*+&&),%!5)&01#2)(#+!*+#%/+3!/+#'%4+#'+!$*(7*+&&),%!-.+!&)!$*+&+#'%!#+/!WSR!5+)!$%2)+#')3!&$+&&(!%&&(-)%'%!%!)$(&'+#1*)%!(!5)%6+'+!)#&)$)5(!#+0*(7+#)-(8!EB)#&100)-)+#2%!*+#%/+!-*(#)-%!5%!/)')(!$1N!$*(7*+5)*+!,+*&(!/B)#&100)-)+#2%!*+#%/+!'+*4)#%/+3!+!)#!7+#+*+!/B+,(/12)(#+!)4$)+7%!IP!%##)!$+*!,+*)0)-%*&)8!k%''(*)!-.+!$(&&(#(!)#5)-%*+!)/!*)&-.)(!5)!$*(7*+&&)(#+!&(#(G!

< \*+%')#)#+4)%!%//%!5)%7#(&)!< H*('+)#1*)%!< _(&+!-141/%'),%!5)!/)')(!%&&1#'%!

L1)#5)3!$)F!/1#7%!?!/%!'+*%$)%!+!$)F!+/+,%'(!?!)/!5(&%77)(3!$)F!?!$*(6%6)/+!-.+!&)!*%77)1#7%!/(!&'%5)(!5)!aO`_8!

M//%!X`"!&)!*)&-(#'*%#(!41/')$/+!4)-*(-)&')!*+#%/)!5+/!5)%4+'*(!5)!W<I!44!)#!'1''+!/+!%*++!5+//%!-(*')-%/+!+!5+//%!4)5(//%*+G!?!1#!:1%5*(!-.+!&177+*)&-+!/%!5)%7#(&)8!

!

!

!

!

!

!

!

!

NEFROPATIA CRONICA DA LITIO

FIBROSI INTERSTIZIALE CRONICA focale relativamente acellulare

ATROFIA E DILATAZIONE TUBULARE

MICROCISTI (origine da tubuli distali e dotti collettori) corticali e midollari di diametro 1-2 mm

Usuale relativo RISPARMIO dei glomeruli

Casi di GLOMERULONEFRITE A LESIONI MINIME

In pazienti con insufficienza renale (= tardivamente) frequente riscontro di GLOMERULOSCLEROSI GLOBALE o GLOMERULOSCLEROSI FOCALE SEGMENTARIA con glomerulomegalia

DANNO TUBULO INTERSTIZIALE

DANNO GLOMERULARE

T2 T2 RARE

(rapid acquisition relaxation enhancemen)

NEFROPATIA CRONICA DA LITIO (RM)

Numerose microcisti rotondeggianti del diametro di 1-2 mm in tutte le aree della corticale e della midollare renale.

Farres MT, Radiology 2003, Nov: 570

Page 65: sbobinature nefro_0 - SkyDrive

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

)

=(+,$6"#'")(*3(/'-")3(')C"%-"*')

L1+&'%!$%'(/(7)%!*+#%/+!?!&'%'%!5+&-*)''%!#+7/)!%##)!BSP!+!B;P!)#!4(/'+!%*++!6%/-%#)-.+!+!#+//Ba&'!+1*($+(8!_%/!$1#'(!5)!,)&'%!+$)5+4)(/(7)-(3!:1+&'%!$%'(/(7)%!$*+&+#'%!%/-1#+!-%*%''+*)&')-.+!4(/'(!$%*')-(/%*)G!

L)<')6,(0(*#")0$%$)'*)0#"#')C"%-"*'-'Q)K1%&",'"G)U$/"*'"G)(cLp1&$0%"7'")IK$0*'"G)<(,C'"G);,$"2'"J9)L)<$%$)'*)3(#(,/'*"#')'*0(3'"/(*#')I>BA)*(%%")(cLp1&$0%"7'"G)B@)*(%%")K1%&",'"G)B@)*(%%")U$/"*'"J)0(*2")(0#(*0'$*')1%#(,'$,')*(&%')1%#'/')?@)"**'q)L)<$%$)'*)7'%%"&&')$)6'--$%()-'##"3'*(G)0$%$),1,"%')()0$%$)'*)6'"*1,()"%%17'$*"%')3(')#,'C1#",')3(%)V"*1C'$9)L)<$%$)'*)-(,#')-"0(&&'"#'9)L)<$%$)'*3'7'31')-.()7'7$*$)0$##$)%$)0#(00$)#(##$)()/"*&'"*$)%$)0#(00$)-'C$9)

;","##(,'0#'-.()-%'*'-.(Q))_g=`H)!4URHVH)VR)R=;gKSrRH=4G!O(77)(*#(!$+*!%/4+#(!IP!%##)!)#!2(#%!+#5+4)-%8!H)--(!5)!-(4$%*&%!5+//%!4%/%'')%!)#'(*#(!%)!KP<SP!%##)8!!V4;HU<H)R=)^S<RG!!<!R)^S<48! !O)#'(4)!%&$+-)0)-)!w!%#+4)%8!<!RR)^S<48!!_)&01#2)(#+!'161/%*+G!_)0+''(!5)!%-)5)0)-%2)(#+!1*)#%*)%3!)$+*1*)-(&1*)%3!5)0+''(!5)!-(#-+#'*%2)(#+!1*)#%*)%3!$+*5)'%!5)!&%/)3!$*('+)#1*)%!%!6%&&(!$+&(!4(/+-(/%*+8!O+5)4+#'(!1*)#%*)(!#(#!&)7#)0)-%'),(8!L)RRR)^S<48!!E+#'(!+!$*(7*+&&),(!%14+#'(!1*+%!+!-*+%')#)#%8!<!Rj)^S<49! !T*+4)%!'+*4)#%/+!w!%14+#'%'(!*)&-.)(!YI<Q=!RZ!5)!-%*-)#(4%!1*('+/)%/+3!&($*%''1''(!5+/!'*%''(!1*)#%*)(!&1$+*)(*+!4%!%#-.+!5+//%!,+&-)-%8!!_%/!$1#'(!5)!,)&'%!%#%'(4($%'(/(7)-(3!)!*+#)!)#!0%&+!'+*4)#%/+!&)!$*+&+#')!4%*-%'%4+#'+!*)5('')!5)!5)4+#&)(#)3!$('+#5(!4)&1*%*+!I<K!-4!-(4+!5)%4+'*(!4%77)(*+!+!$+&%#5(!%$$+#%!SP!7*%44)8!EB)&'(/(7)%!5)4(&'*%!0)6*(&)!)#'+*&')2)%/+!5)001&%!+!%'*(0)%!'161/%*+3!'*)"00(*2")3')0'&*'+'-"#'7')'*+'%#,"#')'*+'"//"#$,'9)))T#%!4%/%'')%!-(&e!$%*')-(/%*+!#(#!$1N!-.+!5+&'%*+!-1*)(&)'>!-)*-%!/+!&1+!)$('+&)!+2)(/(7)-.+8!a,)5+#'+4+#'+3!5%/!4(4+#'(!-.+!-(/$)&-+!5+'+*4)#%'+!%*++!+!)#5),)51)!-(#,),+#')3!&(#(!,+*(&)4)/)!&)%!)$('+&)!5)!+2)(/(7)%!5%!'(&&)-)!%46)+#'%/)3!&)%!)$('+&)!5)!')$(!7+#+')-(8!L1+&'+!/+!(&&+*,%2)(#)!0%''+!0)#(*%G!!

< O(#(!&'%'+!*)'*(,%'+!'*%--+!5)!&+4)!5)!M*)&'(/(-.)%!-/+4%')&!#+/!$%#+!$*(5(''(!)#!

Page 66: sbobinature nefro_0 - SkyDrive

:1+&'+!2(#+3!$*(6%6)/4+#'+!-(4+!-(#'%4)#%#'+!%46)+#'%/+8!EB%*)&'(/(-.)%!?!1#%!5)!:1+//+!$)%#'+!*+&$(#&%6)/)!5+//%!#+0*($%')%!5)!+*6+!-)#+&)3!-.+!-(/$)&-+!/+!7)(,%#)!5(##+!-.+!0%##(!1&(!5)!$*(5('')!5)4%7*%#')!,+7+'%/)!-)#+&)8!"#!:1+&'(!&+#&(3!/B%*)&'(/(-.)%!$('*+66+!*%$$*+&+#'%*+!1#(!&')4(/(!-*(#)-(!%!6%&&%!)#'+#&)'>8!

< aB!&'%'%!(&&+*,%'%!/%!$*+&+#2%!5)!-(4$/+&&)!0(*4%')!5%!!%-)5(!%*)&'(/(-.)-(!+!_bM!)#!4(/')!5+)!&(77+'')!%00+'')8!

< b+//+!$($(/%2)(#)!%00+''+!5%!#+0*($%')%!+#5+4)-%!5+)!q%/-%#)!&(#(!$*+&+#')!/+!4+5+&)4+!41'%2)(#)!5)!$SK!-%1&%'+!#+)!4(5+//)!&$+*)4+#'%/)!5%//B%-)5(!%*)&'(/(-.)-(8!!

< aB!&'%'(!)$(')22%'(!1#!*1(/(!5+//%!%'&*'#(!D!&1!6%&+!+$)5+4)(/(7)-%!D!4%!%#-(*%!:1+&'%!)$('+&)!#(#!&+46*%!&100)-)+#'+4+#'+!0(*'+8!

< O(#(!&'%')!-.)%4%')!)#!-%1&%!7+#+*)-)!+"##$,')&(*(#'-'9!!!=(+,$6"#'")3")-'-%$06$,'*"))

EB)44+#&(!6+#+0)-)(!-.+!/%!-)-/(&$(*)#%!.%!%$$(*'%'(!%//%!4+5)-)#%!5+)!'*%$)%#')!?!$%*2)%/4+#'+!(&-1*%'(!5%//%!&1%!)4$(*'%#')&&)4%!#+0*('(&&)-)'>8!L1+&'(!?!,+*(!&($*%''1''(!$+*!:1%#'(!*)71%*5%!)/!'*%$)%#'(!5)!*+#+3!+5!?!'%#'(!$)F!)4$(*'%#'+!'+#+*#+!-(#'(!:1%#')!$)F!0%*4%-)!#+0*('(&&)-)!&)!5+-)5%!5)!)4$)+7%*+!#+/!&)#7(/(!$%2)+#'+8!H+*!+&+4$)(3!/B%&&(-)%2)(#+!5)!-)-/(&$(*)#%!+!'%-*(/)41&!,+5+!1#!+00+''(!#+0*('(&&)-(!%55)'),(8!!

M//%!'+*%$)%!-(#!-)-/(&$(*)#%!&)!%&&(-)%#(!5),+*&)!')$)!5)!+,+#'(!%,,+*&(G!

< S1/(*#"#$),'0-.'$)3')(7(*#')-",3'$7"0-$%",'))< R6(,#(*0'$*())< =(+,$#$00'-'#:))< <'*3,$/()(/$%'#'-$L1,(/'-")< S%#(,"2'$*')(%(##,$%'#'-.()I'6(,bG)'6(,O&G)'6$;"J))< S-'3$0')#1C1%",())< V'+(##')-$*-(*#,"2'$*()1,'*",'")

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

NEFROPATIA DA CICLOSPORINA A

Page 67: sbobinature nefro_0 - SkyDrive

)#&100)-)+#2%!*+#%/+!'+*4)#%/+!?!$*%')-%4+#'+!(66/)7%'(8!!\/)#)-%4+#'+3!/%!#+0*($%')%!-*(#)-%!5%!-)-/(&$(*)#%!&)!$*+&+#'%!)#!4(5(!&)4)/+!%5!1#!,'&(##$)-,$*'-$)3'),(*(Q))<!!H*(7*+&&),(!+5!)**+,+*&)6)/+!5+-/)#(!5+//%!01#2)(#+!*+#%/+!-.+!$1N!+,(/,+*+!0)#(!%!aO`_8!!<!\(41#+4+#'+!%&&(-)%'%!%5!)$+*'+#&)(#+!%*'+*)(&%8!!<!b+0*('(&&)-)'>!+&%-+*6%'%!5%!5+$/+2)(#+!&(5)-%8!!M#%'(4)%!$%'(/(7)-%!!"/!:1%5*(!)&'(/(7)-(!?!:1+//(!5)!1#%!0)6*(&)!)#'+*&')2)%/+!@%!&'*)&-+A!+!5)!1#%!-%*%''+*)&')-%!%*'+*)(/($%')%!5+7+#+*%'),%!)%/)#%!5+//B%*'+*)(/%!7/(4+*1/%*+!%00+*+#'+3!-(#&)&'+#'+!)#!*)7(#0)%4+#'(!+#5('+/)%/+3!5+$(&)2)(#+!#(51/%*+!5)!4%'+*)%/+!)%/)#(!$*('+)-(3!%*++!5)!/+&)(#+!+!#+-*(&)!5+//+!-+//1/+!41&-(/%*)!/)&-+!!"/!4(5+//(!$%'(7+#+')-(!$*($(&'(!?!)/!&+71+#'+G!!

!!V+*%$)%!!O(#(!&'%')!0%'')!4(/')!'+#'%'),)!$+*!'*(,%*+!1#%!'+*%$)%!&(55)&0%-+#'+!+!$(&&)6)/4+#'+!)#!7*%5(!5)!0%*!*+7*+5)*+!/%!0)6*(&)!*+#%/+G!-.)%*%4+#'+3!&)!'*%''%!5)!1#!-%4$(!4(/'(!)4$(*'%#'+!$()-.[!&'*+''%4+#'+!-(**+/%'(!%//%!:1%/)'>!5+//%!,)'%!5+)!$%2)+#')!'*%$)%#'%')8!977)!/%!'+*%$)%!&)!0(#5%!+&&+#2)%/4+#'+!&1G!!

< S--1,"#$)/"*#(*'/(*#$)3(%%")-'-%$06$,'*(/'")*(%),"*&()#(,"6(1#'-$)< g#'%'22$)3');;K)3''3,$6','3'*'-')-$/()6,(7(*2'$*()3(%)3"**$),(*"%()< 47'#",()%")3(6%(2'$*()0$3'-")

)"!*)&1/'%')!5)!%/'*)!'+#'%'),)!'+*%$+1')-)!&(#(!*)%&&1#')!)#!:1+&'%!'%6+//%G!

NEFROPATIA DA CICLOSPORINA

PATOGENESI

Bobadilla NA, AJP Renal Physiol 2007; 293: F2

Page 68: sbobinature nefro_0 - SkyDrive

!!!!=(+,$6"#'")3")"-'3$)1,'-$))

))EB%-)5(!1*)-(!?!)/!$*(5(''(!'+*4)#%/+!5+/!-%'%6(/)&4(!5+//+!$1*)#+8!b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l!%-)5(8!d!:1)#5)!+,)5+#'+!-.+3!)#!/)#+%!5)!$*)#-)$)(3!%14+#')!6*1&-.)!5+//B1*)-+4)%3!%#-.+!5)!+#')'>!#(#!+&%7+*%'%3!&(#(!$('+#2)%/4+#'+!)#!7*%5(!5)!5%*+!(*)7)#+!%!$*+-)$)'%2)(#+8!!M/'*)!%#)4%/)!$(&&)+5(#(!1#!-(**+5(!+#2)4%')-(!-.+!$+*4+''+!/(*(!5)!4+'%6(/)22%*+!1/'+*)(*4+#'+!/B%-)5(!1*)-(!%5!%//%#'()#%3!1#%!4(/+-(/%!4(/'(!$)F!)5*(&(/16)/+8!

NEFROPATIA DA CICLOSPORINA

TRATTAMENTO

-  Mantenere i livelli ematici di CyA nel range terapeutico. -  Farmaci che riducono o prevengono la nefrotossicità cronica da

CyA (calcio antagonisti dididropiridinici) -  Evitare deplezione sodica?

Bobadilla NA, AJP Renal Physiol 2007; 293: F2 NEFROPATIA DA ACIDO URICO

ACIDO URICO

PURINE (acidi nucleici)

ALLANTOINA - FILTRAZIONE GLOMERULARE (100 %)

-  RIASSORBIMENTO TCP (90 %) # riassorbimento presecretorio # secrezione # riassorbimento postsecretorio

Ominidi e Primati

superiori Primati inferiori

URICASI

Page 69: sbobinature nefro_0 - SkyDrive

O)'1%2)(#)!)#!-1)!$(&&(#(!,+*)0)-%*&)!%14+#')!5)!1*)-+4)%!&(#(G!< S1/(*#$)3(%%")6,$312'$*()3')"-'3$)1,'-$)

L1+&'(!$1N!,+*)0)-%*&)!&(&'%#2)%/4+#'+!)#!51+!&-+#%*)8!"/!$*)4(3!?!:1+//(!-.+!-(&')'1)&-+!/%!$%'(/(7)%!7+#+')-%!5+//%!7(''%G!%/-1#)!&(77+'')!$(&&)+5(#(!+#2)4)!5+/!4+'%6(/)&4(!$1*)#)-(!$%*')-(/%*4+#'+!%''),)3!+!$*(51-(#(!:1)#5)!1#B+--+&&),%!:1%#')'>!5)!%-)5(!1*)-(8!L1+&'(!$1N!,+*)0)-%*&)!%#-.+!&+!)/!5+0)-)'!+#2)4%')-(!?!%!-%*)-(!5)!1#(!5+7/)!+#2)4)!5+$1'%')!%/!,(-16(,$)!5+//+!6%&)!$1*)#)-.+!Y71%#)#%<)$(g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

!< U'3$##")(0-,(2'$*()

a&)&'(#(!$%'(/(7)+!*+#%/)!-.+3!5%##+77)%#5(!)/!'161/(!$*(&&)4%/+3!$*(,(-%#(!1#!5+0)-)'!5)!&+-*+2)(#+!5)!%-)5(!1*)-(8!H%*)4+#')3!%/-1#)!0%*4%-)!)#)6)&-(#(!)!4+--%#)&4)!&+-*+'(*)!-(4$+'+#5(!-(#!/B%-)5(!1*)-(!$+*!)/!'*%&$(*'%'(*+!5)!%#)(#)!(*7%#)-)!5+//%!4+46*%#%!'161/%*+8!!

!_%/!$1#'(!5)!,)&'%!5+/!-(4$(*'%4+#'(!5+/!*+#+!#+)!-(#0*(#')!5+//B%-)5(!1*)-(3!$(&&)%4(!5)*+!-.+!:1+&'%!4(/+-(/%!0)/'*%!-(4$/+'%4+#'+!%''*%,+*&(!)/!7/(4+*1/(8!M/!/),+//(!5+/!'161/(!$*(&&)4%/+3!&)!,+*)0)-%!1#!$*(-+&&(!5)!*)%&&(*6)4+#'(!$*+<&+-*+'(*)(3!1#(!:1('%!5)!&+-*+2)(#+3!+5!1#%!:1('%!5)!*)%&&(*6)4+#'(!$(&'<&+-*+'(*)(8!"#!'('%/+3!)/!iPR!5)!%-)5(!1*)-(!?!*)%&&(*6)'(8!!!E%!#+0*($%')%!5%!%-)5(!1*)-(!$1N!+&&+*+!5)&')#'%!)#!'*+!')$)!5)!$%'(/(7)%G!!

>9 S-1#")A9 ;,$*'-")D9 =(+,$%'#'"0')

)>9 =(+,$6"#'")"-1#")3")"-'3$)1,'-$)

)L1+&'(!')$(!5)!$%'(/(7)%!&)!&,)/1$$%!)#!&)'1%2)(#)!5)!)$+*$*(512)(#+!%-1'%!5)!%-)5(!1*)-(3!+!-(#&+71+#'+!)$+*1*)-+4)%!+&'*+4%G!&)!$*+&+#'%!-(4+!1#%!+$,/"),"6'3"/(*#()6,$&,(00'7")3')'*01++'-'(*2"),(*"%(9)E+!&)'1%2)(#)!%!*)&-.)(!5)!#+0*($%')%!%-1'%!5)!%-)5(!1*)-(!&(#(!+&&+#2)%/4+#'+G!!

< <'*3,$/()3")%'0')#1/$,"%(!)#!$%2)+#')!(#-(+4%'(/(7)-)!:1%#5(!,)+#+!)#)2)%'%!/%!-.+4)('+*%$)%8!

< =($6%"0'()$*-$(/"#$%$&'-.(3!!%#-.+!)#5)$+#5+#'+4+#'+!5%//%!-.+4)('+*%$)%3!$+*-.[!)/!*%'+!$*(/)0+*%'),(!$%*')-(/%*4+#'+!+/+,%'(!5+'+*4)#%!1#%!$*(512)(#+!+#(*4+!5)!%-)5(!1*)-(8!!!

"/!:1%5*(!$*+,+5+!/%!5+$(&)2)(#+!5)!-*)&'%//)!5)!%-)5(!1*)-(!#+)!'161/)3!#+)!5('')!-(//+''+*)3!#+//%!$+/,)!+!#+7/)!1*+'+*)C!&$+&&(!/+!/+&)(#)!&(#(!6)/%'+*%/)3!+!-(&e!&)!&,)/1$$%!1#!:1%5*(!5)!)#&100)-)+#2%!*+#%/+!%-1'%3!-(#!(/)71*)%!+!*%$)5(!*)%/2(!5+//%!-*+%')#)#+4)%8!T#!,"66$,#$)1,'-$01,'"E-,("#'*'*1,'")/"&&'$,()3')>)$+*4+''+!5)!5)&)'#71+*+!:1+&'%!-(#5)2)(#+!5%!%/'*+!-(#5)2)(#)!-.+!$(&&(#(!-%1&%*+!)#&100)-)+#2%!*+#%/+!%-1'%8!E%!#+0*($%')%!%-1'%!5%!%-)5(!1*)-(!&)!%,,%/+!&($*%''1''(!5)!&'*%'+7)+!$*+,+#'),+!#+)!$%2)+#')!%!*)&-.)(8!"#!7+#+*+3!&)!&(44)#)&'*%!"%%$61,'*$%$)YIPP<JPP!47U5)+Z)!&)!

Page 70: sbobinature nefro_0 - SkyDrive

"%-"%'*'22"*$)%()1,'*()")6h)6",')")f)$)016(,'$,(!-(#!6)-%*6(#%'(!(!"-(#"2$%"/'3(9)M#-.+!/B1&(!5)!$('+#')!5)1*+')-)!Y+&G!01*(&+4)5+3!4%##)'(/(Z!$+*4+''+!5)!%66%&&%*+!+00)-%-+4+#'+!/%!-(#-+#'*%2)(#+!5)!%-)5(!1*)-(!#+/!0)/'*%'(8!!!

A9 =(+,$6"#'")-,$*'-")'6(,1,'-(/'-")I&$##$0"J))_%!'+4$(!?!#('(!-.+!/B)$+*1*)-+4)%!-*(#)-%!?!-%1&%!5)!)#&100)-)+#2%!*+#%/+!#+/!/1#7(!$+*)(5(8!V*%5)2)(#%/4+#'+3!/(!&-.+4%!$%'(7+#+')-(!,+#),%!-(&e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`%$/(,1%$0-%(,$0'9))V1''%,)%3!(&&+*,%2)(#)!$)F!*+-+#')!.%##(!$%*2)%/4+#'+!4+&&(!)#!5)&-1&&)(#+!:1+&'(!&-.+4%!-/%&&)-(G!!!

< Lo sviluppo di nefropatia gottosa non è comune nella stragrande maggioranza di pz con gotta.

< Le lesioni istologiche più frequenti documentabili in pz iperuricemici con

insufficienza renale sono a carico dei vasi (nefrosclerosi).

< È improbabile che iperuricemia e gotta da sole conducano a significativa

insufficienza renale.

< Studi epidemiologici non sono riusciti ad identificare l’acido urico come fattore di

rischio indipendente di insufficienza renale.

< Lo sviluppo di insufficienza renale in pazienti iperuricemici (asintomatici e gottosi) è usualmente attribuibile all’associata ipertensione arteriosa.

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

Page 71: sbobinature nefro_0 - SkyDrive

&$)+7%*+!)/!/+7%4+!'*%!)$+*1*)-+4)%!-*(#)-%!+!#+0*($%')%8!!

!!V+*%$)%!!EB1')/)'>!5+//%!'+*%$)%!)$(1*)-+4)22%#'+!?!4(/'(!5)6%''1'%3!'%#'(!$)F!-.+!/B%//($1*)#(/(!?!)#!7*%5(!5)!-%1&%*+!*+%2)(#)!%#%0)/%'')-.!$('+#2)%/4+#'+!0%'%/)!)#!1#%!$+*-+#'1%/+!#(#!)#&)7#)0)-%#'+!5)!$%2)+#')8!"#!7+#+*%/+3!/%!#(,"6'")-$*)"%%$61,'*$%$)i),"--$/"*3"#")0$%$)'*)6"2'(*#')-$*)'6(,1,'-(/'")0'*#$/"#'-"8!E%!-%/-(/(&)!1*%')-%!+!/+!4%#)0+&'%2)(#)!7(''(&+!*)&$(#5(#(!6+#+!%//B%//($1*)#(/(!Y+5!+,+#'1%/4+#'+!%#-.+!%//%!-(/-.)-)#%Z3!4%!*$*)-5i)(7'3(*2")3(%)+"##$)-.()%")#(,"6'")/'&%'$,')%")+1*2'$*(),(*"%()$)*(),"%%(*#')'%)3(-"3'/(*#$9)h)!&(#(!)#,+-+!5%')!-.+!&(&'+#7(#(!/B1')/)'>!5)!5)1*+')-)!+!M\a<"!#+/!-(#'*(//(!5+//B)$+*'+#&)(#+!+!:1)#5)!5+/!5%##(!*+#%/+8!!b+)!$%2)+#')!-(#!)$+*1*)-+4)%!%&)#'(4%')-%!/%!'+*%$)%!#(#!?!*%--(4%#5%'%8!!!!=(+,$6"#'")'6(,-"%-(/'-"))EB)$+*-%/-+4)+!$1N!$(*'%*+!%!5),+*&+!-(#&+71+#2+!%!/),+//(!*+#%/+!%!&+-(#5%!-.+!&)!'*%'')!5)!1#%!-(#5)2)(#+!%-1'%!(!5)!1#%!-(#5)2)(#+!-*(#)-%8!"#!-%&(!5)!)$+*-%/-+4)%!%-1'%3!/+!4%#)0+&'%2)(#)!*+#%/)!&(#(!,(7(,0'C'%'G!$*)#-)$%/4+#'+3!&)!'*%''%!5)!1#%!-(#5)2)(#+!5)!7"0$-$0#,'2'$*()-(#!,'312'$*()3(%)+%100$)6%"0/"#'-$),(*"%(!+!-(#&+#71+#'+!*)512)(#+!*+,+*&)6)/+!5+/!`^U9)))_),+*&(!)/!5)&-(*&(!$+*!/B'6(,-"%-(/'")-,$*'-"9)\%1&+!*+/%'),%4+#'+!-(41#)!5)!)$+*-%/-+4)%!-*(#)-%!&(#(G!!

< R6(,6","#',$'3'0/$)< <",-$'3$0')

INSUFFICIENZA RENALE

IPERURICEMIA CRONICA

AUMENTATO INGRESSO DI ACIDO URICO IN CELLULE ENDOTELIALI, MM LISCE VASCOLARI

DISFUNZIONE ENDOT. RILASCIO NO

ATTIVAZIONE SISTEMA RENINA-ANGIOTENSINA

ROS ED ALTRI MEDIATORI

INFIAMMATORI

PROLIFERAZIONE CELLULE MM

LISCE VASCOLARI

VASOCOSTRIZIONE (SISTEMICA E RENALE)

IPERTENSIONE (insensibile al sale)

ARTERIOLOPATIA AFFERENTE FIBROSI INTERSTIZIALE

IPERTENSIONE (sensibile al sale)

Page 72: sbobinature nefro_0 - SkyDrive

< O'(%$/")/1%#'6%$)< O(#"0#"0')$0#($%'#'-.()< R*#$00'-"2'$*()3")7'#"/'*")V)

)

))L1)#5)3!,)!&(#(!51+!%&$+'')!)#!:1+&'(!')$(!5)!$%'(/(7)%G!!

W8 j"0$-$0#,'2'$*(),(*"%()()0'0#(/'-"G!\%1&%'%!5%//B)$+*-%/-+4)%!-*(#)-%3!5+'+*4)#%!)&-.+4)%!-*(#)-%!)#!$*+,%/+#2%!%!-%*)-(!5+//%!4)5(//%*+!*+#%/+3!+!:1)#5)!5+)!'161/)!*+#%/)8!

I8 )V(6$0'2'$*()3')0"%')3')-"%-'$)I*(+,$-"%-'*$0'JG!)/!-%/-)(3!*%77)1#7+#5(!+/+,%'+!-(#-+#'*%2)(#)!1*)#%*)+3!'+#5+!%!$*+-)$)'%*+3!-%1&%#5(!/%!0(*4%2)(#+!5)!-*)&'%//)8!!L1+&'(!+,+#'(!5+'+*4)#%!%'*(0)%!'161/%*+3!&)%!$+*!/B+00+''(!(&'*1''),(3!&)%!$+*-.[!)!-*)&'%//)!5+'+*4)#%#(!$*(-+&&)!0/(7)&')-)!5%!-(*$)!+&'*%#+)8!!

!E%!-%'*'-")$*+,+5+G!!

< R6(,-"%-(/'"E'6(,-"%-'1,'")< R6$0#(*1,'")Y$+*!%/'+*%2)(#+!5+//%!4)5(//%*+!+!5+)!'161/)Z)< =(+,$-"%-'*$0')/"-,$0-$6'-")< R*01++'-'(*2"),(*"%()-,$*'-")Y*%*%Z)< 47(*#1"%/(*#(Q)7/)-(&1*)%3!%4)#(%-)51*)%3!$*('+)#1*)%!'161/%*+3!%-)5(&)!'161/%*+3!

%/-%/(&)!4+'%6(/)-%3!)$+*4%7#+&1*)%8!))E%!*(+,$-"%-'*$0'!?!1#%!-(#5)2)(#+!-%*%''+*)22%'%!5%!5)001&%!+!0)#+!-%/-)0)-%2)(#+!5+/!$%*+#-.)4%!*+#%/+!*%5)(/(7)-%4+#'+!5)4(&'*%6)/+3!5),+*&%!5%!:1+//%!-.+!&)!5)4(&'*%!)4$+7#%*+!)!-(//+''(')3!/+!,)+!+&-*+'*)-)!+!/%!,+&-)-%!Y!!*(+,$%'#'"0'Z8!!

NEFROPATIA CRONICA IPERCALCEMICA

IPERCALCEMIA CRONICA

CONCENTRAZIONE INTRATUBULARE DI CALCIO

(midollare)

VASOCOSTRIZIONE (sistemica e renale)

filtrazione glomerulare

DEPOSIZIONE INTERSTIZIALE DI CALCIO

OSTRUZIONE INTRATUBULARE

INFILTRAZIONE CELLULARE MONONUCLEATA

DEGENERAZIONE/NECROSI CELLULE TUBULARI (midollare)

ISCHEMIA/IPOSSIA (preval. midollare)

Page 73: sbobinature nefro_0 - SkyDrive

!!`%*%4+#'+!/%!#+0*(-%/-)#(&)!)#'+*+&&%!/%!-$,#'-"%(3!+!7+#+*%/4+#'+!&)!'*%''%!5)!-%&)!&+-(#5%*)!%!#+-*(&)!-(*')-%/+!%-1'%8!E%!/'3$%%",()?!/B%*+%!$)F!)#'+*+&&%'%!+!)/!0%''(*+!5)!*)&-.)(!$*)#-)$%/+!?!*%$$*+&+#'%'(!5%//B)$+*-%/-)1*)%8!E+!-(#5)2)(#)!)#!-1)!&)!$1N!&,)/1$$%*+!#+0*(-%/-)#(&)!4)5(//%*+!&(#(G!!

!!!!!!!!!!!!!

TUBULI CONTENENTI CRISTALLI CON

EPITELIO NORMALE

TUBULI CON CRISTALLI ADERENTI A CELLULE

RIGENERANTI APPIATTITE

TUBULI CON CRISTALLI SORMONTATI DA

EPITELIO TUBULARE

TUBULI CON CRISTALLI “DIREZIONATI”

NELL’INTERSTIZIO

GRANULOMA

NASCITA DELLA NEFROCALCINOSI (microscopica)

Vervaet BA, Kid Int 2009; 75: 41 NEFROCALCINOSI MIDOLLARE

-  Iperparatiroidismo primitivo (1ª causa) -  Acidosi tubulare distale (2ª causa) -  Rene a spugna midollare (depositi in dotti collettori terminali dilatati) -  Necrosi papillare -  TBC renale -  Immobilizzazione prolungata (specialmente in età pediatrica) -  Senilità, menopausa, steroidi -  Sindrome da latte ed alcali -  Ipervitaminosi D -  Rachitismi vit D resistenti (trattati con vit D) -  Sarcoidosi -  Iperossaluria primitiva -  Prematurità

CAUSE

Page 74: sbobinature nefro_0 - SkyDrive

=(+,$6"#'()#1C1%$'*#(,0#'2'"%')'//1*$/(3'"#())_),+*&+!$%'(/(7)+!5)!-%*%''+*+!%1'()441#+!D!(!-(41#:1+!)441#(4+5)%'(!D!$(&&(#(!%--(4$%7#%*&)!%!5%##(!*+#%/+!'161/()#'+*&')2)%/+8!H*+#5+*+4(!)#!-(#&)5+*%2)(#+!/%!&)#5*(4+!5)!Opy7*+#3!/%!#+0*)'+!)#'+&')2)%/+!%//+*7)-%!+!/%!&%*-()5(&)3!4%!&%*+66+*(!4(/'+!/+!4%/%'')+!5%!'*%''%*+!D!$+*!+&+4$)(3!)/!-()#,(/7)4+#'(!*+#%/+!)#!-(*&(!5)!&-/+*(&)!&)&'+4)-%3!1#%!5+//+!$*)#-)$%/)!-%1&+!5)!4(*'+!$+*!:1+&')!$%2)+#')8!!!

>9 <'*3,$/()3')<\m&,(*)!

"/!-()#,(/7)4+#'(!*+#%/+!#+//%!&)#5*(4+!5)!Opy7*+#!?!)#!*+%/'>!%66%&'%#2%!0*+:1+#'+8!O)!*)')+#+!-.+!)#'+*+&&)!-)*-%!1#!'+*2(!5+)!$%2)+#')8!X(/'+!&(#(!/+!0(*4+!5)!$%'(/(7)%!*+#%/+!+,)5+#2)%6)/)!)#!-(*&(!5)!Opy7*+#G!!`%$/(,1%$*(+,'#'Q))

< O(/C,"*$0"))< O(0"*&'"%()< O(/C,"*$6,$%'+(,"#'7")

E+!7/(4+*1/(#+0*)')!&(#(!%66%&'%#2%!*%*+!+!&)!*)&-(#'*%#(!&($*%''1''(!#+)!-%&)!)#!-1)!/%!4%/%'')%!?!%&&(-)%'%!%!-*)(7/(61/)#+4)%!(!EaO8!!=(+,'#()'*#(,0#'2'"%())E%!*(+,'#()'*#(,0#'2'"%(!)#!-(*&(!5)!&)#5*(4+!5)!Opy7*+#!$1N!%#-.+!+&&+*+!1#%!4%#)0+&'%2)(#+!$*+-(-+3!$*+-+5+#5(!5)!Q<S!%##)!/%!&)#5*(4+!&+--%8!\/)#)-%4+#'+3!&)!$*+&+#'%!-(#G!!

< R6$0#(*1,'")< U'312'$*()3(%%")-%(","*-()3(%%")-,("#'*'*")< R6$W"%'(/'"!$%*')-(/%*4+#'+!&$)--%'%)< S-'3$)#1C1%",()3'0#"%()-$/6%(#")

V1''(!:1+&'(!%&&14+!)!-(#'(*#)!5)!1#%!)#&100)-)+#2%!*+#%/+!5)!7*%5(!4(5+&'(3!-1)!&)!%&&(-)%#(!/+!4%#)0+&'%2)(#)!5)!5)&01#2)(#+!'161/%*+!$*(&&)4%/+!+U(!5)&'%/+8!E%!5)&01#2)(#+!'161/%*+!5)&'%/+!-%1&%!%-)5(&)!'161/%*+!5)&'%/+3!#+0*(-%/-)#(&)!+!)$(&'+#1*)%8!E%!5)&01#2)(#+!'161/%*+!$*(&&)4%/+!$1N!$*+&+#'%*&)!-(#!)/!:1%5*(!5+//%!&)#5*(4+!5)!k%#-(#)!(!-(#!,%*)+!-(46)#%2)(#)!5+//+!&1+!-(4$(#+#')8!EB)$(]%/)+4)%!$1N!+&&+*+!$%*')-(/%*4+#'+!4%*-%'%!+!$1N!-%1&%*+!%**+&'(!-%*5)%-(!%&)&'(/)-(8!!E%!'+*%$)%!&)!0%!)#!7+#+*+!-(#!&'+*()5)!+5!)441#(&($$*+&&(*)3!4%!/%!&1%!+00)-%-)%!?!4(/'(!-(#'*(,+*&%8!!!!

A9 =(+,$6"#'")'*#(,0#'2'"%()"%%(,&'-"))L1+&'(!')$(!5)!$%'(/(7)%!&)!-(#0)71*%!-(4+!1#%!*+%2)(#+!)441#(4+5)%'%!-%1&%'%!5%//B%&&1#2)(#+!5)!%/-1#)!0%*4%-)3!-(#!-(#&+71+#'+!#+0*($%')%!'161/()#'+*&')2)%/+!%-1'%!5)001&%8!^/)!%7+#')!#('(*)%4+#'+!%&&(-)%')!&(#(G!!

< O1/0%4)5)-)!< H+#)-)//)#+!< \+0%/(&$(*)#+!< \)$*(0/(g%-)#%!+!#(*0/(g%-)#%!< "&(#)%2)5+!< `)0%4$%-)#%!

Page 75: sbobinature nefro_0 - SkyDrive

< X+&%/%2)#%!< M#')<lI!< _)1*+')-)!5+//B%#&%!

!V%/,(/'%!)/!:1%5*(!&)!$*+&+#'%!-(#!)#&100)-)+#2%!*+#%/+3!0+66*+3!+(&)#(0)/)%!+5!+*)'+4%!-1'%#+(!D!+!)#!:1+&'(!-%&(!/%!5)%7#(&)!?!4(/'(!&+4$/)-+8!H1*'*($$(!$+*N3!)/!:1%5*(!')$)-(!?!&$+&&(!%&&+#'+8!^+#+*%/4+#'+3!-(41#:1+3!)/!5%##(!*+#%/+!?!-(4$/+'%4+#'+!*+,+*&)6)/+!-(#!/%!&(&$+#&)(#+!5+/!0%*4%-(8!!!"#!-%&(!5)!7/(4+*1/(#+0*)'+!/1$)-%3!$()3!?!0*+:1+#'+!)/!-()#,(/7)4+#'(!5+)!'161/)!+!5+//B)#'+*&')2)(8!L1+&'(!$1N!5)$+#5+*+!5%!4(/')!0%''(*)G!!

< _+$(&)2)(#+!5)!)441#(-(4$/+&&)!%#-.+!#+//+!4+46*%#+!6%&%/)!'161/%*)!< k)/'*%2)(#+!%''*%,+*&(!/%!4+46*%#%!7/(4+*1/%*+!#(#!$)F!)#'+7*%!5)!$*('+)#+!

'(&&)-.+!$+*!)!'161/)!< H*(512)(#+!5)!-)'(-.)#+!-.+!*%77)1#7(#(!/+!-+//1/+!'161/%*)!-%1&%#5(#+!%/'+*%2)(#)!

)#0)%44%'(*)%!< `)512)(#+!5+/!0/1&&(!+4%')-(!$+*)'161/%*+!&+-(#5%*)(!%//%!*)512)(#+!5+//%!

$+*01&)(#+!5+)!7/(4+*1/)!-(**)&$(#5+#')3!+!:1)#5)!)&-.+4)%!5+)!'161/)!!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

!

Page 76: sbobinature nefro_0 - SkyDrive

b+0*($%')+!h%&-(/%*)!

E+!#+0*($%')+!,%&-(/%*)!&(#(!1#!7*1$$(!5)!$%'(/(7)+!5)!7*%#5+!)4$(*'%#2%8!H(&&(#(!+&&+*+!-/%&&)0)-%'+!%#2)'1''(!&1//%!6%&+!5+/!5)&'*+''(!,%&-(/%*+!-()#,(/'(G!",#(,'"),(*"%()6,'*-'6"%()()01$'),",'G)",#(,'$%(),(*"%')(!7(*"),(*"%(9)O1!:1+&'%!6%&+3!$(&&)%4(!)#:1%5*%*+!/+!,%*)+!$%'(/(7)+!#+0*(,%&-(/%*)G!

>9 S,#(,'"),(*"%()()01$'),"/'))

< H--%10'$*()I8,$/C$0'G)4/C$%'"J)< <#(*$0'))

X(#(/%'+*%/+!q)/%'+*%/+!(!)#!4(#(*+#+!

!

A9 S,#(,'$%(),(*"%')< R6(,#(*0'$*()C(*'&*")$)/"%'&*")< !,(L(-%"/60'")E)(-%"/60'")< O"%"##'")"#(,$(/C$%'-")< j"0-1%'#')0'0#(/'-.()< <'*3,$/()1,(/'-$L(/$%'#'-")< !$,6$,")#,$/C$#'-")#,$/C$-'#$6(*'-")< =(+,$6"#'")'*)-$,0$)3')0-%(,$3(,/'")< =(+,$6"#'")'*)-$,0$)3')"*(/'")+"%-'+$,/()

)

D9 j(*"),(*"%())

< 8,$/C$0')3(%%")7(*"),(*"%()$)3(%%()7(*()0(&/(*#",'()

)

=(+,$6"#'()3")"%#(,"2'$*')3(%%()",#(,'(),(*"%')6,'*-'6"%')

\(4+!&)!?!5+''(3!/+!%*'+*)+!*+#%/)!$*)#-)$%/)!+5!)!/(*(!*%4)!$(&&(#(!%#5%*+!)#-(#'*(!0(#5%4+#'%/4+#'+!%!51+!$*(-+&&)!$%'(/(7)-)G!/%!&'+#(&)!+!/B(--/1&)(#+8!"#)2)+*+4(!(--1$%#5(-)!5+//B$--%10'$*(9)EB(--/1&)(#+!5+//B%*'+*)%!*+#%/+!$*)#-)$%/+!+!5+)!&1()!*%4)!$1N!+&&+*+!5(,1'%!&(&'%#2)%/4+#'+!%!51+!')$)!5)!%/'+*%2)(#)!$%'(/(7)-.+G!/%!#,$/C$0')+!/B(/C$%'"9)h+5)%4(!%//(*%!:1%/)!$(&&(#(!+&&+*#+!/+!-%1&+8!

;"10()3')#,$/C$0')3(%5",#(,'"),(*"%(Q)

< S#(,$0-%(,$0')< j"0-1%'#'))< V'00(2'$*()"$,#'-")$)3(%%5",#(,'"),(*"%()< S*(1,'0/")"$,#'-$)$)3(%%5",#(,'"),(*"%()< V'06%"0'")+'C,$/10-$%",()< 8,"1/"))< S*&'$&,"+'")

)

)

)

Page 77: sbobinature nefro_0 - SkyDrive

;"10()3')(/C$%'")3(%%5",#(,'"),(*"%(Q)

)

< ^'C,'%%"2'$*()"#,'"%()< <#(*$0')/'#,"%'-")< 4/C$%'")3")(*3$-",3'#()< 8,$/C$0')/1,"%()'*#,"-",3'"-")< !,$#(0')7"%7$%",()< O'c$/")"#,'"%()< 4/C$%'")*($6%"0#'-")< 4/C$%'")6","3$00")

EB(--/1&)(#+!5+//B%*'+*)%!*+#%/+!?!4(/'(!&$+&&(!1#!$*(-+&&(!+46(/)-(!Y5%!0)6*)//%2)(#+!%'*)%/+Z3!$)F!*%*%4+#'+!&)!'*%''%!)#,+-+!5)!1#!0+#(4+#(!&1!6%&+!'*(46(')-%8!H+*!5+0)#)2)(#+3!:1%#5(!&)!,+*)0)-%!1#B(--/1&)(#+!5+//B%*'+*)%!*+#%/+3!)/!0/1&&(!&%#71)7#(!5)*+''(!%/!*+#+!*)&1/'%!-(4$/+'%4+#'+!)#'+**(''(8!E+!-(#&+71+#2+!&(#(!5)!7*%,)'>!,%*)%6)/+!%!&+-(#5%!5)G!

< h+/(-)'>!-(#!-1)!&)!)#&'%1*%!/B+,+#'(!< M*'+*)%!)#'+*+&&%'%!+!-(**)&$(#5+#'+!'+**)'(*)(!)**(*%'(!< a#')'>!5+/!-)*-(/(!-(//%'+*%/+!

"/!:1%5*(!$)F!7*%,+!?!:1+//(!5+//B'*+",#$),(*"%()"-1#$3!/%!-1)!+&'+#&)(#+!5)$+#5+*>!(,,)%4+#'+!5%!:1%/+!%*'+*)%!&)!'*(,)!%5!+&&+*+!(--/1&%8!b+/!SPR!5+)!-%&)!:1+&'(!0+#(4+#(!?!&)#'(4%')-(G!)/!$%2)+#'+!$*+&+#'%!5(/(*+!/(46%*+3!#%1&+%3!,(4)'(3!0+66*)-(/%3!/+1-(-)'(&)3!"1/(*#$)3(%%5"2$#(/'")+!5+//%!-,("#'*'*(/'"3!%14+#'(!5+7/)!+#2)4)!&)+*)-)!YE_l3!MEV3!0(&0%'%&)!%/-%/)#%Z!+!#+//+!1*)#+!YE_l3!0(&0%'%&)!%/-%/)#%Z8!"/!0(3'/(*#$!?!%/'+*%'(G!%66)%4(!)#0%'')!$*('+)#1*)%!+!4)-*(+4%'1*)%8!EB%*+%!)&-.+4)-%!/)6+*%!1#%!7*%#5+!:1%#')'>!5)!*+#)#%3!-(&)--.[!&)!%,*>!%#-.+!'6(,#(*0'$*()",#(,'$0"!-(#!+/+,%'%!H`M8!EB+#')'>!5+//%!*)512)(#+!5+//%!01#2)(#+!*+#%/+!5)$+#5+!5%//B+&'+#&)(#+!5+//B%*+%!)#0%*'1%'%8!L1)#5)3!*)-%$)'(/%#5(G!

< U'312'$*()7",'"C'%()3(%)+'%#,"#$)&%$/(,1%",()< R6(,"2$#(/'"G)'6(,-,("#'*'*(/'")< R6(,#(*0'$*()-$*)(%(7"#")!US)< S1/(*#$)3(&%')(*2'/')0'(,'-')IS_8G)S_!G)_VhJ)< S1/(*#$)3(&%')(*2'/')1,'*",')I_VhG)S_!J)< S%#(,"2'$*')3(%)0(3'/(*#$)I6,$#('*1,'"G)/'-,$(/"#1,'"J)< _(1-$-'#$0')< R*$%#,(G)0+66*+3!5(/(*+3!#%1&+%!+!,(4)'(!#+/!SPR!5+)!-%&)8)

_")3'"&*$0')?!%7+,(/+!#+//+!0(*4+!&)#'(4%')-.+!+!&)!6%&%!&1//B1&(!5+//Ba-(<_($$/+*3!4%!%#-.+!V\!+5!`Xb!&'%##(!%&&14+#5(!1#!*1(/(!5)!$*)4(!$)%#(!#+//B)4%7)#7!5+//B%*'+*)%!*+#%/+8!!

E%!#(,"6'"!?!4+5)-%!(!-.)*1*7)-%3!%!&+-(#5%!5+//+!#+-+&&)'>8!E%!'+*%$)%!4+5)-%!&)!0(#5%!&1//B)4$)+7(!5)!%#')-(%71/%#')3!'*(46(/)')-)3!)$('+#&),%#')!+!4)&1*+!5)!&1$$(*'(3!-.+!$(&&(#(!)#-/15+*+!%#-.+!/%!5)%/)&)8!"#!-%&(!5)!(--/1&)(#+!&+-(#5%*)%!%5!+46(/)%!5%!0)6*)//%2)(#+!%'*)%/+3!?!($$(*'1#(!'+#'%*+!5)!*)$*)&')#%*+!)/!*)'4(!&)#1&%/+!+!-(41#:1+!/%!'+*%$)%!%#')-(%71/%#'+!?!%&&(/1'%4+#'+!)#5)&$+#&%6)/+8!b+//+!0(*4+!-(#!&,"7()-$/6,$/'00'$*()+1*2'$*"%(!Y&$+-)%/4+#'+!$(&'<'*%14%')-.+Z!?!&$+&&(!)#5)-%'(!/B%$$*(--)(!-.)*1*7)-(3!-.+!-(#&)&'+!#+//%!*),%&-(/%*)22%2)(#+8!!

!

Page 78: sbobinature nefro_0 - SkyDrive

<#(*$0')3(%%5",#(,'"),(*"%()

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b(#!?!5)00)-)/+!-%$)*+!)/!/+7%4+!'*%!&'+#(&)!5+//B%*'+*)%!*+#%/+!+!)$+*'+#&)(#+8!T#!$*(-+&&(!-.+!5+'+*4)#)!&'+#(&)!5+//B%*'+*)%!*+#%/+!(/'*+!1#%!&(7/)%!-*)')-%!Ys=PRZ3!5+'+*4)#%!(,,)%4+#'+!1#%!*)512)(#+!5+/!0/1&&(!$/%&4%')-(!*+#%/+8!b(*4%/4+#'+3!)/!0++56%-]!'161/(<7/(4+*1/%*+!?!)#!7*%5(!5)!4(51/%*+!)/!'(#(!5+//+!%*'+*)(/+!%00+*+#')!$+*!0%*!&e!-.+3!%!0*(#'+!5)!,%*)%2)(#)!5+/!kH`!+!5+//%!$*+&&)(#+!5)!$+*01&)(#+3!)/!^k`!&)!4%#'+#7%!*+/%'),%4+#'+!-(&'%#'+C!)#!:1+&'(!-%&(3!$+*N3!&)%4(!6+#!(/'*+!/+!-%$%-)'>!5)!-(4$+#&(8!M--%5+3!%//(*%3!-.+!)/!0)/'*%'(!7/(4+*1/%*+!'+#5%!%!*)51*&)3!)#!:1%#'(!-(#!/B%$$(*'(!+4%')-(!*)5(''(!*)&1/'%!+&&+*+!*)5(''%!%#-.+!/%!$*+&&)(#+!)5*(&'%')-%!7/(4+*1/%*+8!E%!*)512)(#+!5+/!0)/'*%'(!7/(4+*1/%*+!5+'+*4)#%!/%!*)512)(#+!5+/!-%*)-(!5)!b%\/!)#!%**),(!%//%!4%-1/%!5+#&%3!+!:1)#5)!/B%''),%2)(#+!D!'*%4)'+!-(4$/+&&)!&+7#%/)!4+5)%')!%#-.+!5%/!4+&%#7)(!+g'*%7/(4+*1/%*+!D!5+)!&)&'+4)!'+&)!%/!4%#'+#)4+#'(!5+//B(4+(&'%&)G!

< O)&'+4%!*+#)#%<%47)('+#&)#%<%/5(&'+*(#+!< O)&'+4%!#+*,(&(!&)4$%')-(!

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h\a3!+!:1)#5)!&)!%''),%!/(!&'+&&(!4+--%#)&4(!-.+!&)!%''),+*+66+!)#!-(*&(!5)!5+$/+2)(#+!,(/+4)-%3!*)&1/'%#5(#+!1#%!*)&$(&'%!+00)-%-+!%!/"%"3"##"#'7"9))

EB+2)(/(7)%!5+//%!&'+#(&)!5+//B%*'+*)%!*+#%/+!$1N!+&&+*+!*)%&&1#'%!)#!51+!$*)#-)$%/)!$%'(/(7)+G!

< S#(,$0-%(,$0')

EB%'+*(&-/+*(&)!*+#5+!-(#'(!5+/!i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

!

Page 79: sbobinature nefro_0 - SkyDrive

< V'06%"0'")+'C,$/10-$%",()

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d!4(/'(!*%*(!-.+!/%!5)&$/%&)%!0)6*(41&-(/%*+!&)%!-%1&%!5)!(--/1&)(#+!'('%/+!5+//B%*'+*)%!*+#%/+3!+!)#!:1+&'(!-%&(!)#'+*,+#7(#(!$+*!/(!$)F!0+#(4+#)!'*(46(')-)8!

!

E%!5)&$/%&)%!0)6*(41&-(/%*+3!$1*!+&&+#5(!5)!7*%#!/1#7%!$)F!0*+:1+#'+!%/!/),+//(!5+//B%*'+*)%!*+#%/+3!?!1#%!$%'(/(7)%!5%)!-%*%''+*)!&)&'+4)-)!-.+!$1N!)#'+*+&&%*+!%#-.+!%/'*)!5)&'*+'')3!$*)4(!'*%!'1'')!:1+//(!-+*+6*(,%&-(/%*+G!&(#(!&$+&&(!)#'+*+&&%')!)!*%4)!+g'*%-*%#)-)!5+//%!-%*(')5+!(!/B%*'+*)%!,+*'+6*%/+8!V1''%,)%3!4(/')&&)4)!&(#(!)!5)&'*+'')!-.+!$(&&(#(!+&&+*+!)#'+*+&&%')3!-(4$*+&%!/%!-)*-(/%2)(#+!%*'+*)(&%!5+7/)!%*')8!!

!

!

!

10

Page 80: sbobinature nefro_0 - SkyDrive

^'0'$6"#$%$&'")3(%%")0#(*$0')3(%%5",#(,'"),(*"%()

)

)

L1%#5(!&)!)#&'%1*%!1#%!&'+#(&)!4(#(/%'+*%/+3!#+/!*+#+!)#'+*+&&%'(!.%##(!)#)2)(!)!$*(-+&&)!5)!-1)!$%*/%,%4(!$(-(!0%8!E%!*)512)(#+!5+//%!$+*01&)(#+!+!5+/!^k`!5+'+*4)#%!/B%''),%2)(#+!5+/!&)&'+4%!*+#)#%<%#7)('+#&)#%!Y`MOZ3!)/!:1%/+!*)$(*'%!)/!^k`!%!,%/(*)!#(*4%/)!%/!$*+22(!5)!-%1&%*+!1#B)$+*'+#&)(#+!%#7)('+#&)#%!""!5)$+#5+#'+8!M/!/),+//(!5+/!*+#+!&%#(3!5(,+!#(#!+&)&'+!&'+#(&)3!/B%14+#'(!5+//%!$*+&&)(#+!%*'+*)(&%!&)&'+4)-%!&)!'*%51-+!)#!1#B%14+#'%'%!$*+&&)(#+!7/(4+*1/%*+G!7*%2)+!%/!+((3C"-W)#1C1%$L&%$/(,1%",(3!&)!%,*>!%//(*%!/%!&($$*+&&)(#+!5+/!`MO!%/!/),+//(!5+/!/%'(!&%#(!+!1#%!6,(001,()*"#,'1,(0'03!-)(?!1#!%14+#'(!5+//B+&-*+2)(#+!5)!&(5)(!5%!$%*'+!5+/!*+#+!&%#(!-(4+!4+--%#)&4(!-(4$+#&%'(*)(!5+//B)$+*'+#&)(#+8!O+!#()!%#5)%4(!%!6/(--%*+!)/!`MO!0%*4%-(/(7)-%4+#'+3!#(#!(&&+*,+*+4(!#+&&1#!+00+''(!&1//%!01#2)(#+!5+/!*+#+!&%#(3!4%!(&&+*,+*+4(!)#,+-+!1#%!*)512)(#+!%-1'%!5+/!0)/'*%'(!7/(4+*1/%*+!5+/!*+#+!-(#!%*'+*)%!&'+#(')-%3!)#!-1)!)/!4%#'+#)4+#'(!5+/!^k`!?!'('%/4+#'+!5)$+#5+#'+!5%/!`MO8!"#(/'*+3!)/!6/(--%77)(!5+/!`MO!5+'+*4)#%!)$('+#&)(#+!Y'+&'!%/!-%$'($*)/Z8!!

19

Stenosi monolaterale dell’arteria renale

Dalla parte del rene stenotico Perfusione renale e GFR

Dalla parte del rene sano Pressione di perfusione renale

RAS, Renina Angiotensina II

Aldosterone

Ipertensione angiotensina II dipendente

RAS soppresso Aumentata escrezione di Na

Blocco del RAS Ridotta pressione arteriosa

Lateralizzazione dopo test diagnostici Il filtrato glomerulare si riduce nel rene stenotico

GFR

normali livelli PRA vena periferica

Page 81: sbobinature nefro_0 - SkyDrive

!

O+!/%!&'+#(&)!?!6)/%'+*%/+3!)/!5)&-(*&(!?!/+77+*4+#'+!5),+*&(3!4%!%4$)%4+#'+!$*+,+5)6)/+8!"#!:1+&'(!-%&(3!+#'*%46)!)!*+#)!-(//%6(*%#(!#+/!$(*'%*+!%,%#')!/%!&'+&&%!%''),)'>G!4%#'+#7(#(!)/!`MO!)$+*%''),(!$+*!4%#'+#+*+!)/!$*($*)(!*)&$+''),(!^k`8!_)!-(#&+71+#2%3!)/!:1%5*(!?!5(4)#%'(!5%//B%2)(#+!&(5)(<*)'+#'),%!5+/!`MOG!&)!%,*>!:1)#5)!)$+*'+#&)(#+!-%1&%'%!&)%!5%//BMV!""!&)%!5%//B+&$%#&)(#+!,(/+4)-%3!-.+!*)&-.)%!5)!$*+-)$)'%*+!)#!+5+4%!$(/4(#%*+!%-1'(3!)#!:1%#'(!)/!/):1)5(!)#!+--+&&(!,%!%5!%--141/%*&)!#+/!-(4$%*')4+#'(!%!4)#(*!$*+&&)(#+8!"#!:1+&'(!-%&(3!)/!6/(--(!0%*4%-(/(7)-(!5+/!`MO!5+'+*4)#%!1#%!/",-"#"),'312'$*()3(%)`^U3!+!/B+00+''(!)$('+#&),%#'+!&)!(''+**>!&(/(!5($(!%5+71%'%!5+$/+2)(#+!,(/+4)-%8!!

!

=(+,$6"#'")R0-.(/'-")

E%!#+0*($%')%!)&-.+4)-%!?!1#!a1"3,$)3')'*01++'-'(*2"),(*"%()-,$*'-")3(,'7"*#()3"%%")0#(*$0')C'%"#(,"%()I$)'*)/$*$,(*(J)5+//B%*'+*)%!*+#%/+8!EB+2)(/(7)%!?!%'+*(&-/+*(')-%!#+//BJPR!5+)!-%&)8!!\(4+!&)!5)-+,%3!/%!-(#5)2)(#+!%'+*(&-/+*(')-%!*+#5+!-(#'(!5)!1#B)4$(*'%#'+!:1('%!5)!$%2)+#')!#+0*($%')-)3!*%$$*+&+#'%#5(!/%!-%1&%!5+/!WS<IPR!5)!)#&100)-)+#2%!*+#%/+!+#5<&'%7+!)#!'+*%$)%!&(&')'1'),%8!E%!$*+,%/+#2%!5)!:1+&'%!-(#5)2)(#+!?!$*(6%6)/4+#'+!4(/'(!$)F!+/+,%'%!5)!:1%#'(!*)&1/')8!!

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

20

Stenosi dell’arteria renale bilaterale o in monorene

attivazione sistema Renina - Angiotensina

Aldosterone

Perfusione renale e GFR

Riduzione dell’escrezione di Na

Blocco del RAS Riduzione anche marcata del filtrato glomerulare

Ridotta pressione arteriosa solo dopo aver ottenuto una deplezione di volume

Espansione di volume

Aumento della pressione arteriosa

Edema polmonare

acuto

Page 82: sbobinature nefro_0 - SkyDrive

"/!-(//%&&(!5+)!7/(4+*1/)!?!1#!+,+#'(!'%*5),(8!!

!

!

!

!

!

!

!

!

!

H*+&+#'%2)(#+!-/)#)-%!

< R*01++'-'(*2"),(*"%()"-1#")3")S;4LR)()0",#"*')H+*-.[!)4$*(,,)&%4+#'+!,)+#+!%!4%#-%*+!)/!4+--%#)&4(!-.+!&'%,%!4%#'+#+#5(!/%!01#2)(#+!*+#%/+3!-)(?!)/!&)&'+4%!*+#)#%<%#7)('+#&)#%8!

< R*01++'-'(*2"),(*"%()6,$&,(00'7")"#!1#!$%2)+#'+!-(#!)$+*'+#&)(#+!#+0*(,%&-(/%*+3!(!-(#!)$+*'+#&)(#+!&+,+*%!+!*+&)&'+#'+!%//%!'+*%$)%3!(!)#!1#!$%2)+#'+!-(#!%'+*(&-/+*(&)!$(/)5)&'*+''1%/+8!

< 46'0$3')3')(3(/")6$%/$*",()"-1#$),'-$,,(*#'))"#!1#!$%2)+#'+!-(#!)$+*'+#&)(#+!4%/!-(#'*(//%'%!+5!)$+*%2('+4)%8!!

\.)%*%4+#'+3!/%!5)%7#(&)!5)00+*+#2)%/+!)#-/15+!&($*%''1''(!/%!*(+,$6"#'")'6(,#(*0'7")Y-)(?3!)/!5%##(!*+#%/+!-%1&%'(!$*)4)'),%4+#'+!5%//B)$+*'+#&)(#+Z!+!/B'6(,#(*0'$*()*(+,$6",(*-.'/"%(3!-)(?!/B)$+*'+#&)(#+!-.+!&)!)#&'%1*%!%!-%1&%!5)!$%'(/(7)+!$%*+#-.)4%/)!*+#%/)8!!

23

Evoluzione della nefropatia ischemica: A) Aterosclerosi aortica di grado lieve; reni con struttura e funzione conservate B) Aterosclerosi progressiva: stenosi arteria renale monolaterale, con ipotrofia del rene, funzione globale conservata per l’aumento del GRF nel rene controlaterale C) L’ulteriore progressione delle lesioni ate- rosclerotiche compromettono entrambi i reni, con evidenti danni strutturali e deficit funzionale.

23

Evoluzione della nefropatia ischemica: A) Aterosclerosi aortica di grado lieve; reni con struttura e funzione conservate B) Aterosclerosi progressiva: stenosi arteria renale monolaterale, con ipotrofia del rene, funzione globale conservata per l’aumento del GRF nel rene controlaterale C) L’ulteriore progressione delle lesioni ate- rosclerotiche compromettono entrambi i reni, con evidenti danni strutturali e deficit funzionale.

23

Evoluzione della nefropatia ischemica: A) Aterosclerosi aortica di grado lieve; reni con struttura e funzione conservate B) Aterosclerosi progressiva: stenosi arteria renale monolaterale, con ipotrofia del rene, funzione globale conservata per l’aumento del GRF nel rene controlaterale C) L’ulteriore progressione delle lesioni ate- rosclerotiche compromettono entrambi i reni, con evidenti danni strutturali e deficit funzionale.

Page 83: sbobinature nefro_0 - SkyDrive

!

L1+&'%!)44%7)#+!-)!&$)+7%!-(4+!)$+*'+#&)(#+3!&'+#(&)!5+//B%*'+*)%!*+#%/+!+5!)#&100)-)+#2%!*+#%/+!-*(#)-%!&)%#(!'*+!-(#5)2)(#)!-.+!$(&&(#(!+&)&'+*+!%1'(#(4%4+#'+3!($$1*+!-(46)#%*&)!)#!,%*)(!4(5(8!_%!#('%*+3!-(41#:1+3!-.+!/%!4%77)(*!$%*'+!5+)!$%2)+#')!-(#!&'+#(&)!5+//B%*'+*)%!*+#%/+!.%!1#B)$+*'+#&)(#+!+&&+#2)%/+3!'%#'B?!-.+!4(/'(!&$+&&(!/%!*),%&-(/%*)22%2)(#+!#(#!5+'+*4)#%!)/!*)+#'*(!5+)!,%/(*)!$*+&&(*)!#+//%!#(*4%8!!

!

S66,$--'$)V'"&*$0#'-$)

>9 <#"C'%',()%5(0'0#(*2")3')1*")0#(*$0')

)

Stenosi dell’arteria renale, ipertensione ed IRC

La maggioranza dei pazienti ipertesi con stenosi dell’arteria renale ha una ipertensione essenziale, come dimostrato dal fatto che l’ipertensione di solito persiste nonostante la rivascolarizzazione

29

Esami finalizzati alla visualizzazione delle arterie renali

•  EcocolorDoppler: Mostra le arterie renali e misura la velocità del flusso come mezzo per valutare la severità della stenosi. E’ economica e largamente disponibile, ma molto legata all’esperienza dell’operatore, alla presenza di obesità o di aria nell’intestino; è meno utile dell’angiografia per la diagnosi di displasia fibromuscolare e di anomalie della arterie renali accessorie. Associata all’ecografia, da informazioni sul parenchima renale. E’ il test di screening per la diagnosi di stenosi dell’arteria renale

•  Angio RMN: Mostra le arterie renali e l’aorta perirenale Il gadolinio non è nefrotossico; è utile nei pazienti con IR; dà immagini eccellenti. E’ costosa: meno utile dell’angiografia invasiva per la diagnosi di displasia fibromuscolare e di anomalie della arterie renali accessorie.

•  Angio TC: Mostra le arterie renali e l’aorta perirenale. Gli stent non sono causa di artefatti. I grandi volumi di mdc richiesti sono potenzialmente nefrotossici.

•  Angiografia: l’angiografia (con o senza sottrazione digitale) è il “golden standard” per la diagnosi di stenosi dell’arteria renale. L’esame viene peraltro in genere eseguito per effettuare l’angioplastica o valutare in maniera ottimale l’anatomia vascolare a scopo chirurgico

Page 84: sbobinature nefro_0 - SkyDrive

A9 <#"C'%',()'%),"66$,#$)#,")'6(,#(*0'$*()()0#(*$0')9,,+*(3!/B)$+*'+#&)(#+!?!-%1&%'%!5%//%!&'+#(&)v!O)!'*%''%!5)!1#B)$+*'+#&)(#+!+&&+#2)%/+!)#!1#!$%2)+#'+!-(#!&'+#(&)!5+//B%*'+*)%!*+#%/+v!O)!'*%''%!5)!1#B)$+*'+#&)(#+!#+0*($%*+#-.)4%/+!)#!1#!$%2)+#'+!-.+3!)#-)5+#'%/4+#'+3!.%!%#-.+!1#%!&'+#(&)!5+//B%*'+*)%!*+#%/+v!!

H+*!,%/1'%*+!)/!*%$$(*'(!'*%!)$+*'+#&)(#+!+!&'+#(&)3!&)!5+,+!&'15)%*+!)/!&)&'+4%!*+#)#%<%#7)('+#&)#%8!

!

!

!

!

!

!

30

Studio del sistema renina-angiotensina

Serve per valutare il rapporto fra stenosi ed ipertensione

Misura della PRA dopo test al captopril Il farmaco determina una riduzione della caduta della pressione

arteriosa distale alla stenosi ed aumenta il rilascio di renina da parte del rene stenotico, ma ha un basso valore predittivo nei confronti dell’ipertensione renovascolare, perché i risultati vengono influenzati da altre condizioni. Il test ha di fatto un valore puramente storico (il test provocativo di primo impiego è oggi la scintigrafia renale).

Angioscintigrafia con test provocativo al captopril Può essere effettuata con 99mTc-MAG3, 99mTc-DTPA o 131I-

Hippuran. La caduta della pressione di perfusione dopo trattamento con Captopril amplifica le differenze di perfusione e funzione renale. Un esame negativo esclude l’ipertensione renovascolare. Ci sono molte limitazioni nei pazienti con creatinina>2.0 mg/dl

32

Misura della PRA nella vena renale: Paragona il rilascio di renina da parte dei due reni; la lateralizzazione (specialmente se associata a soppressione controlaterale) con è un fattore predittivo del miglioramento della pressione arteriosa a seguito della rivascolarizzazione; se la lateralizzazione non c’è questo non significa che la rivascolarizzazione non possa risolvere il problema. I risultati possono comunque essere alterati dai farmaci e da altre condizioni cliniche

Lateralizzazione = renina nel rene ischemico/renina nel rene contro-laterale > 1,5

Soppressione controlaterale = renina nel rene controlaterale – renina nella vena cava infrarenale (cioè periferica) = 0

Questi test vanno interpretati con molta prudenza nella maggior parte dei pazienti anziani con stenosi dell’arteria renale ed ipertensione, dal momento che l’ipertensione non è renina-dipendente ed i risultati non predicono in maniera accurata l’andamento dell’ipertensione dopo la rivascolarizzazione; inoltre i risultati sono influenzati da molte altre condizioni

Page 85: sbobinature nefro_0 - SkyDrive

D9 <#"C'%',()'%),"66$,#$)#,")0#(*$0')3(%%5",#(,'"),(*"%()()3"**$)6",(*-.'/"%()9,,+*(3!)/!5%##(!$%*+#-.)4%/+!?!5)!')$(!)&-.+4)-(3!&+-(#5%*)(!%//%!&'+#(&)v!O)!'*%''%!)#,+-+!5)!1#%!#+0*($%')%!$%*+#-.)4%/+!-(#!%##+&&%!&'+#(&)!5+//B%*'+*)%!*+#%/+v!O)!'*%''%!5)!1#%!#+0*($%')%!)$+*'+#&),%v!

!

!

O+!?!)#5)-%'%!/%!*),%&-(/%*)22%2)(#+3!6)&(7#%!+&&+*+!&)-1*)!-.+!)/!5%##(!$%*+#-.)4%/+!&)%!*+,+*&)6)/+!+!&+-(#5%*)(!%//%!&'+#(&)3!+!#(#!%!$%'(/(7)%!-(#-(4)'%#')!Y+&G!#+0*($%')%!5)%6+')-%Z8!!

!

8(,"6'")

)

)

!

V+*%$)%!4+5)-%!

<!b+)!$%2)+#')!-(#!5)&$/%&)%!0)6*(41&-(/%*+!7/)!S;4)'*'C'#$,'!&(#(!+00)-%-)C!6)&(7#%!$+*N!*)-(*5%*+!-.+!/%!*),%&-(/%*)22%2)(#+!4+5)%#'+!%#7)($/%&')-%!?!)#!7+#+*+!/%!'+*%$)%!5)!&-+/'%!)#!:1+&')!-%&)8!<!!b+)!$%2)+#')!-(#!)$+*'+#&)(#+!+!&'+#(&)!5+//B%*'+*)%!*+#%/+!&1!6%&+!%'+*(&-/+*(')-%3!/B%&$)*)#%3!7/)!)$(/)$+4)22%#')!Y&'%')#+Z!+!/%!-+&&%2)(#+!5+/!014(!&(#(!+&&+#2)%/)8!

33

Studio della funzione renale

•  Misurazione della creatininemia •  Esame delle urine (i pazienti con danno renale ischemico non hanno alterazioni clinicamente rilevanti del sedimento urinario quali

proteinuria o microematuria glomerulare) •  Determinazione del filtrato glomerulare •  Valutazione ecografica delle dimensioni dei

reni

37

Terapia

Obiettivi Opzioni

!   Controllo dell’ipertensione !   Medica

!   Salvataggio del rene

!   Angioplastica senza (displasia fibro-muscolare) o con (aterosclerosi) stenting

!   Trattamento dei disturbi cardiaci (angor, edema polmonare)

!   Rivascolarizzazione chirurgica

Page 86: sbobinature nefro_0 - SkyDrive

<!M\a!)#)6)'(*)!+!6/(--%#')!5+)!*+-+''(*)!5+//B%#7)('+#&)#%!""!&(#(!+00)-%-)!#+/!J;<iIR!5+)!$%2)+#')3!4%!/%!$+*5)'%!5+//%!4%&&%!*+#%/+!+!/%!*)512)(#+!5+//%!$*+&&)(#+!5)!0)/'*%2)(#+!$(&&(#(!$*(51**+!"`!%-1'%!(!-*(#)-%!-.+!?!$('+#2)%'%!5%//%!5+$/+2)(#+!5)!&(5)(3!?!5)!&(/)'(!*+,+*&)6)/+!&+!$*(#'%4+#'+!5)%7#(&')-%'%!+!*%$$*+&+#'%!1#!$*(,%!5+/!0%''(!-.+!?!$*+&+#'+!1#%!4%/%'')%!#+0*(,%&-(/%*+!-*)')-%8!

M#7)($/%&')-%!

EB%#7)($/%&')-%!?!-(#&)5+*%'%!)/!'*%''%4+#'(!5)!&-+/'%!$+*!)!$%2)+#')!-(#!)$+*'+#&)(#+!#(#!-(#'*(//%'%!+!5)&$/%&)%!0)6*(41&-(/%*+8!E%!$*(-+51*%!.%!&1--+&&(!#+//B!JI<WPPR!5+)!$%2)+#')!+!/%!&'+#(&)!*)-(**+!#+/!WP<WWR8!b+)!$%2)+#')!-(#!&'+#(&)!5+//B%*'+*)%!*+#%/+!&1!6%&+!%'+*(&-/+*(')-%!/B%#7)($/%&')-%!.%!1#!6%&&(!'%&&(!5)!&1--+&&)!Y;P<=PRZ3!$+*!-1)!&)!1')/)22%!&+4$*+!/(!&'+#'3!-(#!)/!iP<WPPR!5)!&1--+&&)!+5!1#!WP<ISR!5)!*+&'+#(&)!%5!1#!%##(8!

`),%&-(/%*)22%2)(#+!-.)*1*7)-%!

"/!6o$%&&!+g'*%<%#%'(4)-(!Y)/!6o$%&&!(*)7)#%!5%//%!-+/)%-%!(!5%//%!4+&+#'+*)-%!$)1''(&'(!-.+!5%//B%(*'%Z!,)+#+!+00+''1%'(!#+//BJPR!5+)!-%&)3!/+!%/'*+!'+-#)-.+!Y+&+4$)(!*+)4$)%#'(!5+//B%*'+*)%!*+#%/+Z!#+/!IPR8!E%!4(*'%/)'>!$+*)($+*%'(*)%!,%!5%/!I8W!%/!;8WR8!!M!-)#:1+!%##)!)/!6o$%&&!#(#!?!$)F!01#2)(#%#'+!#+/!;<WJR!5+)!-%&)8!!!!=(+,$6"#'")R6(,#(*0'7"))M66)%4(!$%*/%'(!5)!)$+*'+#&)(#+!-.+!(*)7)#%!5%!$%'(/(7)+!#+0*(,%&-(/%*)!+!5%!$%'(/(7)+!5+/!$%*+#-.)4%!*+#%/+8!M5+&&(!,+5)%4(!-(4+!/B)$+*'+#&)(#+!D!+&&+#2)%/+!(!&+-(#5%*)%!-.+!&)%!<!$(&&%!5+'+*4)#%*+!%!&1%!,(/'%!1#!5%##(!*+#%/+8!"/!5%##(!%#%'(4)-(!-%1&%'(!5%//B)$+*'+#&)(#+!-(/$)&-+!&($*%''1''(!/+!",#(,'(),(*"%')3')6'--$%$)-"%'C,$!+!/+!",#(,'$%(),(*"%'9))

"#!:1+&'%!)44%7)#+!,+5)%4(!#+''%4+#'+!/+!%*'+*)(/+!*+#%/)!-)*-(#5%'+!5%!1#%!&$+&&%!-(/'*+!5)!4%'+*)%/+!+(&)#(0)/(!+!HMO!$(&)'),(G!&)!'*%''%!5)!1#B%/'+*%2)(#+!#('%!-(4+!'"%'*$0'8!E%!)%/)#(&)!%/'*(!#(#!?!-.+!/%!5+$(&)2)(#+!#+/!-(#'+&'(!5+//+!%*'+*)+!5)!$*('+)#+!$/%&4%')-.+3!-.+!&)!%--141/%#(!+!0(*4%#(!:1+&'%!5)&'+&%!5)!4%'+*)%/+!,+'*(&(8!"#!%&&(-)%2)(#+!%!:1+&'(!0+#(4+#(!&)!%&&)&'+!%#-.+!%!+'C,$0')

3(%%5'*#'/"!+!%5!1#!-+*'(!7*%5(!5)!'6(,6%"0'")()'6(,#,$+'")3(%%")/(3'"G!:1+&'(!%&$+''(3!$*+&+#'+!%#-.+!#+)!:1%5*)!5)!)$+*'+#&)(#+!6+#)7#%3!?!$+*N!$*+$(#5+*%#'+!#+/!:1%5*(!5)!%/'+*%2)(#+!,%&-(/%*+!')$)-(!5+//B'6(,#(*0'$*()/"%'&*"G))#&)+4+!%//%!#+-*(&)!0)6*)#()5+8!!!

52

Hyalinosis is evident in the arteriole and interlobular artery in hypertensive nephro- sclerosis, along with mild medial thickening caused by both hypertrophy and hyperplasia of vascular smooth muscle cells. The hyalin material is the result of insudation of plasma proteins, and is pink and glassy-smooth in appearance (ie, hyalin) PAS, X200).

Page 87: sbobinature nefro_0 - SkyDrive

\(#&+71+#2%!5+//%!)%/)#(&)!+!5+//B)$+*$/%&)%!41&-(/%*+!/)&-)%!5+//+!%*'+*)+!5)!$)--(/(!-%/)6*(!+!5+//+!%*'+*)(/+!?!/B%'*(0)%!Y+!-(#&+71+#'+!0)6*(&)Z!5+/!$%*+#-.)4%!*+#%/+3!&)%!%/!/),+//(!5+)!'161/)!-.+!%/!/),+//(!5+)!7/(4+*1/)3!-(#!:1%5*)!5)!&%$/(,1%$0-%(,$0')&%$C"%(8!L1+&'(!0+#(4+#(!?!5+&-*)''(!-(4+!&%$/(,1%$6"#'")'6(,#(*0'7"9))

)

!

!

!

!

!

!

!

!

!

! !

O"*'+(0#"2'$*')-%'*'-.()3(%%")*(+,$0-%(,$0')C(*'&*"G!!!

D L1+//+!5+//z)$+*'+#&)(#+!!D!!X)-*(%/614)#1*)%3!$*('+)#1*)%3!4)-*(+4%'1*)%!D `)512)(#+!5+/!0/1&&(!*+#%/+!+!*)512)(#+!/)+,+<!4(5+*%'%!5+/!^k`3!4%#'+#)4+#'(!

5+//z)$+*'+#&)(#+3!*%*%4+#'+!Y)#!"'%/)%Z!)#&100)-)+#2%!*+#%/+!-*(#)-%!!

O"*'+(0#"2'$*')-%'*'-.()3(%%")*(+,$0-%(,$0')/"%'&*"G!!D!!L1+//+!5+//z)$+*'+#&)(#+!4%/)7#%!YHM_!s!WKP!44l73!5)&'1*6)!#+1*(/(7)-)3!+5+4%!5+//%!$%$)//%3!&-(4$+#&(!-%*5)%-(3!%#+4)%!4)-*(%#7)($%')-%Z8!D!!"#&100)-)+#2%!*+#%/+!%-1'%!(!*%$)5%4+#'+!$*(7*+&&),%3!$*('+)#1*)%!Y%#-.+!#+/!*%#7+!#+0*(&)-(Z3!-)/)#5*1*)%8!!!

!

!

!

!

!

!

!

!

Page 88: sbobinature nefro_0 - SkyDrive

X%/%'')%!`+#%/+!\*(#)-%!

EB)#&100)-)+#2%!*+#%/+!-*(#)-%!?!1#!a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aO`_!.%##(!)#,+-+!1#%!&'(*)%!5)!$%'(/(7)%!*+#%/+!-.+!.%!%,1'(!1#!5+-(*&(!*%$)5%4+#'+!)**+,+*&)6)/+!-.+!/)!.%!$(*'%')!%//%!$+*5)'%!4(/'(!*%$)5%!5+//%!01#2)(#+!*+#%/+8!^+#+*%/4+#'+3!)/!$%2)+#'+!-(#!4%/%'')%!*+#%/+!-*(#)-%!.%!%/'*+!-(4(*6)5)'>!-.+!&)!&(#(!&,)/1$$%'+!)#!-(#&+71+#2%!5+//%!&1%!-(#5)2)(#+3!4+#'*+!)/!$%2)+#'+!-(#!)#&100)-)+#2%!*+#%/+!-%1&%'%!5%!1#!+,+#'(!%-1'(3!)#!'+(*)%3!&$+&&(!#(#!.%!7*(&&)!$*(6/+4)!$+*!)/!*+&'(8!!

E%!4%/%'')%!*+#%/+!-*(#)-%!$1N!+&&+*+!5+0)#)'%!5%!51+!%&$+'')G!

>J U'312'$*()3(%%")+1*2'$*(),(*"%(3!+&$*+&&%!-(4+!,'312'$*()3(%)+'%#,"#$)&%$/(,1%",()"%)3')0$##$)3(%)?@s)3(%)7"%$,()*$,/"%(G)(,,+*(!lZ@)/%E/'*!#(*4%/)22%')!$+*!/%!&1$+*0)-)+!-(*$(*+%8!k(*'1#%'%4+#'+3!&(/(!1#%!$)--(/%!$+*-+#'1%/+!5+)!$%2)+#')!*)+#'*%!)#!:1+&'%!-%'+7(*)%3!)#!:1%#'(!$+*!&-+#5+*+!&(''(!%!:1+&'%!&(7/)%!(--(**+!1#%!4%/%'')%!*+#%/+!-*(#)-%!5)!/1#7%!51*%'%8!!

AJ E%!4%77)(*!$%*'+!5+//+!$+*&(#+!-(#!4%/%'')%!*+#%/+!-*(#)-%3!)#0%'')3!.%!1#!0)/'*%'(!7/(4+*1/%*+!-(#&+*,%'(!(!/+77+*4+#'+!*)5(''(3!$1*!$*+&+#'%#5(!0(&*')()0'*#$/'!5)!4%/%'')%!*+#%/+8!"!&+7#)!$(&&(#(!+&&+*+!0(#5%4+#'%/4+#'+!5)!51+!')$)G!< S*"#$/'-'3!)#'+&)!-(4+!%/'+*%2)(#)!*)&-(#'*%6)/)!%//%!6)($&)%!*+#%/+!(!-(4+!

%/'+*%2)(#)!+,)5+#2)%'+!4+5)%#'+!'+-#)-.+!5)!)4%7)#78!"#!$%*')-(/%*+3!?!')$)-(!)/!*)&-(#'*(!5+//%!,'312'$*()3(%%")/"00")6",(*-.'/"%(G)$*+&+#'+!)#!:1%&)!'1'')!)!$%2)+#')8!M//B+-(7*%0)%3!!&)!*)&-(#'*%#(!"%#(,"2'$*')3(%%5(-$0#,1##1,"),(*"%(3!,)&)6)/)!&($*%''1''(!&+!/B+&%4+!?!-(4$/+'%'(!5%!1#!5($$/+*!-(#!4)&1*%!5+7/)!'*3'-')3'),(0'0#(*2")'*#,",(*"%(3!-.+!5)4(&'*+*>!/B)4$+7#(!$%*+#-.)4%/+!+!4)-*(,%&-(/%*+8!!

< ^1*2'$*"%'3!+,)5+#2)%6)/)!-(#!)#5%7)#)!5)!/%6(*%'(*)(!Y+&%4+!4)-*(&-($)-(!+!0)&)-(<-.)4)-(!5+//+!1*)#+Z8!H+*!+&+4$)(3!$('*+4(!%,+*+!1#%!4)-*(+4%'1*)%3!1#%!$*('+)#1*)%3!1#%!-)/)#5*1*)%3!%/'+*%2)(#)!5+//B+:1)/)6*)(!%-)5(<6%&+!+!-%/-)(<0(&0(*)-(8!

"/!$%2)+#'+!-(#!4%/%'')%!*+#%/+!-*(#)-%3!#(*4%/4+#'+3!$*+&+#'%!1#%!-(&'+//%2)(#+!5)!&+7#)!+!&)#'(4)3!4%!&($*%''1''(!#+//+!0%&)!$*+-(-)!&(#(!4(/'(!)4$(*'%#')!)!$%*%4+'*)!-.+!%66)%4(!%$$+#%!$*+&+#'%'(8!

_),+*&%4+#'+3!/B'*01++'-'(*2"),(*"%()-,$*'-"!?!/%!-$*0(&1(*2")3(%%")/"%"##'"),(*"%()-,$*'-"!+!-(&')'1)&-+!)/!:1%5*(!0)&)($%'(/(7)-(!+!-/)#)-(!-.+!-(#&+71+!%//%!*)512)(#+!)**+,+*&)6)/+!5+//%!4%&&%!$%*+#-.)4%/+!*+#%/+3!+!:1)#5)!%//%!$+*5)'%!$*(7*+&&),%!+!-(#')#1%!5+//+!$*)#-)$%/)!01#2)(#)!5+/!*+#+G!

< ^1*2'$*()(0-,(#,'-()3(%%()0-$,'()"2$#"#()< ^1*2'$*(),(&$%"#,'-()3(%%5$/($0#"0')'3,$(%(##,$%'#'-")

L1+&'(!&)&'+4%!?!%&&(/1'%4+#'+!,)'%/+!+!$*+,+5+!1#%!0)#+!*+7(/%2)(#+!$%*2)%/4+#'+!)#5),)51%/)22%'%!5+//%!-(#-+#'*%2)(#+!5)!-)%&-1#!+/+''*(/)'%!+!5+//%!(&4(/%/)'>!$/%&4%')-%C!'%/+!4+--%#)&4(!$*+,+5+!&+#&(*)!&$+-)%/)22%')!$+*!-)%&-1#!$%*%4+'*(!+!4+--%#)&4)!+00+''(*)!*%$$*+&+#'%')!)#!61(#%!$%*'+!

Page 89: sbobinature nefro_0 - SkyDrive

5%!(*4(#)!+!#+1*('*%&4+'')'(*)3!/%!-1)!%''),)'>!5+'+*4)#%!)/!-(4$(*'%4+#'(!5+/!*+#+!#+)!-(#0*(#')!5+)!,%*)!+/+''*(/)')8!M!0*(#'+!5)!WJP!E!5)!0)/'*%'(!7/(4+*1/%*+!$*(5(''(!(7#)!7)(*#(3!)/!*+#+!*)+&-+!%5!($+*%*+!-(**+2)(#)!4(/'(!%4$)+!-(#!,%*)%2)(#)!5+/!*)%&&(*6)4+#'(!+&'*+4%4+#'+!$)--(/+8!

< ^1*2'$*')(*3$-,'*()H*(512)(#+!5+//%!,)'%4)#%!_!#+//%!&1%!0(*4%!%''),%8!!H*(512)(#+!5)!+*)'*($()+')#%8!!H*(512)(#+!5)!&(&'%#2+!+5!%1'%-()5)!-%$%-)!5)!*+7(/%*+!/+!*+&)&'+#2+!,%&-(/%*)!&)&'+4)-.+!Y*+#)#%3!+#5('+/)#%cZ!

T#%!*)512)(#+!5+//%!01#2)(#+!*+#%/+!&)!*)0/+''+!'*)/$3$)3'7(,0$)&1)!$%*%4+'*)!-.+!%66)%4(!-)'%'(8!

WZ!H+*!0%*+!3'"&*$0')3')RU;3!5(66)%4(!%#2)'1''(!+",()3'"&*$0')3')'*01++'-'(*2"),(*"%(G)(,,+*(!-$*+(,/",()%"),'312'$*()3(%)+'%#,"#$)&%$/(,1%",(8!E%!&')4%!5+/!0)/'*%'(!7/(4+*1/%*+3!%''1%/4+#'+3!,)+#+!+00+''1%'%!-(#!)!&+71+#')!4+'(5)G!

< ;,("#'*(/'")< ;%(","*-()3(%%")-,("#'*'*")< ^$,/1%(!Y\(-]-*(0'<^%1/'!U!X_`_Z)

E%!-/+%*%#-+!5+//%!-*+%')#)#%3!-(4+!%66)%4(!7)>!5+''(3!.%!)/!51$/)-+!$*(6/+4%!5)!+&&+*+!&$+&&(!5)00)-)/4+#'+!%''1%6)/+!%!-%1&%!5+//%!#+-+&&)'>!5+//%!*%--(/'%!5+//+!1*)#+3!+!5)!+&&+*+!%#-(*%!#(#!6+#!&'%#5%*5)22%'%3!-(&)--.[!&)!$(&&(#(!*+7)&'*%*+!,%*)%2)(#)!%#-.+!#('+,(/)!'*%!1#!/%6(*%'(*)(!+!/B%/'*(8!

b+/!$%2)+#'+!-(#!4%/%'')%!*+#%/+!-*(#)-%3!-(41#:1+3!/B%&$+''(!-.+!%!#()!)#'+*+&&%!?!/%!,%/1'%2)(#+!5+//B"*3"/(*#$)#(/6$,"%(!5+/!5+-%5)4+#'(!5+//%!01#2)(#+!*+#%/+G!(,,+*(3!&)%4(!)#'+*+&&%')!%!-%$)*+!&+!)!&1()!$%*%4+'*)!5)!01#2)(#%/)'>!*+#%/+!Y$)F!(!4+#(!%/'+*%')Z!&)!4%#'+#7(#(!&'%6)/)!#+/!'+4$(!!(!&+!)#,+-+!/%!$+*5)'%!5+//%!01#2)(#%/)'>!*+#%/+!.%!1#!-(4$(*'%4+#'(!+,(/1'),(!$)F!(!4+#(!%--+/+*%'(8!O1//%!6%&+!5)!:1+&'+!(&&+*,%2)(#)!&)!4(5)0)-%!)/!#(&'*(!-(4$(*'%4+#'(!'+*%$+1')-(8!

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

!

KZ H+*!$('+*!5)4(&'*%*+!-(#!-+*'+22%!/%!$*+&+#2%!5)!4%/%'')%!*+#%/+!D!'*%/%&-)%#5(!/%!6)($&)%3!:1%&)!4%)!)#5)-%'%!#+/!$%2)+#'+!-(#!*)512)(#+!5+//%!01#2)(#+!*+#%/+3!(--(**+!*)/+,%*+!/B"%#(,"2'$*()3(%%")/$,+$%$&'"),(*"%(9!T#%!,(/'%3!4%!%!,(/'+!%#-(*%!(77)3!$1N!+&&+*+!1')/+!/%!5)4(&'*%2)(#+!5+//B$0#($3'0#,$+'"),(*"%(3!1#%!$%*')-(/%*+!%/'+*%2)(#+!&-.+/+'*)-%!-.+!5+*),%!5%//(!&:1)/)6*)(!5+//B(4+(&'%&)!-%/-)(<0(&0(*)-%!-%1&%'%!5%//B)#&100)-)+#2%!*+#%/+8!!

!

QZ 9,,)%4+#'+3!(--(**+!$()!0%*+!3'"&*$0')(2'$%$&'-"3!(,,+*(!5+0)#)*+!:1%/+!&)%!/%!4%/%'')%!*+#%/+!-*(#)-%!-.+!&'%!5+'+*4)#%#5(!/B)#&100)-)+#2%!*+#%/+!-*(#)-%8!

Page 90: sbobinature nefro_0 - SkyDrive

L1+&'(!$1N!+&&+*+!0%''(!$*)4%!5)!'1''(!5%/!$1#'(!5)!,)&'%!-/)#)-(G!/%!4%/%'')%!*+#%/+!-*(#)-%!$1N!%,+*+!1#%!&+*)+!5)!&)#'(4)!@$(&)'),)AG!$+*!+&+4$)(3!$1N!5+'+*4)#%*+!$*('+)#1*)%3!)$+*'+#&)(#+!&+,+*%3!-(4$/)-%2)(#)!,%*)+8!L1+&'(3!%#-.+!$+*-.[!%!&+-(#5%!5+/!')$(!5)!$%'(/(7)%!$*+&+#'+!&)!4(5)0)-.+*>!5)!-(#&+71+#2%!)/!#(&'*(!%''+77)%4+#'(!'+*%$+1')-(8!

!

^*%5)#7!

"#5)$+#5+#'+4+#'+!5%//B+2)(/(7)%3!?!)4$(*'%#'+!,%/1'%*+!/%!&,"7'#:!5+/!:1%5*(!-/)#)-(!-/%&&)0)-%#5(/(!&+-(#5(!1#(!&-.+4%!5+0)#)'(!)#'+*#%2)(#%/4+#'+8!b+/!-%&(!5+//%!4%/%'')%!*+#%/+!-*(#)-%3!&(#(!&'%')!5+0)#)')!S!&'%5)G!

>9)<$&&(##$)"),'0-.'$)3')*(+,$6"#'")I(09)3'"C(#'-$J)$77(,$)-$*)/"%"##'"),(*"%()-,$*'-")'*)"##$)()+1*2'$*(),(*"%()-$*0(,7"#")I`^U)N)t@)/%E/'*)-$,,(##$)6(,)016(,+'-'()-$,6$,("J)

A9)O"%"##'"),(*"%()-,$*'-")'*)"##$)-$*)%'(7(),'312'$*()3(%)`^U)Iet)L)Z@)/%E/'*J)

"!$%2)+#')!0)#(!%/!&+-(#5(!&'%5)(!#(#!.%!&+7#)!(!&)#'(4)!5)!)#&100)-)+#2%!*+#%/+!*)/+,%6)/)!%7/)!+&%4)!5)!/%6(*%'(*)(3!+!#(#!.%##(!$*(6/+4%')-.+!-/)#)-.+!/+7%'+!%//B)#&100)-)+#2%!*+#%/+8!!

D9)R*01++'-'(*2"),(*"%()/$3(,"#")I`^U)?t)L)D@)/%E/'*J)

B9)R*01++'-'(*2"),(*"%()0(7(,")I`^U)At)L)>?)/%E/'*J)

?9)R*01++'-'(*2"),(*"%()#(,/'*"%()I`^U)l)>?)/%E/'*)$)#(,"6'")0$0#'#1#'7"J)

O)7#)0)-%'(!-/)#)-(G!/B1,(/'"G)$77(,$)'%)a1"3,$)-%'*'-$)-"10"#$)3"%%5'*01++'-'(*2"),(*"%(G)-.+!$1N!+&&+*+!-1*%'%!+&-/1&),%4+#'+!-(#!/%!'+*%$)%!&(&')'1'),%!Ym!5)%/)&)Z3!&)!$*+&+#'%!&(/(!#+)!$%2)+#')!-(#!^k`!0(*'+4+#'+!*)5(''(8!L1%/-.+!5)&'1*6(!$1N!!+&&+*+!$*+&+#'+!%#-.+!#+7/)!&'%5)!$*+-+5+#')3!4%!$1N!+&&+*+!-(#'*(//%'(!&+#2%!)/!*)-(*&(!%//%!5)%/)&)8!"/!$%2)+#'+!-(#!0)/'*%'(!7/(4+*1/%*+!&1$+*)(*+!%)!;P!4/U4)#U&1$+*0)-)+!-(*$(*+%!$1N!%,+*+!)!&+7#)!5+//%!4%/%'')%!5)!6%&+!+!*$*).")0(&*')3')'*01++'-'(*2"),(*"%(9!"/!$%2)+#'+!-(#!^k`!4(5+*%'%4+#'+!(!&+,+*%4+#'+!*)5(''(3!*$*)i)"*-$,")1,(/'-$!4%!5),+*&+!%/'+*%2)(#)!-.+!#+/!/(*(!)#&)+4+!&(#(!5+0)#)'+!-$/6%'-"*2()3(%%5'*01++'-'(*2"),(*"%(G)$+*-.[!$1*!+&&+#5(!-(#&+71+#2+!5+//B)#&100)-)+#2%!*+#%/+!$*+&+#'%#(!-(41#:1+!1#!/(*(!7*%5(!5)!&$+-)0)-)'>!+5!%1'(#(4)%!Y+&G!)$+*'+#&)(#+3!%#+4)%3!5)&'1*6)!5+/!4+'%6(/)&4(!+/+''*(/)')-(3!5)&'1*6)!(&'+(4+'%6(/)-)Z8!"!$%2)+#')!-(#!)#&100)-)+#2%!*+#%/+!$(&&(#(!$*+&+#'%*+!#1##(G)"%-1*()$)0$%$)1*"!5)!:1+&'+!-(4$/)-%#2+3!+5!+&&+!-)!$+*4+''(#(!D!-(4+!&)!5)-+,%!D!5)!)5+#')0)-%*+!/%!4%/%'')%!*+#%/+8!"/!$*(6/+4%!?!-.+!:1+&'+!-(#5)2)(#)!*$*)*(-(00",'"/(*#(!5+,(#(!+&&+*+!-%1&%'+!5%//%!$%'(/(7)%!*+#%/+!Y&)!$+#&)3!$+*!+&+4$)(3!%//B%#+4)%!+!%//B)$+*'+#&)(#+Z3!+!:1)#5)!*)-.)+5(#(!1#%!-+*'%!:1('%!5)!%$$*(0(#5)4+#'(!5)%7#(&')-(!%//(!&-($(!5)!$(**+!1#%!5)%7#(&)!&$+-)0)-%!+5!)#'+*,+#')!'+*%$+1')-)!&$+-)0)-)8!H+*!+&+4$)(3!$+#&)%4(!%//B%#+4)%G!:1+//%!5%!)#&100)-)+#2%!*+#%/+!D!#(*4(-*(4)-%3!#(*4(-)')-%3!)$(*)7+#+*%'),%!<!&)!5+,+!'*%''%*+!-(#!/B+*)'*($()+')#%!$+*-.[!5+*),%!5%/!,+#)*!4+#(!5+//%!01#2)(#+!+#5(-*)#%!5+/!*+#+8!X%!1#B%#+4)%!$1N!+&&+*+!-%1&%'%!5%!4(/')!%/'*)!0%''(*)!Y&)5+*($+#)-%!5%!-%*+#2%!5)!0+**(!(!5%!&%#71)#%4+#'(!-*(#)-(!^"3!4%-*(-)')-%!5%!-%*+#2%!5)!0(/%')3!+--cZ!+!)#!:1+&')!-%&)!/%!'+*%$)%!5+,+!+&&+*+!5),+*&%8!

a$)5+4)(/(7)%!+!$*(6/+4)!

Page 91: sbobinature nefro_0 - SkyDrive

E+!4%/%'')+!*+#%/)!-*(#)-.+!&(#(!)4$(*'%#')!$+*!51+!*%7)(#)!0(#5%4+#'%/)8!E%!$*)4%!*%7)(#+!?!-.+3!%#-.+!&+!/%!4%/%'')%!*+#%/+!'+*4)#%/+!)#'+*+&&%!&(/(!SP8PPP!$+*&(#+!)#!"'%/)%3!)/!&1(!-(&'(!&%#)'%*)(!?!+&(*6)'%#'+8!E%!'+*%$)%!5)%/)')-%3!-(#!'1''(!-)N!-.+!/+!?!%##+&&(3!-(&'%!-)*-%!;P8PPP!+1*(!%//B%##(!$+*!(7#)!$%2)+#'+3!+!$+&%!&1/!OOb!$+*!)/!WPR!5+//%!&$+&%!&%#)'%*)%!'('%/+8!!

"/!&+-(#5(!$*(6/+4%!)4$(*'%#'+3!&($*%''1''(!5%/!IPPP!)#!$()3!?!:1+//(!5+//%!5)001&)(#+!&+4$*+!$)F!%4$)%!5+)!$%2)+#')!-(#!4%/%'')%!*+#%/+!-*(#)-%!#+7/)!&'%')!W3!I3!K!+!Q8!"#!"'%/)%!-)*-%!S!4)/)(#)!5)!$+*&(#+!&(#(!%00+''+!5%!4%/%'')%!*+#%/+!-*(#)-%8!

!

L1+&'(!?!$*(6/+4%')-(!&($*%''1''(!$+*!1#%!*%7)(#+G!&+!?!,+*(!-.+!-B?!1#!-+*'(!*)&-.)(!5)!+,(/12)(#+!,+*&(!/BaO`_3!1#!$*(6/+4%!%#-(*%!$)F!)4$(*'%#'+!?!:1+//(!*+/%'),(!%//B"1/(*#"#$),'0-.'$)-",3'$7"0-$%",(!#+)!$%2)+#')!-(#!)#&100)-)+#2%!*+#%/+!-*(#)-%8!"/!*)&-.)(!%14+#'%!%/!$*(7*+5)*+!5+//(!&'%5)(!5)!4%/%'')%G!)/!$%2)+#'+!-(#!4%/%'')%!*+#%/+!-*(#)-%!&+#2%!)#&100)-)+#2%!*+#%/+!.%!1#!*)&-.)(!*+/%'),(!-%*5)(,%&-(/%*+!$%*)!%!I<Q!,(/'+!:1+//(!5+//%!$($(/%2)(#+!7+#+*%/+8!"/!5)%6+')-(3!$()3!?!-(#&)5+*%'(!-(4+!%,+#'+!1#!(a1'7"%(*#()-",3'$7"0-$%",(9!E%!4%/%'')%!*+#%/+!-*(#)-%!?!+#'*%'%!$*+$('+#'+4+#'+!'*%!)!0%''(*)!5)!*)&-.)(!-%*5)(,%&-(/%*)3!$(#+#5(&)!&(&'%#2)%/4+#'+!"%)6,'/$)6$0#$)'*%!)!0%''(*)!5)!*)&-.)(!4%77)(*)8!"/!*)&-.)(!5)!+,+#'(!-%*5)(,%&-(/%*+!)#!1#!$%2)+#'+!-(#!4%/%'')%!*+#%/+!-*(#)-%!+5!)#&100)-)+#2%!*+#%/+!?!7*(&&(/%#%4+#'+!:1%#')0)-%6)/+!)#'(*#(!S<WP!,(/'+!:1+//(!5+//%!$($(/%2)(#+!7+#+*%/+8!"/!*)&-.)(!5)!+,+#')!\h!)#!1#!$%2)+#'+!-(#!)#&100)-)+#2%!*+#%/+!'+*4)#%/+!)#!'+*%$)%!&(&')'1'),%!?!$%*)!%!=P<WIP!,(/'+!:1+//(!5+//%!$($(/%2)(#+!7+#+*%/+G!:1+&'(!&)7#)0)-%!)#!&(/5(#)!1#!*)&-.)(!5+/!WPR!%##1(8!!

L1+&'(!&$)+7%!-(4+!4%)3!%!0*(#'+!5)!-(&e!'%#'+!$+*&(#+!-.+!&(00*(#(!5)!4%/%'')%!*+#%/+!-*(#)-%!-(#!)#&100)-)+#2%!*+#%/+3!&(/(!$(-.+!&)%#(!:1+//+!)#!5)%/)&)G!41()(#(!$*)4%8!!

!

!

!

!

!

Prevalenza singoli stadi Stadio GFR

Prevalenza USA %

Stima Italia

1 Danno renale

con GFR normale o !

> 90 3.3 2.000.000

2 Danno renale

con GFR lievemente "

60-89 3.0 1.800.000

3 Moderata " GFR 30-59 4.3 2.500.000

4 Severa " GFR 15-29 0.2 100.000

5 Insufficienza

renale terminale

<15 o dialisi 0.1 4-50.000

Page 92: sbobinature nefro_0 - SkyDrive

X%/%'')%!*+#%/+!-*(#)-%!+!*)&-.)(!-%*5)(,%&-(/%*+!

"/!/+7%4+!'*%!4%/%'')%!*+#%/+!-*(#)-%!+5!+,+#')!-%*5)(,%&-(/%*)!&)!%*')-(/%!)#!$)F!$1#')8!E%!4%/%'')%!*+#%/+!-*(#)-%!)#!:1%#'(!'%/+3!$+*!$*)4%!-(&%3!%14+#'%!5)!$+*!&[!)/!*)&-.)(!-%*5)(,%&-(/%*+!$+*!*%7)(#)!#(#!#('+8!

"#!&+-(#5(!/1(7(3!/%!4%/%'')%!*+#%/+!-*(#)-%!&)!%&&(-)%!%5!1#%!&+*)+!5)!-(#5)2)(#)!D!%-)5(&)3!&'%'(!)#0)%44%'(*)(!-*(#)-(3!5)&/)$)5+4)%3!)$+*'+#&)(#+!D!-)%&-1#%!5+//+!:1%/)!i)+"##$,()3'),'0-.'$)-",3'$7"0-$%",(9)

!

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

"!0%''(*)!5)!*)&-.)(!\h!&)!5),)5(#(!)#!/"&&'$,')+!/'*$,'8!"!4%77)(*)!&(#(!:1+//)!-.+!.%##(!1#B%&&(-)%2)(#+!)#5)$+#5+#'+!5%/!$1#'(!5)!,)&'%!&'%')&')-(!-(#!/B+,+#'(8!L1%/(*%!1#!0%''(*+!5)!*)&-.)(!4%77)(*+!&)%!-(**+77)6)/+!D!/%!&1%!-(**+2)(#+!5+'+*4)#%!1#%!*)512)(#+!+00+''),%!5+/!*)&-.)(8!"!0%''(*)!4%77)(*)!&(#(!)!&+71+#')8!b(#!-(**+77)6)/)G!

< a'>!< O+&&(!4%&-.)/+!< O'(*)%!0%4)/)%*+!5)!4%/%'')%!-%*5)(,%&-(/%*+!Y)#'+&%!-(4+!+,+#')!\h!$*+-(-)3!

jSS!%##)!&+!1(4(C!j;S!%##)!&+!5(##%Z!

^/)!%/'*)!0%''(*)!4%77)(*)3!-(**+77)6)/)G!

< h%/(*)!5)!-(/+&'+*(/(!YE_E3!l_E3!'('%/+Z!< "$+*'+#&)(#+!< k14(!5)!&)7%*+''%!< _)%6+'+!Y)#!*+%/'>3!-(#&)5+*%'(!+:1),%/+#'+!\hZ!< X%/%'')%!*+#%/+!-*(#)-%!

fattori di rischio CV specifici o influenzati dell’uremia

!   Tipo di malattia renale !   Livello di GFR !   Proteinuria !   Attività del sistema RAA !   Aumento del volume del liquido extracellulare !   Alterazioni del metabolismo Ca-P !   Dislipidemia

!  bassi livelli di HDL colesterolo !  alti livelli di particelle VLDL remnants” e di IDL ricche di trigliceridi !  prevalenza di LDL piccole e dense !  aumento dei livelli di Lp(a)

!   Anemia !   Malnutrizione !   Infiammazione cronica (alti livelli di molecole proinfiammatorie e di adesione quali Il-6, TNF-!, IFN-", PCR, ICAM-1, VCAM-1, selectina-E) !   Ipercoagulabilità !   Stress ossidativo !   Alti livelli di omocisteina !   Tossine uremiche

KDQOI, modificato da NCPE Adult Treatment Panel III

Page 93: sbobinature nefro_0 - SkyDrive

a&)&'(#(!$()!)!0%''(*)!4)#(*)3!5+0)#)')!-(4+!0%''(*)!$+*!)!:1%/)!+&)&'+!1#B%&&(-)%2)(#+!+$)5+4)(/(7)-%3!4%!$+*!)!:1%/)!#+&&1#(!?!*)1&-)'(!%!5)4(&'*%*+!-.+!D!)#'+*,+#+#5(!&1!5)!+&&)!D!&)!*)51-%!+00+''),%4+#'+!)/!*)&-.)(!\h8!

L1)#5)3!0(-%/)22%*&)!&1/!*)&-.)(!-%*5)(,%&-(/%*+!+!&1//%!&1%!-(**+2)(#+!?!1#!(6)+''),(!)4$(*'%#')&&)4(!#+/!4%#%7+4+#'!5+)!$%2)+#')!-(#!4%/%'')%!*+#%/+!-*(#)-%!+!5+,+!+&&+*+!$+*&+71)'(!)#!(7#)!4(4+#'(!5+//%!&'(*)%!#%'1*%/+8!

!

H*(7*+&&)(#+!5+//%!4%/%'')%!*+#%/+!-*(#)-%!

E%!4%/%'')%!*+#%/+!.%!/%!&1%!&'(*)%!#%'1*%/+!+!/%!&1%!'+#5+#2%!%!$*(7*+5)*+!,+*&(!/(!&'%5)(!'+*4)#%/+8!d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

!

"/!$*)4(!%&$+''(!)4$(*'%#'+!5+//%!$*(7*+&&)(#+!?!:1+//(!*+/%'),(!%//+!-"6"-'#:)3')"3"##"/(*#$)3(%),(*()"%%"),'312'$*()3(%%")6$6$%"2'$*()*(+,$*'-"9!"/!*+#+!?!1#!(*7%#(!-(&')'1)'(!5%!1#!)#&)+4+!5)!1#)'>!01#2)(#%/)!)#5)$+#5+#')3!)!#+0*(#)8!E%!*)&$(&'%!

Prog

ress

ione

del

la n

efro

pati

a

blocco RAA, riduzione PA

fattori del complemento,

ecc.

Page 94: sbobinature nefro_0 - SkyDrive

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

<')7(,'+'-")1*")7"0$-$0#,'2'$*()3(%%5",#(,'$%")(++(,(*#(3!-.+!0%!&e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d)-$*),'#(*2'$*()3')"-a1")()0$3'$)d)%''),%!)!*+-+''(*)!5)!$*+&&)(#+!+!,(/14+!-.+3!'*%4)'+!,)+!%00+*+#')!%1'(#(4)-.+!+!-)*-1)')!5)!)#'+7*%2)(#+3!&(#(!$()!)#!7*%5(!5)!4(5)0)-%*+!/B%&&+''(!(*4(#%/+!Y+#5('+/)#%3!MbH3!MV""Z!)#!4(5(!'%/+!5%!$*(,(-%*+!/%!4(5)0)-%2)(#+!+4(5)#%4)-%!%!/),+//(!7/(4+*1/%*+8!\(#&+71+#2%!5)!:1+&'(!0+#(4+#(!?!/%!-(4$%*&%!5)!'6(,#(*0'$*()&%$/(,1%",(9)V%/+!-(#5)2)(#+!.%!51+!-(#&+71+#2+G!

< ;$*0(&1(*2")3',(##")01%)&%$/(,1%$!E+!-+//1/+!7/(4+*1/%*+!)#-%$%-)!5)!*+$/)-%2)(#+3!)!$(5(-)')3!&(''($(&')!%//(!&'*+&&!5+//B)$+*0)/'*%2)(#+3!,%##(!)#-(#'*(!%5!%/'+*%2)(#)!+5!)#0)#+!%//%!4(*'+3!'%#'B?!,+*(!-.+!/%!/+&)(#+!%#%'(4)-%!7/(4+*1/%*+!-.+!0%!&+71)'(!%//B)$+*'+#&)(#+!7/(4+*1/%*+!&$+*)4+#'%/+!#+/!*%''(!?!4(/'(!&)4)/+!%//%!7/(4+*1/(&-/+*(&)8!

< ;$*0(&1(*2")")%'7(%%$)#1C1%",()b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e@)+3!-(#!$*('+)#1*)%!)4$(*'%#'+!?!/(*$)3')>A?Ef?9))

Page 95: sbobinature nefro_0 - SkyDrive

"#!&+-(#5(!/1(7(3!(/'*+!-.+!&1//%!$*+&&)(#+!%*'+*)(&%!&)&'+4)-%3!5(66)%4(!%7)*+!&1/!#$*$)3(%%5",#(,'$%")(++(,(*#(3!(6)+''),(!-.+!$(&&)%4(!*%77)1#7+*+!-(#!S;4LR)+!0",#"*'9)!

H(&&)%4(!%#-.+!/$*'#$,",(!/B+00)-%-)%!5+//%!'+*%$)%!+!:1)#5)!/B%#5%4+#'(!5+//%!4%/%'')%G!:1+&'(!?!$(&&)6)/+!,%/1'%#5(!/B"*3"/(*#$)3(%%")6,$#('*1,'"8!L1)#5)3!)#)2)%4(!/%!'+*%$)%!%**),%#5(!7*%51%/4+#'+!%/!5(&%77)(!+00)-%-+!5)!M\a<"!(!&%*'%#(G!&+!#(#!(''+#)%4(!)/!*)&1/'%'(!5+&)5+*%'(!&1//%!$*('+)#1*)%3!%77)1#7)%4(!1#!%/'*(!0%*4%-(!%#%/(7(!Y&%*'%#(3!&+!%66)%4(!-(4)#-)%'(!-(#!1#!M\a<"3!($$1*+!\\qZ8!O+!#(#!(''+#)%4(!%#-(*%!*)&1/'%')!&(55)&0%-+#')3!%77)1#7)%4(!1#!'+*2(!0%*4%-(!)$('+#&),%#'+3!4+7/)(!&+!1#!3'1,(#'-$3!%//(!&-($(!5)!*)51**+!/B)$+*'+#&)(#+!%*'+*)(&%8!

a&)&'(#(!5%')!-.+!,%/(*)22%#(3!#+//+!&)'1%2)(#)!+&'*+4+3!%/-1#)!')$)!5)!)#'+*,+#')!&1$$/+4+#'%*)G!

< S*#"&$*'0#'),(-(##$,'"%')3(%%5"%3$0#(,$*()YO$)*(#(/%''(#+3!a$/+*+#(#+3!\%#*+(#(%'(Z!

< V'(#")'6$6,$#('-"!H+*!/1#7.)&&)4(!'+4$(!?!&'%'(!-(#&)5+*%'(!1#!)#'+*,+#'(!-%*5)#+!)#!#+0*(/(7)%G!(77)!&)!4+''+!0(*'+4+#'+!)#!5)&-1&&)(#+!/%!&1%!+00+''),%!1')/)'>8!

< U(0#,'2'$*()0$3'-")< <#"#'*()!

b+/!$%2)+#'+!*$*)6,$#('*1,'-$3!:1+&')!)#'+*,+#')!'+*%$+1')-)!&(#(!1')/)!#+/!*)51**+!)/!*)&-.)(!-%*5)(,%&-(/%*+3!4%!#(#!*)51-(#(!)/!*)&-.)(!5)!$*(7*+&&)(#+!%5!)#&100)-)+#2%!*+#%/+!'+*4)#%/+8!"#!(7#)!-%&(3!%#-.+!&(/(!/%!*)512)(#+!5+/!*)&-.)(!-%*5)(,%&-(/%*+!?!5)!,%/(*+!%&&(/1'(3!$()-.[!-)!$+*4+''+!5)!*)51**+!/+!-(4(*6)5)'>!5)!:1+&')!$%2)+#')8!"#!-(#-*+'(!:1+&'(!&)7#)0)-%G!

< X)7/)(*+!&($*%,,),+#2%!%!/1#7(!'+*4)#+!< X)#(*!-(&'(!&%#)'%*)(!

a3!#+)!$%2)+#')!$*('+)#1*)-)3!6$00'C'%'#:)3'),"%%(*#",()%")6,$&,(00'$*()3(%%5'*01++'-'(*2"),(*"%()-,$*'-"G)-(#!4)#(*+!*)-(*&(!%//%!5)%/)&)!+!7*%#5+!*)&$%*4)(!5%/!$1#'(!5)!,)&'%!5)!-(&'(!&%#)'%*)(8!

!

;$/6%'-"*2()3(%%5'*01++'-'(*2"),(*"%()

E+!-(4$/)-%#2+!5+//B)#&100)-)+#2%!*+#%/+!&(#(!4(/'+$/)-)!+!&(#(!/+7%'+3!%//%!*)'+#2)(#+!5+)!$*(5('')!0)#%/)!5+/!-%'%6(/)&4(!%2('%'(3!%//+!%/'+*%2)(#)!4+'%6(/)-.+!-.+!&)!,+*)0)-%#(!%!-%1&%!5+//%!4%#-%'%!$*(512)(#+!5)!(*4(#)!+!%/'*+!&(&'%#2+!%/!/),+//(!*+#%/+!+!%//%!*)512)(#+!5+//%!-%$%-)'>!5)!*+7(/%2)(#+!5+//B(4+(&'%&)!)5*(+/+''*(/)')-%8!!

O(&'%#2+!-.+!,+#7(#(!0)/'*%'+!+5!+/)4)#%'+!+&-/1&),%4+#'+!5%/!*+#+!Y+&G!-*+%')#)#%Z!&)!%--141/%#(!$*(7*+&&),%4+#'+!)#!6%&+!%//%!*)512)(#+!5+//%!01#2)(#+!*+#%/+8!_%/!$1#'(!5)!,)&'%!5)!6)(-.)4)-%!-/)#)-%3!:1+&'+!&(&'%#2+!&)!'*(,+*%##(!%14+#'%'+!#+/!&%#71+!-(#!1#!%#5%4+#'(!-.+!$*+,+5+!)/!*%55($$)%4+#'(!5+//%!/(*(!-(#-+#'*%2)(#+!%5!(7#)!5)4+22%4+#'(!5+//%!01#2)(#+!*+#%/+8!5%/!$1#'(!5)!,)&'%!0)&)($%'(/(7)-(3!a1"*3$)0'),"&&'1*&$*$)%'7(%%')#$00'-'))/!$%2)+#'+!&,)/1$$%!1#%!&)#'(4%'(/(7)%8!!

M/'*+!&(&'%#2+!&(#(!&(/(!6",2'"%/(*#(!*+7(/%'+!5%/!*+#+3!+!)!0(&0%')!&(#(!1#!+&+4$)(!')$)-(8!"!0(&0%')!&(#(!%&&(*6)')!5%//%!5)+'%!+!&(#(!+/)4)#%')!5%)!*+#)3!4%!)!/(*(!/),+//)!&(#(!*+7(/%')!%#-.+!5%//+!6","#',$'3'G)-)(?!5%)!/),+//)!5)!HVl8!"/!HVl!?!$*(5(''(!)#!*)&$(&'%!%//B%14+#'(!5+//%!-(#-+#'*%2)(#+!5)!0(&0%')!+!%7)&-+!C%$--"*3$)%5"00$,C'/(*#$)'161/%*+!

Page 96: sbobinature nefro_0 - SkyDrive

$*(&&)4%/+!5)!0(&0%'(3!-(&)--.[!)!/),+//)!5)!0(&0%')!&)!4%#'+#7(#(!#(*4%/)!0)#-.[!#(#!)#'+*,)+#+!1#!0%''(*+!-.+!5)&'1*6%!:1+&'%!*+7(/%2)(#+!

E%!'+*2%!-%'+7(*)%!5)!&(&'%#2+!?!:1+//%!5+//+!&(&'%#2+!5('%'+!5)!1#%!*+7(/%2)(#+!:1%&)!$+*0+''%G!"-a1")()0$3'$CG)6(,)(0(/6'$9)"/!&(77+''(!-(#!)#&100)-)+#2%!*+#%/+!*$*)6,(0(*#"),'#(*2'$*()6,$&,(00'7")3')"-a1")()0$3'$!-(#!)/!$*(7*+&&),(!5+-/)#(!5+//%!01#2)(#+!*+#%/+8!L1+&'(!?!6)(/(7)-%4+#'+!)#5)&$+#&%6)/+!$+*!/%!,)'%3!%/'*)4+#')!&)!%--141/+*+66+*(!+#(*4)!:1%#')'>!5)!%-:1%!+!&(5)({!EB(*7%#)&4(!?!5('%'(!5)!5),+*&)!&)&'+4)!(4+(&'%')-)!$+*!%-:1%!+!&(5)(!'%/)!5%!#(#!$+*5+*+!$*%')-%4+#'+!4%)!/%!-%$%-)'>!5)!*+7(/%2)(#+3!-.+!?!4%#'+#1'%!0)#(!%//(!&'%5)(!'+*4)#%/+8!E%!-%$%-)'>!5)!4%#'+#)4+#'(!5+//B(4+(&'%&)!)5*(&%/)#%!,+**+66+!$+*51'%!&(/(!#+/!-%&(!5)!1#%!&)'1%2)(#+!5)!)#&100)-)+#2%!*+#%/+!'+*4)#%/+!#(#!'*%''%'%!-(#!/%!5)%/)&)!D!4%!)#!:1+&'(!-%&(!)/!$%2)+#'+!4(*)*+66+!$*)4%!%!-%1&%!5+//%!*)'+#2)(#+!5+)!-%'%6(/)')!%2('%')8!b+//B'*01++'-'(*2"),(*"%()"-1#")0')7(,'+'-")%5(0"##$)-$*#,",'$Q)/%!*)'+#2)(#+!5+//+!&-(*)+!&)!&,)/1$$%!#+//B%*-(!5)!7)(*#)3!4+#'*+!/%!*)'+#2)(#+!)5*(&(5)-%!?!6,"#'-"/(*#()'//(3'"#"9)

!

V(+'-'#)3')(%'/'*"2'$*() ;$*0(&1(*2()

`)'+#2)(#+!5+)!$*(5('')!'+*4)<#%/)!5+/!4+'%6(/)&4(!%2('%'(!Y1*+%3!-*+%')#)#%3!%-)5(!1*)-(3!%4)#+3!5+*),%')!71%#)5)#)-)Z!

%#(*+&&)%3!#%1&+%3!$*1*)'(3!$+*)-%*5)'+3!$(/)#+1*($%')%3!+#-+0%/($%')%!$)%&'*)#($%')%!

S%#(,"2'$*')(*3$-,'*$L)/(#"C$%'-.(! ;$*0(&1(*2()

`)512)(#+!-%/-)'*)(/(! !"$(-%/-+4)%3!(&'+(5)&'*(0)%!!!

`)512)(#+!+*)'*($()+')#%! M#+4)%!

M14+#'(!*+#)#%3!aV<W! "$+*'+#&)(#+3!*)'+#2)(#+!5)!&(5)(3!&-(4$+#&(!-%*5)%-(!

! !

!

!

!

!

Page 97: sbobinature nefro_0 - SkyDrive

S%#(,"2'$*()3(%%5(a1'%'C,'$)'3,$(%(##,$%'#'-$)(3)"-'3$LC"0()!

;$*0(&1(*2())

<!M-:1%! <!`)'+#2)(#+!)5*)-%3!)$(#%'*+4)%!

<!O(5)(! <!!a&$%#&)(#+!5+//%!,(/+4)%!+!5+/!-(4$%*')4+#'(!)#'+*&')2)%/+3!)$+*'+#&)(#+3!+5+4)3!&-(4$+#&(!-%*5)%-(!

<!!H('%&&)(! <!"$+*]%/)+4)%!

<!q)-%*6(#%'(! <!M-)5(&)!4+'%6(/)-%3!(&'+(5)&'*(0)%!

<!X%7#+&)(! <!"$+*4%7#+&)+4)%3!(&'+(5)&'*(0)%!

<!k(&0%'(!!

<!"$+*0(&0%'+4)%3!(&'+(5)&'*(0)%!!

!

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

E+!&-(*)+!%2('%'+!&(#(!-/%&&)0)-%'+!&1//%!6%&+!3(%%()%$,$)-","##(,'0#'-.()3')(%'/'*"2'$*()-$*)%()/(#$3'-.()3'"%'#'-.(Q)

< !'--$%()/$%(-$%()(%'/'*"#()-$*)%5(/$3'"%'0')#,"3'2'$*"%(3!6%&%'%!&1//%!5)001&)(#+!&+4$/)-+8!

< O(3'()/$%(-$%()Y$+&(!)#0+*)(*+!%//B%/614)#%Z!(%'/'*"C'%')#,"/'#()/(/C,"*()"3)"%#")(++'-'(*2"8!

< O$%(-$%()*$*)3'"%'22"C'%'3!-)(?!4(/+-(/+!-.+!)#5)$+#5+#'+4+#'+!5%/!/(*(!$+&(!4(/+-(/%*+!&(#(!/+7%'+!%//+!$*('+)#+!$/%&4%')-.+8!H+*!0(*'1#%3!7/)!1*+4)-)!#(#!&16)&-(#(!-(#&+71+#2+!$%*')-(/%*4+#'+!%77*+&&),+!5%!:1+&'+!

Page 98: sbobinature nefro_0 - SkyDrive

4(/+-(/+8!T#!+&+4$)(!?!*%$$*+&+#'%'(!5%)!0%*4%-)3!'%#'B?!-.+!)#!'(&&)-(/(7)%3!$+*!+/)4)#%*+!:1+&')!&(/1')3!&)!*)-(**+!%//%!$/%&4%0+*+&)3!+!#(#!%//%!5)%/)&)8!

!

E%!&)#5*(4+!1*+4)-%!?!-%*%''+*)22%'%!5%!1#%!&+*)+!5)!5)&'1*6)!-.+!$(&&(#(!+&&+*+!-/%&&)0)-%')!&1//%!6%&+!5+/!-()#,(/7)4+#'(!5B(*7%#(!(!5+//%!7*%,)'>!5+)!&)#'(4)8!^/)!%$$%*%')!-()#,(/')!!+5!)!$*)#-)$%/)!5)&'1*6)!&(#(G!

< S66","#$)&"0#,$'*#(0#'*"%()L1)!/B"*$,(00'"!?!)/!&+7#(!$*)#-)$%/+C!*"10(")()7$/'#$!Y%#-.+!)#-(+*-)6)/+Z!&(#(!)!&)#'(4)!7*%,)!/+7%')!%//B%$$%*%'(!^"8!H(&&(#(!+&)&'+*+!%#-.+!%/'+*%2)(#)!5+/!'*%#&)'(!)#'+&')#%/+!+!5)%**+%8!!

!

< <'0#(/")*(,7$0$)-(*#,"%()O(#(!)#'+*+&&%'+!/%!0+(,")"++(##'7"!+!/%!0+(,")-$&*'#'7"9)O)!,%!5%!&)#'(4)!*+/%'),%4+#'+!/)+,)!Y)#&(##)%3!5+$*+&&)(#+3!+10(*)%3!$+*5)'%!5+//B%''+#2)(#+Z!%!-(#5)2)(#)!$)F!&+*)+3!-(4+!5)&'1*6)!-(7#)'),)3!5)&'1*6)!5+//(!&'%'(!5)!-(&-)+#2%3!-(#,1/&)(#)3!0)#(!%/!-(4%8!d!$+*!:1+&'(!-.+!)/!$%2)+#'+!41(*+8!

!

< !$%'*(1,$6"#'"))aB!&)%!5)!')$(!&+#&)'),(!Y7%46+!1*+#')Z!-.+!4('(*)(!Y&)#5*(4+!5+//%!7%46%!&+#2%!*)$(&(Z8!

< O$*$*(1,$6"#'")0(*0'#'7")V)$)-(!5)&'1*6(!1*+4)-(!4%/!-(#'*(//%6)/+8!

< !,1,'#$)M/'*(!5)&'1*6(!4%/!-(#'*(//%6)/+8!`)&$(#5+!&(/(!%7/)!%#')$&)-(')-)8!!!

< S%#,')3'0#1,C')*$*)'*a1"3,"C'%')V+#5(#(!%!*)4%#+*+!$(-(!-(#'*(//%6)/)!%#-.+!#+/!$%2)+#'+!5)%/)22%'(8!!

< !(,'-",3'#()E%!$+*)-%*5)'+!1*+4)-%!?!%5+&&(!1#%!4%#)0+&'%2)(#+!*%*%C!#(#!.%!/+!')$)-.+!%/'+*%2)(#)!a\^!5+//%!$+*)-%*5)'+3!4%!&)!-(4$(*'%!-(4+!1#%!$+*)-%*5)'+!

Page 99: sbobinature nefro_0 - SkyDrive

+&&15%'),%G!+&)&'+!)/!*)&-.(!5)!'%4$(#%4+#'(!-%*5)%-(3!+!5%/!$1#'(!5)!,)&'%!&+4+)(/(7)-(!?!%#%/(7%8!E%!'+*%$)%!5)%/)')-%!/%!*)&(/,+8!

E)+,)! X(5+*%')! O+,+*)!

M#(*+&&)%!b%1&+%!!"#&(##)%!"**+:1)+'+22%!`)512)(#+!5+//%!!-%$%-)'>!5)!%''+#2)(#+3!5+//B)5+%2)(#+!+!5+//%!/)6)5(!!!!

h(4)'(!M&'+#)%!k%')-%6)/)'>!O(##(/+#2%!"#,+*&)(#+!*)'4(!&(##(<,+7/)%!"#&'%6)/)'>!+4('),%!_)&'1*6)!$%*%#()-)!`)512)(#+!5+//+!01#2)(#)!-(7#)'),+!_)&'1*6)!&+&&1%/)!!

H*1*)'(!b+1*($%')%!$+*)0+*)-%!_)&(*)+#'%4+#'(!\(#01&)(#+!4+#'%/+!_)&'1*6)!-(4$(*'%4+#<'%/)!+!5+/!/)#71%77)(!"$('+*4)%!X)(-/(#(!M&'+*)g)&!\(#,1/&)(#)!O'1$(*+!\(4%!

X%/#1'*)2)(#+!-%/(*)-(<$*('+)-%!!

!

_")-$/6",0")3(')0'*#$/')1,(/'-')'/6%'-")%")*(-(00'#:)3')'*'2'",()%")#(,"6'")0$0#'#1#'7"9)a&&%!$1N!+&&+*+!+00+''1%'%!)#!51+!4(5)G!

< V*%$)%#'(!5)!*+#+!< V+*%$)%!5)%/)')-%!

!

8(,"6'")3'"%'#'-")

E%!5)%/)&)!$1N!+&&+*+!+g'*%-(*$(*+%!(!$+*)'(#+%/+3!+!:1+&'B1/')4%!&)!6%&%!&1!1#!$*)#-)$)(!-(4$/+'%4+#'+!5),+*&(!*)&$+''(!%//%!5)%/)&)!+g'*%-(*$(*+%8!b+//%!5)%/)&)!$+*)'(#+%/+3!,)+#+!4+&&%!#+/!$+*)'(#+(!1#%!&(/12)(#+!)$+*(&4(')-%!Y&$+&&(!%!6%&+!5)!5+&'*)#+ZG!:1+&'(!/):1)5(!%'')*%!%-:1%3!&(5)(!+!&(/1')!%''*%,+*&(!/%!4+46*%#%!$+*)'(#+%/+3!-(#!4+--%#)&4(!$1*%4+#'+!(&4(')-(3!&(4)7/)%#'+!$+*!-+*')!%&$+'')!%)!4+--%#)&4)!5)!')$(!-(#,+''),(8!L1+&'%!4+'(5)-%!$+*4+''+!&-%46)!/)4)'%')3!4%!?!1#%!4+'(5)-%!0(/'-$*#'*1"!-.+!01#2)(#%!$+*0+''%4+#'+!)#!&(77+'')!-(#!$+*)'(#+(!)5(#+(8!E+!5)%/)&)!$+*)'(#+%/+!&)!$1N!0%*+!)#!51+!4(5)G!

< X+'(5)-%!%1'(4%')22%'%G!)/!$%2)+#'+!&)!-(//+7%!51*%#'+!/%!#(''+!%5!1#%!4%--.)#%!-.+3!(7#)!51+!(!'*+!(*+3!7/)!%&$)*%!)/!/):1)5(!@1&%'(A!5%/!$+*)'(#+(!+!/(!&(&')'1)&-+!-(#!:1+//(!#1(,(8!!

< X+'(5)-%!4%#1%/+G!)/!$%2)+#'+!?!41#)'(!5)!&%--.+!+!%/!4(4+#'(!($$(*'1#(!+&+71+!4%#1%/4+#'+!/%!&(&')'12)(#+!5+/!/):1)5(8!!

9*4%)!:1%&)!'1'')!1')/)22%#(!/+!4+'(5)-.+!%1'(4%')22%'+G!&(#(!$%*')-(/%*4+#'+!61(#+3!&$+-)%/4+#'+!$+*!)!6%46)#)3!)#!:1%#'(!)#0)#)'%4+#'+!4+#(!'*%14%')-.+8!_%!#()!&(#(!$(-(!1&%'+!$+*!4('),)!+-(#(4)-)!Y-(&'%#(!'*($$(!$(-(!$+*!)!0(*#)'(*)Z8!"/!$*(6/+4%!?!-.+!%/-1#+!$+*&(#+!#(#!&(#(!)5(#++!%!:1+&'%!4+'(5)-%!%!-%1&%!5)!-%*%''+*)&')-.+!5+/!$+*)'(#+(8!"#!%/-1#+!$+*&(#+3!$()3!&)!,+*)0)-%!1#%!)**)'%2)(#+!5+//%!4+46*%#%!$+*)'(#+%/+3!

Page 100: sbobinature nefro_0 - SkyDrive

$+*!-1)!5($(!1#!-+*'(!$+*)(5(!5)!'+4$(!+&&%!#(#!?!$)F!)#!7*%5(!5)!-(#&+#')*+!1#%!5)%/)&)!%5+71%'%8!

E%!5)%/)&)!+g'*%-(*$(*+%!&)!6%&%!&1!51+!$*)#-)$)G!

>9 !,'*-'6'$)3'++10'7$)

"/!&)&'+4%!$*+,+5+G!

< X+46*%#%!&+4)$+*4+%6)/+3!-.+!0(*4%!)/!0)/'*(!< \)*-1)'(!$+*!)/!&%#71+!< E):1)5(!1/'*%$1*(!!< O(&'%#2+!,%*)+!+5!+/+''*(/)')!5%!%77)1#7+*+!%/!/):1)5(!1/'*%$1*(!$+*!(''+#+*+!

/%!-(#-+#'*%2)(#+!5+&)5+*%'%8!

EB(6)+''),(!?!:1+//(!5)!(''+#+*+!1#(!0-"/C'$)6(,)3'++10'$*(8!H+*'%#'(3!&)--(4+!,(7/)%4(!+/)4)#%*+!&-(*)+!%2('%'+3!#(#!#+!4+'')%4(!#+/!/):1)5(!5)%/)')-(3!)#!4(5(!'%/+!-.+!+&&+!5)00(#5%#(!5%/!$/%&4%!5+/!$%2)+#'+!%/!/):1)5(!5)%/)')-(8!!

H+*!:1%#'(!*)71%*5%!)/!&(5)(3!#(#!/(!,(7/)%4(!4(5)0)-%*+G!$+*'%#'(3!)/!/):1)5(!5)%/)')-(!%,*>!/%!&'+&&%!-(#-+#'*%2)(#+!)#!&(5)(!5+/!&%#71+!5+/!$%2)+#'+8!

^/)!%4)#(%-)5)!'+#5(#(!%5!+&&+*+!$+*&)!51*%#'+!)/!$*(-+&&(!5)%/)')-(G!$+*!:1+&'(!$*+&-*),+*+4(!%/!$%2)+#'+!1#%!5)+'%!'6(,6,$#('-")31,"*#()%")+"0()3'"%'#'-"9)O'+&&(!5)&-(*&(!$+*!/+!,)'%4)#+8!

H+*!:1%#'(!*)71%*5%!*)71%*5%!)/!-%/-)(3!)#!/)#+%!5)!4%&&)4%!/(!,(7/)%4(!*+)#'+7*%*+3!$+*'%#'(!/(!4+''+*+4(!%!-(#-+#'*%2)(#+!$)F!+/+,%'%!#+/!/):1)5(!5)%/)')-(8!

H+*!:1%#'(!*)71%*5%!)/!$('%&&)(3!/(!,(7/)%4(!*)51**+!4%!#(#!'*($$(G!$+*'%#'(!1')/)22+*+4(!1#%!-(#-+#'*%2)(#+!%5+71%'%!$+*!0%,(*)*+!1#%!-+*'%!:1('%!5)!5)001&)(#+!5+/!$('%&&)(!,+*&(!)/!/):1)5(!5)%/)')-(8!

H+*!:1%#'(!*)71%*5%!)/!6)-%*6(#%'(3!/(!,(7/)%4(!0(*#)*+!%/!$%2)+#'+G!/(!4+''+*+4(!:1)#5)!%!-(#-+#'*%2)(#+!$)F!+/+,%'%!#+/!/):1)5(!5)%/)')-(8!

EB1#)-%!-(&%!-.+!*$*)6$00'"/$)6$,#",()7'")-(#!:1+&'%!4+'(5)-%!?!/%!4%&&%!5)!/):1)5(!%--141/%'(!'*%!1#%!&+51'%!+!/B%/'*%8!L1+&'(!$%*%4+'*(!,)+#+!-(**+''(!*+7(/%#5(!)/!$*(-+&&(!5)!1/'*%0)/'*%2)(#+8!H*)4%!5)!)#)2%*+!/%!5)%/)&)!)/!$%2)+#'+!,)+#+!$+&%'(G!&+!*)&1/'%!+&&+*+!)#!&(,*%$$+&(!Y4%7%*)!%#-.+!)$+*'+&(3!+5+4%'(&(Z3!&)7#)0)-%!-.+!5%//B1/')4%!&+51'%!5)%/)')-%!#(#!-B?!&'%'(!1#!-(**+''(!6)/%#-)%4+#'(!'*%!$+*5)'+!5)!/):1)5)!+5!)#'*()')!5)!/):1)5)8!H+*'%#'(3!&)!*+7(/%!)/!4%--.)#%*)(!$+*!0%*!&e!-.+!)/!$%2)+#'+!$+*5%!'*%4)'+!/B1/'*%0)/'*%2)(#+!/%!:1%#')'>!5)!%-:1%!+!&(5)(!)#!+--+&&(8!

!

A9 !,'*-'6'$)-$*7(##'7$)

"/!&%#71+!5+/!$%2)+#'+!,)+#+!&$)#'(!-(#!1#%!-+*'%!$*+&&)(#+!Y#+7%'),%Z!-(#'*(!1#%!4+46*%#%!&+4)$+*4+%6)/+8!EB%-:1%!$%&&%!7*%2)+!%//%!$*+&&)(#+!+!)!&(/1')!5)&-)(/')!&+71(#(!$+*!'*%&-)#%4+#'(8!H+*!0%*+!1#%!+4(0)/'*%2)(#+!$1*%3!$+*N3!5+,(!$(*'%*+!,)%!IS<KP!/)'*)!5)!%-:1%3!,%/+!%!5)*+!4+'>!5+/!$+&(!-(*$(*+(8!H+*'%#'(3!5(,*N!*+)#'+7*%*+!1#B)5(#+%!:1%#')'>!5)!&(/12)(#+!%$$(&)'%4+#'+!$*+$%*%'%!+!'%*%'%8!!

_)!&(/)'(!&)!1')/)22%!1#%!/(#$3'-")/'0#"Q)(/$3'"+'%#,"2'$*(9!a&&%!&0*1''%!&)%!)/!4+--%#)&4(!-(#,+''),(!-.+!:1+//(!+4(0)/'*%'),(3!-(&)--.[!,)!&)%#(!%#-.+!&-%46)!5)001&),)!'*%!&(&'%#2+!%!5),+*&+!-(#-+#'*%2)(#)8!M#-.+!)#!:1+&'(!-%&(!%66)%4(!1#%!$+*5)'%!#+''%!

Page 101: sbobinature nefro_0 - SkyDrive

5)!/):1)5)!YQP<SP!/)'*)Z!-.+!%#5*%##(!*+)#01&)!&1/!-)*-1)'(!D!%!&+-(#5%!5)!5(,+!*+)#0(#5)%4(3!$*)4%!5+//%!4+46*%#%!(!5($(!/%!4+46*%#%!<!!%,*+4(!+00+'')!0%,(*+,(/)!&1//%!-(#-+#'*%2)(#+!5+)!&(/1')!5+/!$%2)+#'+!Y+&G!5)/1)2)(#+!$*('+)#+3!&(&'%#2+!-.+!%14+#'%#(!/%!,)&-(&)'>Z!+!:1)#5)!0%,(*)%4(!&)%!)/!4+--%#)&4(!-(#,+''),(!-.+!)/!4+--%#)&4(!5)001&),(8!!

"#!(7#)!-%&(3!$+*!0%*+!/%!5)%/)&)3!&+*,(#(!4+46*%#+!-(#!5+'+*4)#%'+!-%*%''+*)&')-.+8!E%!4+46*%#%!$+*!)/!4+'(5(!-(#,+''),(!?!1#%!4+46*%#%!"3)"%#")(++'-'(*2"G!(,,+*(3!-(#!61-.)!$)F!/%*7.)!+!5+$1*%#(!4(/'(!4+7/)(!/+!4(/+-(/+!5)!7*%#5)!5)4+#&)(#)8!H+*!+&+4$)(3!5%!:1%#5(!&)!1&%#(!/+!4+'(5)-.+!-(#,+''),+!#(#!&)!,+5+!$)F!/B%4)/()5(&)!5%!%--141/(!5)!!I<4)-*(7/(61/)#%8!!

O+*,+!$()!1#!5)%/)22%'(!YWIP<WKP!EZ3!$*+$%*%'(!-(#!1#!)4$)%#'(!5)!5+$1*%2)(#+!4(/'(!&(0)&')-%'(!)#!7*%5(!5)!$*(51**+!%-:1%!1/'*%$1*%8!M66)%4(!$()!6)&(7#(!5+//+!&%--.+!5)!-(#-+#'*%')8!!

"#0)#+3!%66)%4(!6)&(7#(!5)!1#!"--(00$)7"0-$%",(9)"/!$%2)+#'+!5+,+!%,+*+!1#%!,+#%!&1$+*0)-)%/+!5)!7*(&&(!-%/)6*(!-(#!+/+,%'(!0/1&&(!-.+!$+*4+''%!5)!4%#'+#+*+!)/!*+7)4+!5+/!-)*-1)'(!YKPP<KSP!4/U4)#Z!)#!1&-)'%!+!)#!+#'*%'%8!M!:1+&'(!&-($(3!/%!0)&'(/%!4)7/)(*+!?!:1+//%!#%'),%3!-)(?!:1+//%!*+%/)22%'%!%#%&'(4)22%#5(!1#B%*'+*)%!5+/!6*%--)(!-(#!1#%!,+#%!5+/!6*%--)(8!E%!0)&'(/%!5+,+!+&&+*+!/%!$)F!5)&'%/+!$(&&)6)/+8!a&)&'+!%#-.+!/%!$(&&)6)/)'>!5)!1&%*+!-%'+'+*)!$%*')-(/%*)!$(&)2)(#%')!#+)!,%&)!5+/!-(//(G!&)!1&%#(!:1%#5(!)/!$%2)+#'+!#(#!.%!$)F!,+#+!5)&$(#)6)/)!&1/!6*%--)(!(!51*%#'+!)/!'+4$(!5)!4%'1*%2)(#+!5)!1#%!0)&'(/%!%*'+*(,+#(&%!#%'),%!YK<;!4+&)Z8!!

_1*%#'+!/%!5)%/)&)!$(&&(#(!,+*)0)-%*&)!1#%!&+*)+!5)!$*(6/+4)3!-(4+!$1*+!51*%#'+!/%!,)'%!:1(')5)%#%!5+/!5)%/)22%'(8!"#!$%*'+3!/%!-(#')#1%2)(#+!5+//+!-(4$/)-%#2+!-%*5)(,%&-(/%*)3!+4%'(/(7)-.+3!)#0+''),+!-.+!-%*%''+*)22%#(!)/!$%2)+#'+!5)%/)22%'(C!)#!$%*'+!&)!'*%''%!5)!-$/6%'-"*2()"-1#()3(%)6"2'(*#()3'"%'22"#$Q)

< R6(,W"%'(/'")< 43(/")6$%/$*",()"-1#$)

a#'*%46+!:1+&'+!-(4$/)-%2)(#)!&)!,+*)0)-%#(!'%#'(!$)F!0%-)/4+#'+!:1%#5(!)/!$%2)+#'+!#(#!&+71+!-(#!$*+-)&)(#+!/+!*+7(/+!-.+!7/)!&(#(!)4$(&'+3!&($*%''1''(!*)71%*5(!%//B)#'*()'(!5)!/):1)5)8!b(#!%$$+#%!/%!5)%/)&)!'+*4)#%3!%/-1#)!&(/1')!)#'*%-+//1/%*)!-(4)#-)%#(!)44+5)%'%4+#'+!%!$%&&%*+!#+/!$/%&4%!5+$1*%'(3!:1)#5)!-(#!-(#-+#'*%2)(#+!5+)!4+5+&)4)!&(/1')!$)F!6%&&+8!L1+&'(!&$)+7%!/%!5)00+*+#2%!'*%!/+!4)&1*%2)(#)!5+//%!|1*+%}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

O)!$%*/%!%//(*%!5)!"3(&1"#(22")3'"%'#'-"!-(#&)5+*%#5(!:1%/)!&)%#(!)!#(&'*)!,%/(*)!5%!*%77)1#7+*+!%/!'+*4)#+!5+//%!&+51'%!5)%/)')-%!$+*!0%*+!)#!4(5(!-.+!/B%--141/(!-.+!&)!,+*)0)-%!#+/!$+*)(5(!)#'+*5)%/)')-(!$+*4+''%!5)!*%77)1#7+*+!/),+//)!-(4$%')6)/)!-(#!1#%!61(#%!:1%/)'>!5)!,)'%8!O)!*)')+#+!-.+!1#%!5)%/)&)!&)%!%5+71%'%!:1%#5(!/%!-(#-+#'*%2)(#+!5+//B1*+%!&)!*)51-+!%/!A@s)3(')7"%$,')*$,/"%'9)_5"3(&1"#(22")3'"%'#'-")7'(*()-$*#,$%%"#")1*")7$%#")"%%")0(##'/"*"9))

)

Page 102: sbobinature nefro_0 - SkyDrive

\(4$/)-%#2+!5+//B)#&100)-)+#2%!*+#%/+!

\(#!)/!$*(7*+&&),(!5+-/)#(!5+//%!01#2)(#+!*+#%/+3!)#)2)%#(!%!-(4$%*)*+!&+7#)!+!&)#'(4)!-.+!&(#(!5+0)#)')!-(4+!-$/6%'-"*2()3(%%5'*01++'-'(*2"),(*"%(9!L1+&'+!-(#5)2)(#)!,+#7(#(!-(&e!5+0)#)'+!$()-.[3!%#-.+!&+!#+/!-(4$/+&&(!&(#(!%66%&'%#2%!-%*%''+*)&')-.+3!-)%&-1#%!5)!+&&+!.%!1#%!-+*'%!%1'(#(4)%!+!-%*%''+*)&')-.+!-/)#)-.+!$+-1/)%*)8!E+!-(#5)2)(#)!-.+!*%$$*+&+#'%#(!/+!-(4$/)-%#2+!5+//B"`!$(&&(#(!$*+&+#'%*&)!%#-.+!)#!-(*&(!5)!%/'*+!4%/%'')+3!+!)#!'%/!-%&(!,%!$(&'%!5)%7#(&)!5)00+*+#2)%/+8!EB1/'+*)(*+!$*(7*+&&),%!$+*5)'%!5+//%!01#2)(#+!*+#%/+!&)!4%#)0+&'%!-(#!)/!:1%5*(!5+//%!1,(/'")#(,/'*"%(3!5)!-1)!%66)%4(!7)>!$%*/%'(8!!

E+!-(4$/)-%#2+!5+//B)#&100)-)+#2%!*+#%/+!-*(#)-%!&(#(!/+7%'+!%!'*+!(*5)#)!5)!0+#(4+#)G!

>9 V(+'-'#)3')(%'/'*"2'$*()3(')6,$3$##')"2$#"#')M#-.+!&+!)/!$%2)+#'+!#(#!?!1*+4)-(3!&)!,+*)0)-%!-(41#:1+!1#!-+*'(!7*%5(!5)!*)'+#2)(#+!5)!$*(5('')!%2('%')8!!

A9 U'312'$*()3(%%")-"6"-'#:)3'),(&$%"2'$*()3(%%5(a1'%'C,'$)'3,$(%(##,$%'#'-$)

)

D9 R*01++'-'(*2")(*3$-,'*")3(%),(*()

)

^*(&&(/%#%4+#'+3!'1''+!:1+&'+!-(4$/)-%#2+!)#)2)%#(!%!,+*)0)-%*&)!:1%#5(!)/!$%2)+#'+!+#'*%!)#!&'%5)(!5)!'*01++'-'(*2"),(*"%()/$3(,"#")I<#"3'$)RRRQ)`^U)#,")D@)()Z@)/%E/'*J9)"#!*+%/'>3!:1+&'(!?!1#!/1#7(!$+*)(5(!5+//%!,)'%!5+/!4%/%'(3!'%#'B?!-.+!?!&'%'(!$*($(&'(!5)!5),)5+*+!/(!&'%5)(!"""!)#!51+!&(''(&'%5)8!

M#+4)%!

EB"*(/'")7+#+*%/4+#'+!&)!,+*)0)-%!#+)!$%2)+#')!-(#!)#&100)-)+#2%!*+#%/+!4(5+*%'%3!-(#!0)/'*%'(!7/(4+*1/%*+!$%*)3!7*(&&(/%#%4+#'+3!%!QP!4/U4)#8!EB%#+4)%!?!5+0)#)'%!-(4+!*)512)(#+!5+//B+4(7/(6)#%!%/!5)!&(''(!5+/!iS+&)4(!$+*-+#')/+!5+//%!$($(/%2)(#+!#(*4%/+8!b+//%!&)'1%2)(#+!5+)!H%+&)!(--)5+#'%/)3!)/!,%/(*+!&(7/)%!?!5)!WK3S!7U5/!$+*!/B1(4(!+!WI!7U5/!$+*!/+!5(##+8!EB%#+4)%!5+//%!4%/%'')%!*+#%/+!-*(#)-%!?!)#0/1+#2%'%!5%//%!4%/%'')%!5)!6%&+G!5(66)%4(!'+#+*+!$*+&+#'+!-.+!/+!-+//1/+!&+-+*#+#')!aH9!&)!'*(,%#(!#+//%!4)5(//%*+!5+/!*+#+3!$%*')-(/%*4+#'+!#+//%!$(*2)(#+!$*(0(#5%!5+//%!4)5(//%*+8!H+*'%#'(3!$%2)+#')!-(#!4%/%'')+!'161/()#'+*&')2)%/)!'+#5+*%##(!%!&,)/1$$%*+!/B%#+4)%!$)F!$*+-(-+4+#'+!Y%#-.+!-(#!1#!0)/'*%'(!7/(4+*1/%*+!)#'(*#(!%)!;P!4/U4)#ZC!$%2)+#')!-(#!4%/%'')%!7/(4+*1/%*+3!/B%#+4)%!'+#5+!)#,+-+!%!-(4$%*)*+!:1%#5(!)/!^k`!?!-)*-%!YQP!4/U4)#ZC!-)!&(#(!$()!$%2)+#')!D!+&G!*+#+!$(/)&')-(!D!)#!-1)!&)!.%!1#%!-+*'%!$*(512)(#+!5)!aH9!5%!$%*'+!5)!-+//1/+!-.+!7+#+*%/4+#'+!#(#!/%!$*(51**+66+*(3!+!)#!'%/!-%&(!&)!%,*>!1#B%#+4)%!4+#(!7*%,+!+!%5!)#&(*7+#%!4(/'(!'%*5),%3!(!%55)*)''1*%!#(#!&)!%,*>!%#+4)%8!

9/'*+!%//%!-%*+#2%!5)!aH93!,)!&(#(!%/'*)!0%''(*)!-()#,(/')!#+//B%#+4)%G!

< `)512)(#+!5+//%!,)'%!4+5)%!+*)'*(-)'%*)%!< "/!$%2)+#'+!)#!5)%/)&)!'+#5+!%5!%,+*+!1#!5+0)-)'!5)!0(/%')!< "/!$%2)+#'+!1*+4)-(!$1N!%,+*+!1#B%#+4)%!)$(*)7+#+*%'),%!5%!'(&&)-)'>!

4)5(//%*+!5)*+''%!

"/!5+0)-)'!5)!aH9!0%!&e!-.+!/%!0)/)+*%!+*)'*()5+!5),+#')!4+#(!*%$$*+&+#'%'%!+!-.+!)!$*+-1*&(*)!+*)'*()5)!&($*%,,),%#(!4+#(!0%-)/4+#'+!#+/!-(#'+&'(!5+//%!#)--.)%!+4%'($()+')-%G!-B?!

Page 103: sbobinature nefro_0 - SkyDrive

:1)#5)!1#%!&(*'%!5)!)$($/%&)%!+*)'*()5+8!O)!'*%''%!:1)#5)!5)!1#B%#+4)%!)$(*)7+#+*%'),%3!-.+!&)!$*+&+#'+*>!-(#G!

< a4%'(-*)'(!6%&&(!< a4(7/(6)#%!6%&&%!< ;$*#"),(#'-$%$-'#",'")C"00"!< X\h!7+#+*%/4+#'+!#(*4%/+!< X\l\!7+#+*%/4+#'+!#(*4%/+!< M$'(7/(6)#%!#(*4%/+!< E_l!#(*4%/+!< X+'%6(/)&4(!4%*2)%/+!-(#&+*,%'(!

"/!6"2'(*#()'*)3'"%'0'3!)#,+-+3!.%!1#!-(4$(*'%4+#'(!$%*')-(/%*+!5+/!&1(!4+'%6(/)&4(!4%*2)%/+G!$*+&+#'%#(!1#B%/'+*%2)(#+!5%!-(#5)2)(#+!-*(#)-%!-(#!&)5+*+4)%!#(*4%/+!(!*)5(''%3!0+**)')#+4)%!+/+,%'%!+!'*%#&0+**)#+4)%!6%&&%!+!-(#!&%'1*%2)(#+!5+//%!'*%#&0+**)#%!#+//%!#(*4%8!L1)#5)3!:1%#5(!#()!&(44)#)&'*)%4(!aH9!#+/!$%2)+#'+!5)%/)22%'(3!5(66)%4(!-(#'+4$(*%#+%4+#'+!&(44)#)&'*%*+!+(,,$)'*)+$,/")'//(3'"#"/(*#()3'06$*'C'%()6(,)7'")(*3$7(*$0"9)!

EB%#+4)%!&)5+*($+#)-%!*$*)i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a`M!&)!$1N!&(44)#)&'*%*+!%#-.+!$+*!,)%!&(''(-1'%#+%3!%!5)00+*+#2%!5+//%!,+--.)%!aH93!-.+!&+!&(44)#)&'*%'%!&(''(-1'+!$('+,%!5%*!/1(7(!%//%!0(*4%2)(#+!5)!%#')-(*$)!+!-(#&+71+#'+!%#+4)%!%$/%&')-%8!"/!$%2)+#'+!7+#+*%/4+#'+!&)!&(44)#)&'*%!SPPP<WP8PPP!1#)'>!D!)#)2)%/4+#'+!1#%!,(/'%!%//%!&+'')4%#%3!$+*!$()!&-%/%*+!/%!0*+:1+#2%!5)!&(44)#)&'*%2)(#+!Y1#%!&(44)#)&'*%2)(#+!4+#&)/+!5),+#'%!)#!7+#+*+!&100)-)+#'+Z8!!

"/!,%/(*+!5)!+4(7/(6)#%!3(0'3(,"C'%(!$+*!:1+&')!$%2)+#')!?!WW<WI!7U5/8!L1+&'(3!$+*-.[!-(**+2)(#)!4)7/)(*)!.%##(!1#!-+*'(!+00+''(!6+#+0)-(!&1//%!:1%/)'>!5+//%!,)'%!D!-(41#:1+!#(#!+&%7+*%'(!D!4%!."**$)(++(##')-$%%"#(,"%')'/6$,#"*#'Q)

< S1/(*#$)3(%),'0-.'$)3')'*-'3(*#')-(,(C,$7"0-$%",')< S1/(*#$)3(%),'0-.'$)3')3'"%'0')'*"3(&1"#"!$+*!'*(46(&)!51*%#'+!/%!

$*(-+51*%!5)%/)')-%!+!'*(46(&)!5+//%!0)&'(/%!%*'+*(,+#(&%8!)< S1/(*#$)3(%),'0-.'$);j)

)

)"$+*]%/)+4)%!

"/!$('%&&)(!.%!1#%!-(#-+#'*%2)(#+!$/%&4%')-%!5)!K3S<S!4a:UE8!T#!$%2)+#'+!-(#!01#2)(#+!*+#%/+!#(*4%/+!0)/'*%!IW8PPP!4a:!5)!&(5)(!+!WSPP!4a:!5)!$('%&&)(8!H+*!4%#'+#+*+!/B(4+(&'%&)3!%!&+-(#5%!5)!:1+//(!-.+!4%#7)%3!5+,+!+/)4)#%*+!5%!SP!%!KPP!4a:!5)!&(5)(!+!7*(&&(4(5(!SP<WPP!4a:!5)!$('%&&)(8!"/!-%*)-(!0)/'*%'(!?!5%!WP!%!WPP!,(/'+!4%77)(*+G!

Page 104: sbobinature nefro_0 - SkyDrive

*)%&&(*6+#5(#+!/BWR!)/!7)(-(!?!0%''(8!b+/!$%2)+#'+!-(#!"`!%,%#2%'%!/%!&)'1%2)(#+!?!4(/'(!5),+*&%G!$+*!:1%#'(!*)71%*5%!)/!&(5)(3!#+!,+#7(#(!0)/'*%')!-)*-%!IPPP!4a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

"/!$*(6/+4%!5+/!$('%&&)(!?!6+#!5),+*&(G!)/!$%2)+#'+!-(#!)#&100)-)+#2%!*+#%/+!+!^k`!5)!S!4/U4)#!Y$+*!0%*+!1#!+&+4$)(!&)7#)0)-%'),(Z!.%!1#!0)/'*%'(!5)!$('%&&)(!4(/'(!*)5(''(3!!,)-)#(!%)!=P!4a:U5)+3!(,,+*(!/%!:1('%!5)!$('%&&)(!-.+!5+,+!+&&+*+!+/)4)#%'%!7)(*#%/4+#'+!$+*!4%#'+#+*+!/B(4+(&'%&)3!:1)#5)!5(,*+66+!+/)4)#%*+!$*%')-%4+#'+!'1''(!)/!$('%&&)(!-.+!0)/'*%!$*!4%#'+#+*+!/B(4+(&'%&)G!)/!$*(6/+4%3!:1)#5)3!?!-.+!%#-.+!)/!4)#)4(!*)%&&(*6)4+#'(!5)!$('%&&)(!$1N!5+'+*4)#%*+!1#!%14+#'(!5+//%!$('%&&)+4)%{!"/!$%2)+#'+!)#!5)%/)&)3!$()3!#(#!0)/'*%!)/!$('%&&)(G!'1''(!)/!$('%&&)(!%&&1#'(!,)+#+!%--141/%'(!+!5+,+!+&&+*+!+/)4)#%'(!%''*%,+*&(!/%!$*(-+51*%!5)%/)')-%8!L1)#5)3!/%!$('%&&)+4)%!'+#5+!$+*!0(*2%!5)!-(&+!%!&%/)*+G!#+/!$%2)+#'+!-(#!)#&100)-)+#2%!*+#%/+!%,%#2%'%!Y#(#!)#!5)%/)&)Z3!,%/(*)!5)!;!4a:UE!&(#(!%66%&'%#2%!6+#!'(//+*%6)/)8!!

EB)$+*]%/)+4)%!&,"7(!Ys=8S!4a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b"](c"%"#()uZ8!!

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

"/!$%2)+#'+!-(#!)#&100)-)+#2%!*+#%/+!$*+<'+*4)#%/+!&)!'*(,%!%/!/)4)'+!5+//%!-%$%-)'>!5)!*+7(/%2)(#+!5+//B(4+(&'%&)!5+/!$('%&&)(C!4%7%*)3!&+!?!)#!'+*%$)%!-(#!M\a<"!+!&%*'%#)!5%!/1#7(!'+4$(!?!%6)'1%'(!%//%!&+#&%2)(#+!5+//B)$+*]%/)+4)%!/)+,+C!)/!$*(6/+4%!?!-.+3!&+!)/!$%2)+#'+!%&&14+!0%*4%-)!5%!6%#-(!-(#'+#+#')!$('%&&)(3!(!%#')%/5(&'+*(#)-)3!)#)6)'(*)!5+/!&)&'+4%!*+#)#%<%#7)('+#&)#%<%/5(&'+*(#+3!kMbO3!(!&+!.%!1#!+4%'(4%3!(!1#!%''%--(!-(#,1/&),(!Y*%65(4)(/)&)Z3!&')$&)!7*%,+3!$1*!#(#!+&&+#5(!%#-(*%!)#!0%&+!'+*4)#%/+!5+//B"`!$1N!%,+*+!1#!+$)&(5)(!5)!)$+*]%/)+4)%!7*%,+8!!L1)#5)3!0()*(%)6"2'(*#()'*)3'"%'0')%5'6(,W"%'(/'")&,"7()i)-"10"#")3"%%5(--(00'7$)"66$,#$)3')6$#"00'$)$)3"%%")/"*-"#")"001*2'$*()3(%%(),(0'*(G)*(%)6"2'(*#()6,(#(,/'*"%()&(*(,"%/(*#()3(,'7")3")(6'0$3')6,(-'6'#"*#'9)

Page 105: sbobinature nefro_0 - SkyDrive

O+!)/!$%2)+#'+!&($*%,,),+!%//B+$)&(5)(!%-1'(3!%")#(,"6'")3(%%5'6(,W"%'(/'")&,"7()-$*0'0#()*(%%")3'"%'0'G!1#%!&+51'%!5)!IP!4)#1')!-(#!5)%/)&%'(!$*),(!5)!$('%&&)(!?!&100)-)+#'+8!!

E%!3'"&*$0'!5)!)$+*]%/)+4)%!&)!0%!-(#G!

< 4`S)< 4;`)

E+!%/'+*%2)(#)!a\^!&(#(!%&&(/1'%4+#'+!')$)-.+8!!

b+//B%''+&%!5+//%!5)%/)&)3!+&)&'(#(!5),+*&)!4(5)!$+*!-(#'*(//%*+!$*(,,)&(*)%4+#'+!/%!&)'1%2)(#+G!

< !,$7$-",()%$)06$0#"/(*#$)3(%)6$#"00'$)*(%)-$/6",#'/(*#$)'*#,"-(%%1%",()L1+&'(!&)!('')+#+!&(44)#)&'*%#5(!)#&1/)#%!Y(,,)%4+#'+!&(44)#)&'*%#5(!-(#'+4$(*%#+%4+#'+!%#-.+!7/1-(&)(Z!+!$*%')-%#5(!/B%/-%/)#)22%2)(#+!5+/!$l!+4%')-(8!

!

< <$//'*'0#,"2'$*()3')0#'/$%"*#')H+*!+&+4$)(G!#(*%5*+#%/)#%3!!I<%7(#)&')8!L1+&')!0%*4%-)!&')4(/%#(!)/!#(5(!5+/!&+#(3!:1)#5)!&)!($$(#7(#(!%//%!5+$*+&&)(#+!-%1&%'%!5%//B)$+*]%/)+4)%8!

!

94+(&'%&)!&(5)-%!

"/!$%2)+#'+!-(#!)#&100)-)+#2%!*+#%/+!'+*4)#%/+!Y^k`!m!PZ!%--141/%!$+*!0(*2%!5)!-(&+!'1''(!)/!&(5)(!-.+!%&&14+8!"/!&(5)(!)#!:1%#'(!'%/+!#(#!'+#5+!%!4(5)0)-%*+!4(/'(!/%!$*($*)%!-(#-+#'*%#2)(#+!#+/!&%#71+G!/%!4(5)0)-%2)(#+!5+//%!-(#-+#'*%2)(#+!5)$+#5+!$)1--.+%/'*(!5%/!*%$$(*'(!'*%!&(5)(!+!%-:1%8!T#!%14+#'(!5+//%!:1%#')'>!5)!&(5)(!$*(,(-%!1#(!&$(&'%4+#'(!5+//B%-:1%!5%/!-(4$%*')4+#'(!)#'*%-+//1/%*+!%!:1+//(!+g'*%-+//1/%*+3!+!&($*%''1''(!&')4(/%!)/!&+#&(!5)!&+'+3!-.+!$(*'%!%//B%&&1#2)(#+!5)!%-:1%!+!%//%!&+-*+2)(#+!5)!M_l!Y-.+3!#+/!$%2)+#'+!-(#!)!*+#)!01#2)(#%#')!-%1&%!1#!%14+#'(!5+/!*)%&&(*6)4+#'(!5)!%-:1%!%/!0)#+!5)!*)$*)&')#%*+!/B(&4(/%/)'>!$/%&4%')-%Z8!b+/!$%2)+#'+!)#!5)%/)&)3!/B)#'*()'(!)5*)-(!7)(*#%/)+*(!5+,+!+&&+*+!$%*)!%//+!$+*5)'+!5)!%-:1%!)#+,)'%6)/)!Y'*%&$)*%2)(#+3!$+*5)'%!-(#!)/!&15(*+3!&+-*+2)(#)!^"3!+--cZG!$+*'%#'(3!&)!5)-+!-.+!/%!:1%#')'>!5)!%-:1%!5%!%&&14+*+!7)(*#%/4+#'+!?!)#'(*#(!%5!W!E8!"/!$1#'(!-*1-)%/+3!$+*N3!?!-.+!*$*)0')61v)+",(),(0#,'2'$*()'3,'-")0()*$*)0')+")-$*#(/6$,"*("/(*#(),(0#,'2'$*()0$3'-"q!E%!*+&'*)2)(#+!5)!&(5)(!$*(,(-%!1#%!4)#(*+!&+-*+2)(#+!5)!M_l!+!:1)#5)!-(#'*(//%!/%!&+5+3!$()-.[!/B(&4(/%/)'>!$/%&4%')-%!&)!4%#')+#+!-(&'%#'+8!

b+/!$+*)(5(!)#'+*5)%/)')-(3!)/!$%2)+#'+!'+#5+!-(41#:1+!%5!%--141/%*+!%-:1%!+!&(5)(3!'%#'B?!,+*(!-.+!$*)4%!5)!(7#)!&+51'%!5)%/)')-%!+7/)!5+,+!+&&+*+!$+&%'(3!+5!)/!&1(!$+&(!,)+#+!-(#0*(#'%'(!-(#!)/!6(0$)0(--$)5+/!$%2)+#'+8!H()3!%''*%,+*&(!/%!*+7(/%2)(#+!5+/!$*(-+&&(!5)!1/'*%0)/'*%2)(#+3!&)!5+-)5+!&+!&(''*%**+!%-:1%!+!&(5)(!(!&+!*+)#'+7*%*/)3!)#!*%$$(*'(!%//%!,%*)%2)(#+!5)!$+&(!-.+!%66)%4(!*+7)&'*%'(8!b%'1*%/4+#'+3!/%!$+*5)'%!5)!$+&(!5+,+!+&&+*+!7*%51%/+3!+!0%*!$+*5+*+!%/!$%2)+#'+!1#B+--+&&),%!:1%#')'>!5)!-.)/)!?!5)00)-)/+G!(!&)!$*(/1#7%!)/!$+*)(5(!5)%/)')-(3!($$1*+3!&)!$*(-+5+!171%/4+#'+!+!)/!$%2)+#'+!$%7.+*>!)#!'+*4)#)!5)!&)#'(4)!/%!*%$)5%!-(#'*%2)(#+!5+//%!,(/+4)%G!)$('+#&)(#+3!#%1&+%3!,(4)'(8!!!

\(41#:1+3!&+!)/!$%2)+#'+!+&%7+*%!-(#!&(5)(!+!%-:1%!#+/!$+*)(5(!)#'+*5)%/)')-(3!/%!-(#&+71+#2%!?!-.+!)!/):1)5)!)#!+--+&&(!&)!,%##(!%5!%--141/%*+!#+!-(4$%*')4+#'(!%!

Page 106: sbobinature nefro_0 - SkyDrive

$*+&&)(#+!4)#(*+G!'%)6$%/$*(8!O)!.%!:1)#5)!+5+4%!$(/4(#%*+!#(#!-%*5)(7+#(!Y%#-.+!&!+$()!1#%!-(4$(#+#'+!-%*5)(7+#%!-B?!&+4$*+Z8!

"$+*]%/)+4)%!+5!+5+4%!$(/4(#%*+!#(#!-%*5)(7+#(!&(#(!%()-$/6%'-"*2()"-1#()3(%)6"2'(*#()'*)#(,"6'")3'"%'#'-"9)

"/!$%2)+#'+!-(#!)#&100)-)+#2%!*+#%/+!%,%#2%'%3!4%!%#-(*%!-(#!^k`!5)!WP!4/U4)#3!#(#!.%!+--+&&),)!$*(6/+4)!5)!(4+(&'%&)!)5*(&%/)#%G!0)/'*%!IPPP!4a:!5)!&(5)(!%/!7)(*#(3!$)F!(!4+#(8!L1+//(!-.+!$+*5+3!*)&$+''(!%//%!$+*&(#%!#(*4%/+3!?!/%!-"6"-'#:)3')"3"##"/(*#$),"6'3$!%//+!,%*)%2)(#)!6*1&-.+8!L1)#5)3!)#!&(&'%#2%3!)#!:1+&'(!&'%5)(!/B+--+&&(!5)!%$$(*'(!&(5)-(!,)+#+!$%7%'(!&($*%''1''(!-(4+G!

< S&&,"7"/(*#$)3(%%5'6(,#(*0'$*()< `$*+'$,()3(&%')",#')'*+(,'$,')< S1/(*#$)6$*3(,"%()< j$%#$)1*)6$5)(3(/"#$0$)

9,,)%4+#'+3!&+!1#!$%2)+#'+!5)!:1+&'(!')$(!,)+#+!&(''($(&'(!%!6*1&-.+!,%*)%2)(#)!Y)#'+&+!&($*%''1''(!-(4+!)4$*(,,)&+!-(#'*%2)(#)!5+//%!01#2)(#+!*+#%/+3!$+*!+&+4$)(!%!-%1&%!5+//B%&&1#2)(#+!5)!kMbO3!(!!%14+#'(!5+//%!$+*5)'%!5)!&(5)(!%!-%1&%!5)!5)%**+%Z3!)/!&1(!4+--%#)&4(!5)!-(4$+#&(!?!)#&100)-)+#'+!+!:1)#5)!*)&-.)+*>!5)!0%*+G!

< a5+4%!$(/4(#%*+!%-1'(!< "#&100)-)+#2%!*+#%/+!%-1'%!

M!&+-(#5%!5+/!-%&(8!!

!

94+(&'%&)!5+//B%-:1%!

"!&(77+'')!#(*4%/)!4%#'+#7(#(!/B(4+(&'%&)!5+//B%-:1%!%''*%,+*&(!/%!-%$%-)'>!5)!-(#-+#'*%*+!(!5)/1)*+!/+!1*)#+!+!%''*%,+*&(!/%!,%*)%2)(#+!5+//B)#'*()'(8!L1+&'+!01#2)(#)!&(#(!-(#'*(//%'+!)#!7*%#!$%*'+!5+//B(*4(#+!%#')5)1*+')-(!YM_lZ8!"/!&(77+''(!#(*4%/+!.%!/%!-%$%-)'>!5)!-(#'*%**+!/%!5)1*+&)!0)#(!%!SPP!4/U!5)+!%/!6)&(7#(3!4%#'+#+#5(!#+/!-(#'+4$(!/B+&-*+2)(#+!5+//+!&-(*)+!%2('%'+8!_B%/'*%!$%*'+3!/%!-%$%-)'>!5)!5)/1)*+!/+!1*)#+!?!$*+&&(-.[!)//)4)'%'%8!b+/!$%2)+#'+!-(#!)#&100)-)+#2%!*+#%/+3!$1*!+&&+#5(!#(*4%/+!)/!4+--%#)&4(!5)!&+-*+2)(#!5+//BM_l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a1"9)!'P)+,(a1(*#(/(*#(G)6(,vG)0')7(,'+'-")1*")-",(*2")3')"-a1"!-.+!)/!*+#+!$+*N!#(#!$+*-+$)&-+3!-(#')#1%#5(!:1)#5)!-(#!/%!&1%!5)1*+&)!0)&&%!5)!I<I3S!/)'*)!%/!7)(*#(G!%!:1+&'(!$1#'(3!&+!#(#!&)!)#'+*,)+#+3!/%!01#2)(#+!*+#%/+!*)&1/'+*>!%//%!0)#+!5+0)#)'),%4+#'+!-(4$*(4+&&%!5%//B)$(,(/+4)%!-.+!&)!,)+#+!%!5+'+*4)#%*+8!

!

94+(&'%&)!5+/!-%/-)(!+!5+/!0(&0%'(!

"/!$*)4(!+,+#'(!-.+!&)!,+*)0)-%!#+/!$%2)+#'+!-(#!*)512)(#+!5+//%!01#2)(#+!*+#%/+3!%#-.+!4(5+&')&&)4%3!?!)/!0%''(!-.+!)/!-%*)-(!5)!0(&0%'(!#(#!,)+#+!%5+71%'%4+#'+!+/)4)#%'(8!

Page 107: sbobinature nefro_0 - SkyDrive

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h3!(*4(#+!0(&0%'1*)-(8!L1)#5)3!/+!$)--(/+!,%*)%2)(#)!5)!0(&0%'+4)%!-%1&%'+!5%//%!*)512)(#+!5+//%!01#2)(#+!*+#%/+!-%1&%#(!,%*)%2)(#)!#+//%!&+-*+2)(#+!5+/!HVl3!-.+!'+#5+!%!*)$(*'%*+!'1''(!%//%!#(*4%/)'>8!EB(4+(&'%&)!,)+#+!4%#'+#1'(!0)#(!%!/),+//)!-(#!^k`!)#'(*#(!%)!KP!4/U4)#8!_%!:1+&'(!4(4+#'(!)#!$()3!)/!$%2)+#'+!-(4)#-)%!%5!+&&+*+!'6(,#',$'3($)I'6(,6","#',$'3'0/$)0(-$*3",'$J)!+!-(4)#-)%!%#-.+!%5!+&&+*+!)$+*0(&0%'+4)-(8!!

"/!5)&-(*&(!5+/!-%/-)(!?!-(4$/+'%4+#'+!5),+*&(8!"/!&(77+''(!-(#!"`!(,,)%4+#'+3!0)/'*%!4+#(!-%/-)(3!4%!#(#!?!:1+&'(!)/!&1(!$*(6/+4%8!"/!$1#'(!-*1-)%/+!?!-.+!)/!*+#+!6,$31-()'%)-"%-'#,'$%$)0$##$)%5'*+%1(*2")3(%)!8h9!"/!-%/-)'*)(/(!.%!&($*%''1''(!/B+00+''(!5)!"1/(*#",()%5"00$,C'/(*#$)'*#(0#'*"%()3(%)-"%-'$9)X%#(!%!4%#(!-.+!/%!01#2)(#+!*+#%/+!&)!*)51-+3!/%!-%$%-)'>!5)!%&&(*6)*+!)/!-%/-)(!&)!*)51-+!$*(7*+&&),%4+#'+!%!-%1&%!5+//%!$*+,%/+#2%!5+/!5+0)-)'!5)!,)'%4)#%!_!%''),%!&1//%!*)512)(#+!5+//B+&-*+2)(#+!*+#%/+!5+/!-%/-)(8!"/!$*(6/+4%!5+//%!)$(-%/-+4)%!5%!4%/%&&(*6)4+#'(!5)!-%/-)(3!?!-.+!+&&%!5),+#'%!)#+,)'%6)/4+#'+!/(!&')4(/(!%//%!&+-*+2)(#+!5)!HVl3!-.+!&%*+66+!4)*%'%!%!&')4(/%*+!/%!$*(512)(#+!5)!,)'%4)#%!_!+5!%14+#'%*+!:1)#5)!/B%&&(*6)4+#'(!5)!-%/-)(!)#'+&')#%/+!D!#+/!$%2)+#'+!-(#!)#&100)-)+#2%!*+#%/+3!$+*N3!:1+&'(!4+--%#)&4(!?!5+0)-)'%*)({!"/!HVl!.%!%#-.+!/%!01#2)(#+!5)!"##'7",()'%),'"00$,C'/(*#$)$00($3!$('+#2)%#5(!)#5)*+''%4+#'+!/%!01#2)(#+!(&'+(-/%&')-%8!L1+&'(!&)!,+*)0)-%!$*)#-)$%/4+#'+!)#!:1%#'(!)/!HVl!&')4(/%!7/)!(&'+(6/%&')!%//B+&$*+&&)(#+!5)!`Mbn<E3!-.+!)#'+*%7+#5(!-(#!`Mbn!+&$*+&&(!5%7/)!(&'+(-/%&')!%''),%!)/!*)%&&(*6)4+#'(!(&&+(!+!/%!5)00+*+#2)%2)(#+!'+*4)#%/+!5+7/)!(&'+(-/%&')8!L1+&'(!0%''(!-%1&%!(,,)%4+#'+!3"**$)0-.(%(#,'-$)I$0#($3'0#,$+'"),(*"%(J9))

L1)#5)3!+--(!-.+!/+!,)+!5+/!4+'%6(/)&4(!5+/!-%/-)(!+!5+/!0(&0%'(!&)!*)-(#7)1#7(#(G!)/!-%/-)(!/)6+*%'(!5%//+!(&&%!@)#-(#'*%A!)/!0(&0%'(!%--141/%'(!#+/!&%#71+!+!&)!0(*4%#(!6,(-'6'#"#'!)#!&+5+!%*')-(/%*+3!,%&-(/%*+3!$(/4(#%*+8!

!

Page 108: sbobinature nefro_0 - SkyDrive

!"#"$%&'()(*+()&$,-+&*&.()&$/&.(#0#+"$#"''1,2-'+&$

$

3*(*+"$0#)4"$'0$5&6.0$0-+&*&.()0$6")"**(70$"2$(#+"6"**0$('$80.8(#&9$:'$6"#"$;&'()(*+()&$2"''102-'+&$<$-#0$2"''"$+0#+"$;0+&'&=("$)(*+()4"$6"#0'(>$"2$<$0#)4"$'0$;(?$56"@-"#+"$+60$'"$.0'0++("$"6"2(+06("$0-+&*&.()4"$2&.(#0#+($2"''1-&.&9$$

$

$

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

G *&$+$",'#-!#(./%!0/$#+%&.%%.&$#1!+%!12$#"$/#0'&$"12!('#&$"'/$#G 3.($"%4#')"4&($#-$//$#-!($"+!4"!#-$/#&$"$#

H10-."#+&$2"'"$2(."#*(&#($2"'$6"#"$60;;6"*"#+0$-#$)0*&$"))"D(&#0'"$#"''10.8(+&$2"''"$;0+&'&=("$6"#0'($)6&#()4"9$I#$6"#"$;&'()(*+()&$;-J$;"*06"$20$KL=$0$MN$L=9$H1022&."$<$'06=0."#+"$&))-;0+&$20($6"#(>$)4"$70##&$0$)&.;6(."6"$'"$0#*"$(#+"*+(#0'(C$0#)4"$('$5"=0+&$(#$="#"6"$<$(#+"6"**0+&$20''"$)(*+(>$.0$@-"*+&$#&#$)0-*0$#"**-#$;6&8'".09$

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

$

Nefropatie ereditarie

Altre (non cistiche)

Nefropatie cistiche

ADPKD ereditarie acquisite

Imaging: A) RM

B) ecografia

A

B

F

Page 109: sbobinature nefro_0 - SkyDrive

!"#$%&%#'(")*)+,)*(#-#)&#$%.",/#0&.#!"#"$$%"&'$'()*'+'",&1&2)#,0,,(#3."#'0&,(#3)#4)+,.#5%&%,)*(#%+)+,(&(#30%#5%&)#*6%#'(++(&(#$),$(4.$+)#70,.,)8#

9 -)#%.%/$%+"&01&.()!)/)!"&02&34567589&9 -)#%.%/$%+"&:1&.()!)/)!"&;&3056:589&

:)#+(&(#'%$+(&%#*6%#+%7;$%$%;;%$(#&(&#%++%$%#'($,.,$)*)#3)#&%++0&.#3)#<0%+,%#30%#70,.2)(&)=#7.#0&#,%$2(#5%&%#&(&#-#.&*($.#+,.,(#)3%&,)>)*.,(?#@$(;.;)"7%&,%=#)&#7(",)#*.+)#%+)+,(&(#3)>%,,)#5%&%,)*)#7(",(#3)>>)*)")#3.#)3%&,)>)*.$%?##

A%#30%#7.".,,).#6.&&(#%++%&2)."7%&,%#".#+,%++.#+,($).=#*(&#0&B)7'($,.&,%#3)>>%$%&2.8##"&<'#).%$=&>%&?()*('//%)+',&C$(++(".&.7%&,%=#'$%&3%&3(#*(7%#$)>%$)7%&,(#)#'.2)%&,)#*(&#!"#"$$%"&.)+.#"!"$"1&+)#$),)%&%#*6%8#

9 D&#'.2)%&,%#*(&#7.".,,).#3%"#$%&%#'(")*)+,)*(#3)#,)'(#E#$.55)0&5.#"B)&+0>>)*)%&2.#$%&."%#,%$7)&."%#,$.#)#FG#%3#)#GG#.&&)=#+%&2.#3)>>%$%&2%#,$.#7.+*6)#%#>%77)&%H##

9 @%$#)#'.2)%&,)#*(&#7.".,,).#3)#,)'(#I=#)&4%*%=#+)#$),)%&%#*6%#"B%,/#7%3).#+).#3)#JK9LK#.&&)=#%#)&#."*0&)#*.+)#"(#+,.3)(#,%$7)&."%#&(&#4)%&%#$.55)0&,(?#

M55)=#'%$N=#*(&#"%#,%*&)*6%#%*(5$.>)*6%=#+)#-#*.'),(#*6%#%+)+,%#0&.#'%$*%&,0."%#7(",(#$)"%4.&,%#3)#+(55%,,)#*6%#6.&&(#0&.#'$(5$%++)(&%#7(",(#')O#"%&,.?#@$%&3%&3(#)&#%+.7%#."/%/$%.@'&'.)*("A%.@'=#+)#.$$)4.#.#+(+,%&%$%#*6%#)"#GKP#3%)#'.2)%&,)#*(&#$%&%#'(")*)+,)*(#3)#,)'(#!#$.55)0&5%#"B%,/#3)."),)*.#,$.#FG#%#GG#.&&)?#D&#.",$(#GKP#".#$.55)0&5%#')O#,.$3)4.7%&,%#(#&(&#"(#$.55)0&5%#7.)?##

Q++%&3(#0&.#7.".,,).#%$%3),.$).=#&%"".#+,$.5$.&3%#7.55)($.&2.#3%)#*.+)#)"#'.2)%&,%#6.#0&#*'+%$)('&!"#"$)?#:)#'(++(&(#%++%$%#,$%#%**%2)(&)8#

9 -"B%'+$%&.@'&+)+&.)+)/.)+)&%#&?()?(%)&<'()&?">('&9 -"B%'+$%&">)$$"$%&9 C"/%&!"#$%&%&

A%#'(")*)+,)&%#+(&(#'$(,%)&%#DE%FD%$"(%'#*6%#>($7.&(=#0&.#4(",.#+)&,%,)22.,%#%3#.++%7;".,%=#0&#."+"#'&?'(&%#&."#.%),&A.#'(")*)+,)&.#E#-#0&#$%*%,,($%#3)#7%7;$.&.#*.'.*%#3)#"%5.$+)#%3#)&,%$.5)$%#*(&#'$(,%)&%#R*("".5%&%=#>);$(9&%*,)&.=#".7)&)&.=#%**?S#*.$;()3$.,)#%#")')3)#3)#4.$)(#,)'(#%#3)#3%,%$7)&.$%#$)+'(+,%#)&,$.*%""0".$)#*(&#0&#7%**.&)+7(#*6%#'$%4%3%#".#>(+>($)".2)(&%?#

A.#'(")*)+,)&.#I#-#0&.#'$(,%)&.#,0;0".$%#*6%#>($7.#0&#*.&."%#'%$#

)"#*."*)(#%#>($+%#'%$#.",$)#*.,)(&)H#".#+0.#>0&2)(&%#-#'$(;.;)"7%&,%#<0%"".#3)#,$.+7%,,%$%#.""B)&,%$&(#3%"".#*%""0".#T+%5&.")U#3%$)4.&,)#3.""B)&,%$.2)(&%#>$.#".#'(")*)+,)&.#E#%#"B.7;)%&,%#%V,$.*%""0".$%?##

W0."%#+).#%+.,,.7%&,%#".#>0&2)(&%#3%"#*(7'"%++(#3%""%#'(")*)+,)&%#&(&#-#&(,(?#!#3.,)#+'%$)7%&,.")#'%$7%,,(&(#3)#)'(,)22.$%#*6%=#4%$(+)7)"7%&,%=#"%#'(")*)+,)&%#+).&(#3%'0,.,%#X#30$.&,%#".#>.+%#3)#+4)"0''(#3%""B)&3)4)30(#X#."".#+%5&.".2)(&%#*%""0".$%=#+'%*)."7%&,%#&%)#'$(*%++)#*6%#$)50.$3.&(#".#".FD%/%B%)+'&>'##"&?)#"(%$=&.'##D#"(',&&

ciglio primario

Regione baso-laterale

Page 110: sbobinature nefro_0 - SkyDrive

!"#$%&'()*+)#,-*."/&"#,*+*#$*0&),,)$"#"#,*+*#1)#+%$"/*,)#&).)2#!'#$'33)*/'+('#1"00"#$%&'()*+)#,*+*#1)#&).*#$),,"+,"2#4)#,)#5#-6)",&)#-*$"#$')7#+")#,*33"&&)#"&"/*()3*&)#."/#0'#$%&'()*+"7#)0#3"+"#,'+*#+*+#./*88"1'#'00'#-'/"+('#1)#./*&")+'9#)+#"::"&&)7#.'/"#-6"#;%",&*#'--'1'2#<00*/'7#0'#-*$.'/,'#1"00'#$'0'&&)'#.*0)-),&)-'#,)#8"/):)-6"/"=="#,*0*#)+#./","+('#1)#%+#!"#$%&'()*'-'.'-"#1)#-'%,'/"#%+'#$%&'()*+"#,*$'&)-'#'#-'/)-*#1"00>'0&/*#'00"0"7#,'+*2#?%",&'#&"*/)'#)$.0)-'#1)8"/,"#-*+,)1"/'()*+)@#

A +$%'*,**"'-"'#"--,-"'"!./)0$%$'-1'01-1**)12'B+:'&&)7#,)#-'0-*0'#-6"#+"0#/"+"#,*0*#0>CACDE#1"00"#-"00%0"#1)'+*#*/)3)+"#'00"#-),&)2#B+*0&/"7#0"#$'+):",&'()*+)#"F&/'/"+'0)#,*+*7#+"0#-*$.0",,*7#$*1",&"2##

A 31'.$-)#)!*)%14')%'.1/*)#$-1/"'%"-'/"%"4'51'6/"7,"%*"0"%*"')%#$%*/$'1'0,*18)$%)'!.$%*1%""2#

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

#

#

Proliferazione cellulare

Secrezione intracistica

AMPc - mediata

Page 111: sbobinature nefro_0 - SkyDrive

!"#$%&'!()*+','!

!" #$%$&'" (%)$*)+%,&-.'/0#,'()*'!.0*!()*)&1&-" .$/0),&&

23%4'!,3,,'!'!+)#,%,)#'!.'!#0&0!+)*'('4,'()!5%&&)!%&(50!('4,'!0+%,'(506!7&!*'&0%!.'!8%44'8%9!*0!('4,'!0+%,'(50!&)&!.%&&)!:3%4'!8%'!%*(3&!+#);*08%6!<((0=')&%*80&,0!3&%!('4,'!+3>!(#04(0#0!8)*,)!0!.%#0!*3)$)!%!4'&,)8%,)*)$'%!)4,#3,,'/%6!?)&)!#%#'!'!(%4'!'&!(3'!'*!@0$%,)!8)4,#%!3&!:3%.#)!4'8'*0!%!:30**)!#0&%*09!(%#%,,0#'==%,)!.%**%!+#040&=%!.'!'&&380#0/)*'!('4,'A!4'!+%#*%!%**)#%!.'!@0$%,)!+)*'('4,'()6!B0!+0#4)&0!()'&/)*,0!4)&)!$0&0#%*80&,0!.)&&0!'&!0,C!@0#,'*0A!+#);%;'*80&,09!$*'!)#8)&'!

Complicanze epatiche

Tutte estremamente rare ad eccezione delle delle cisti asintomatiche (80 – 90% dei casi) e del reflusso gastro- esofageo

Page 112: sbobinature nefro_0 - SkyDrive

!"!!#$%&'("))&*&%&'+$**,'#*'&)-,./$*/"'.#,%,0'''

!" #$%&'(1,!!,*,'"!!"."'-."!"*/&')$%(,.)$2&,*&'3$.4&$3+"5'!,-.$//#//,'-.,%$!!,')&/.$%&3,0'

)" *+,-(6%3#*&'&*4&7&4#&5'7".,!&)&%)"*/"'3,%-&/&'4$')#/$2&,*&'!-"3&(&3+"5'/"*4,*,'$'

!7&%#--$."'$*"#.&!)&'4"&'7$!&'4"%%$'8$!"'3.$*&3$0'''

1".'%$'4&$9*,!&'4"9%&'$*"#.&!)&'!&'4"7"'.&3,.."."'$%%$':;<0'<%'-.,8%")$'='3+"5'*"%'-$2&"*/"'3,*'&*!#((&3&"*2$'."*$%"'"'(&%/.$/,'9%,)".#%$."'&*(".&,."'$'>?')%@)&*'&%')"22,'4&'3,*/.$!/,'#/&%&22$/,'-#A'3$#!$."'#*$'9.$7&!!&)$'!&*4.,)"'!&)&%B!3%".,4".)&3$5'C#$!&'!")-."'($/$%"0''

D,)-%&3$*2"'."*$%&'

B ./-0,$11-2-'03+(&'0+4'(2&%0-2+5'3+"'='-.$/&3$)"*/"'&4"*/&3$'$'C#"%%$'3+"'!&'7".&(&3$'*"%%"')$%$//&$'."*$%&'3.,*&3+"5'3,*'%$'4&(("."*2$'4"%%E$!-"//,'),.(,%,9&3,'"'4"%%E$*")&$5'3+"'!-"!!,'=')"*,'$33"*/#$/$0''

B <%'-$2&"*/"'3,*')$%$//&$'-,%&3&!/&3$5'4&'!,%&/,'+$'#*$'-5'&6'0,-%0'(,'7'&+('(5&'2%2''3+"'9"*".$%)"*/"'&*!,.9"'$'F?BFG'$**&0'H'#*E&-"./"*!&,*"'4&'<<<'9.$4,'4&((&3&%)"*/"'3,*/.,%%$8&%"5'-".'%$'C#$%"'!&'#/&%&22$*,'-,%&/".$-&$'3,*'I5G','$44&.&//#.$'J'($.)$3&'4&7".!&'K/.$'3#&'C#$!&'!")-."'&%':&*,L&4&%M0'NE&-"./"*!&,*"'!&'!#--,*"'"!!"."'%"9$/"'$4'#*E$8*,.)"'-.,4#2&,*"'4&'."*&*$'4$'-$./"'4"%'-$."*3+&)$'."*$%"'3,)-."!!,0'

'

Aneurismi intracranici

Page 113: sbobinature nefro_0 - SkyDrive

!

!"#$%$&'()'*+,-#*+./$(0-+#1+,$2#'()'+34#1/,,$+#(3/55#6#'(2$+%'($1'+6%-(#6$+3#+3-&&$+$(6"'+#1+6-()%#7/)-+0'11$+%#)'(2#-('+#0%-3-0#6$+('11$+8'('3#+0'119#,'%)'(3#-('+'+('1+3/-+,'88#-%$&'()-:+

;,#0'&#-1-8#6$&'()'*+19#,'%)'(3#-('+"##$"%"+19$(0$&'()-+0'11$+&$1$))#$*+'+#1+)%$))$&'()-+$()#,'%)'(3#4-+&'&!(')*+*,"!-."&)"(/&0'!)/--"!("-"00*"+$(6"'+3'+,'%&'))'+#1+6-()%-11-+0'119#,'%)'(3#-(':++

< =$+&$1$))#$+>+$"$"(/&0/!1$'0/*&2$*,"+'+#1+)%$))$&'()-+$))-+$+,%'4'(#%'+1$+,%-8%'33#-('+?@!;<A*+0#')$*+'66::B+0#+3-1#)-+(-(+&-0#5#6$+$33-1/)$&'()'+#1+0'6-%3-:++

< 3("02$*"!(",$'4,'1*,"!&/-!567!)/*!,"4*!

!

< 8&+/9*'&/!)/--/!,*40*++

< :"-,'-'4*!$/&"-*!

=9$3,'))-+3#()-&$)-1-8#6-+6"'+,'3$+,#C+('11$+4#)$+0'1+,$2#'()'+>+#1+)'-'$/;!A1+0-1-%'+>+0#+0/'+)#,#D+

< <'-'$/!,$'&*,'!,'&0*&2'=!4'$)'=!%*4,/$"-/D+>+1'8$)-+$119'3,$(3#-('+0'11$+&$33$:++

< 31*4')*!)'-'$'4*!",20*!0-4/)#+$119#(3-%8'(2$+0#+$16/('+6-&,1#6$2#-(#*+6-&'D+$: A&,'8(-+0#+/(+6$16-1-+('119/%')'%'+7: ;&-%%$8#$+$6/)$+#()%$6#3)#6$+6: A(5'2#-('+0#+/($+6#3)#+

A1+)%$))$&'()-+0'119'&-%%$8#$+#()%$6#3)#6$+-+0'119#(5'2#-('+0#+/($+6#3)#+>+6-(3'%4$)#4-*+-44'%-*+(-(+3#+5$+$33-1/)$&'()'+(#'()'*+$+0#55'%'(2$+0#+./$(0-+./'3)'+6-&,1#6$(2'+3#+

Ipertensione - patogenesi

• Compressione • Ischemia • Produzione di renina da parte dell’epitelio delle cisti

"   > ET1 "   > SNS "   alterazione del rapporto BP/natriuresi

Page 114: sbobinature nefro_0 - SkyDrive

!"#$%$&'$()*$(*+(,*&$-.$*"/,.$&,*0*$(*.,1*&,-)2*$(%,..$2*-$*/#)&"3"*,1*3#"(,44$)5*6"#*17$(%"8$)("*3"11,*&$-.$*#"(,1"*&$*-$*1$9$.,*,11,*."#,/$,*,(.$:$).$&,5*

*

;$,4()-$*

<,*3$,4()-$*3$*9,1,..$,*/)1$&$-.$&,*&)(&1,9,.,*=*-"9/1$&"5*>1*/#):1"9,*!"#)*3"11,*9,1,..$,*/)1$&$-.$&,*#"(,1"*=*1)*-&#""($(45**

?,#"*)*()(*%,#"*1)*-&#""($(4@*

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

G*<,*/#"-"(8,*3$*,19"()*H*&$-.$*/"#*#"("*I$(*+(*-)44"..)*,3+1.)*)*,(8$,()J5*

G*<,*/#"-"(8,*3$*K*&$-.$*I$(*+(*4$)!,("J5*L"*+(*4$)!,("*',*3+"*&$-.$*"3*$*4"($.)#$*-)()*9,1,.$2*=*-$&+#,9"(."*,%%"..)*3,*#"("*/)1$&$-.$&)5*L"*+(*4$)!,("*',*3+"*&$-.$*"*$*4"($.)#$*-)()*-,($2*',*&)9+(C+"*$1*MNGONP*3$*/#):,:$1$.E*3$*"--"#"*9,1,.)5**

<,**3$,4()-$*4"(".$&,*=*)!!$,9"(."*/)--$:$1"5*>(*4"("#"*-$*%,*+()*-.+3$)*3$*1$(Q,4"*3$-"C+$1$:#$+9F*-)()*/)&'$*$*&"(.#$*&'"*"%%"..+,()*$1*-"C+"(8$,9"(.)*3$#"..)5*

*

R"#,/$,*

A"41$*+1.$9$*,(($*-)()*-.,.$*/#)/)-.$*3$!"#-$*/)--$:$1$*$(."#!"(.$*."#,/"+.$&$*/"#*$1*#"("*/)1$&$-.$&)2*()(*.,(.)*/"#*.#,..,#"*17$(-+%%$&$"(8,*#"(,1"2*C+,(.)*/"#*&)(.#)11,#"*1,*9,1,..$,5*

S7*-.,.)*3$9)-.#,.)*&'"*17"!)1+8$)("*3"11,*9,1,..$,*-+1*/$,()*&1$($&)*3$/"(3"*3,11"*!"#$"%$&'$()*+,*'%$"-$(.*-(!&-,/*(.*$(#*'$0(T+"-.)*)44$*&$*/"#9".."*3$*$3"(.$%$&,#"*$*-)44"..$*&'"*/)--)()*#,4$)("!)19"(."*,.."(3"#-$*+(,*%$("-.#,*3$*UNGVN*,(($*-"(8,*$9/)#.,(.$*"!)1+8$)($5*T+"-.,*!,1+.,8$)("*-$*"%%"..+,*"%%"..+,(3)*3$!"#-"*-&,(-$)($*WX>*,*3$-.,(8,*3$*V*9"-$*17+(,*3,117,1.#,*"3*)--"#!,(3)*17"(.$.E*3"11,*!,#$,8$)("*!)1+9".#$&,5*

<"*1$(""*."#,/"+.$&'"*-)()*3"$*3+"*.$/$B*

10 2&33#*))$&'*(.*--4567(

L)//#$9"(3)*17Y;Z2*-$*"!$.,*17,&&+9+1)*3$*1$C+$3)*,117$(."#()*3"11"*&$-.$*"*C+$(3$*1,*1)#)*"-/,(-$)("5*6"#*-)//#$9"#"*17Y;Z*-$*/)--)()*:"#"*U*1$.#$*3$*,&C+,*,1*4$)#()2*)//+#"*-$*/+[*+-,#"*+(*,(.,4)($-.,*-/"&$%$&)*3"$*#"&"..)#$*\K*3"117Y;Z5*T+"-.,*-.#,."4$,*-$*=*#$!"1,.,*,::,-.,(8,*3"1+3"(."5*

80 9*#"3$"(:$;&);";$:"(

<"*&"11+1"*3"11"*&$-.$2*,1."#,."2*-"9:#,()*"--"#"*/,#.$&)1,#9"(."*-"(-$:$1$*,1*:1)&&,44$)*3"11,*!$,*3$*-"4(,1,8$)("*3$*/9<=*"*C+$(3$*-)()*-.,.$*/#)!,.$*%,#9,&$*&'"*,4$-&)()*-+*C+"-.,*!$,*I.,&#)1$9+-2*-$#)1$9+-2*"!"#)1$9+-2*."9-$#)1$9+-]J5*>*.#$,1-*&)(.#)11,.$*

Page 115: sbobinature nefro_0 - SkyDrive

!""!##$%#&'"&()*%'+)()'+#%#&',!-$,!(#&.'/%'+)()'+#%#&'0)(,)##&'+)-)'+$'1!*+)(!'0)('/%-%##&%'%2%(3%#%4'5'*&+$-#%#&',!--!'%11-&0%3&)(&'0-&(&06!'+$&'1%3&!(#&'#*%##%#&')""7-%8!-.'0)/$(9$!.'+)()'&(0)*%::&%(#&4''

Page 116: sbobinature nefro_0 - SkyDrive

!"#$%#&'()*+&#,+)

-,)'"#$%#&'()"+&#,+).),/#,'+"&#'%0#)#,,#)1%#,%2%)&+,,#)'+"#$%#)2(2'%'3'%0#)1+,,/%&2344%5%+&6#)"+&#,+)'+"7%&#,+8)9+,),3&:()$+"%(1(;)%,)'"#$%#&'()"+&#,+)<#)3&)5(2'()1+5%2#7+&'+)0#&'#::%(2()"%2$+''()#,,#)1%#,%2%=)2%)2'%7#)%&4#''%)5<+),#)$"(5+13"#)'"#$%#&'(,(:%5#)+)%)23(%)5("(,,#"%)$+2%&()23,)2%2'+7#)2#&%'#"%()&#6%(&#,+)5(7+)>;?)#&&%)1%)'+"#$%#)1%#,%'%5#;)5(&),#)1%44+"+&6#)5<+)%,)'"#$%#&'()"+&#,+)5(&2+&'+)#)7(,'%)$#6%+&'%)1%)5(&13""+)3&#)0%'#)$"#'%5#7+&'+)&("7#,+;)#)1%44+"+&6#)1+,,#)'+"#$%#)1%#,%'%5#;)5<+)1+0+)+22+"+)+44+''3#'#)'"+)0(,'+)#)2+''%7#&#;)5(&)'3''%)%)1%2#:%)1+,)5#2(8))

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

)

!"#$%#&'%)+1)%773&%'I)

J#,)$3&'()1%)0%2'#)5,#22%4%5#'%0(;)+2%2'(&()'"+)'%$%)1%)'"#$%#&'()"+&#,+=)

K !"#$%#&'()%*(+,&%-()L00+"(;)%,)'"#$%#&'()%&)53%)%,)1(&#'("+).)3&):+7+,,()(7(6%:('+)1+,)$#6%+&'+8)E3+2'()5(7$("'#),/%1+&'%'I)1+:,%)#&'%:+&%)MHN;)+)D3%&1%)1%):"#&),3&:#),/(3'5(7+)7%:,%("+8)

)

K !"#$%#&'()#..(+,&%-()O/)%,)'"#$%#&'()1#)1(&#'("+)37#&():+&+'%5#7+&'+)1%0+"2(8)9+,)5#2()1%):+&%'("%;)4"#'+,,%)+)$#"+&'%;)#,53&%)#,,+,%)MHN)2#"#&&()$"+237%G%,7+&'+)%1+&'%5%8))

)

K !"#$%#&'()/,&(+,&%-()O/)%,)'"#$%#&'()5(&)(":#&()$"+,+0#'()1#)3&)#&%7#,+C)&+,,/3(7()&(&).)$"#'%5#'(8)

-,)$"(G,+7#)4(&1#7+&'#,+)1+,)'"#$%#&'()#,,(:+&%5().)(00%#7+&'+)%,)"%+,''()1+,):"#4'8)-,)"%:+''()2%)0+"%4%5<+"+GG+)7#'+7#'%5#7+&'+)2+)&(&)"%5(""+22%7()#,,#)'+"#$%#)%773&(2($$"+22%0#=)D3+2'(;)$+"5<P),+)5+,,3,+)1+,)1(&#'("+)+2$"%7(&()7(,+5(,+)1%44+"+&'%)1#)D3+,,+)(7(,(:<+)1+,)"%5+0+&'+;)%,)53%)2%2'+7#)%773&%'#"%()'+&1+)%&+0%'#G%,7+&'+)#)"%5(&(25+"+)5(7+)+2'"#&++;)+)13&D3+)#)7(&'#"+)3&#)"%2$(2'#)%773&%'#"%#)5<+)<#)5(7+)"%23,'#'()4%&#,+),#)$+"1%'#)1+,,/(":#&()'"#$%#&'#'()5(&)'+7$%2'%5#)0#"%#G%,+8))

H#)G#2+)1+,)"%-(&(*-%0,&'()1+,,+)7(,+5(,+)5(7+)Q2+,4R)()Q&(&K2+,4R).)(00%#7+&'+)1#)"%5+"5#"+)&+,)2%2'+7#)1+:,%)#&'%:+&%)1+,)5(7$,+22()7#::%("+)1%)%2'(5(7$#'%G%,%'I)AMHNB8)S(7+)2#$$%#7(;),+)7(,+5(,+)MHN)2(&()5(1%4%5#'+)1#)3&)5,32'+")1%):+&%)23,)G"#55%(),3&:()1+,)5"(7(2(7#)T)5<+)5(1%4%5#&()$+")$"('+%&+)1+4%&%'+)1%)5,#22+)-)+)1%)5,#22+)--8)H+)

Page 117: sbobinature nefro_0 - SkyDrive

$"('+%&+)1%)5,#22+)-)5(&2'#&()1%)3&#)5#'+&#)!)G%#,,+,%5#)5<+)0%+&+)+2$"+22#)23,,#)7+7G"#&#)%&)#22(5%#6%(&+)#,,#)"UK7%5"(:,(G3,%&#8)O2%2'(&()1%0+"2%),(5%)MHN)1%)5,#22+)-;)53%)5(""%2$(&1(&()#,'"+''#&'%)#,,+,%=)

K 12343)K 12345)K 12346)K 12347)K 12348)K 12349)

V%)2(&()$(%),+)7(,+5(,+)1%)5,#22+)--;)5%#253&#)5(2'%'3%'#)1#)13+)5#'+&+)A3&#)!)+)3&#)"B)G%#,,+,%5<+)5<+)$(22(&()5(7G%&#"2%)%&)7(1()0#"%()A+2=),#)5#'+&#)!)1%)3&)#,,+,+)$3@)'#,0(,'#)5(7G%&#"2%)5(&),#)")1%)3&)#,'"()#,,+,+B8)E3+2'%)#,,+,%)2(&(=)

K 1234:;))K 1234:<)K 1234:=)

;,")->%?)(+&%)%&@%A%@>(),",@%'#)@#%)$"($"%)+,&%'("%)>&)#$.('%$()B5%(.;)3&)$#55<+''():+&%5()1%)5#'+&#)!)+)")#22(5%#'+B)0#',"&(),@)>&()$#',"&(C))

H+)7(,+5(,+)WMS)2(&()%&):"#1()1%)$"+2+&'#"+)$%55(,%)$+$'%1%)1+"%0#'%)1#)$"('+%&+)%&'"#5+,,3,#"%)AWMSK-B)+1)+X'"#5+,,3,#"%)AWMSK--B;)#&5<+)2+)D3+2'#)1%2'%&6%(&+)&(&).)2+7$"+)"%2$+''#'#)A5"(22K$"+2+&'%&:B8)H+)7(,+5(,+)WMS;)D3%&1%;)2+"0(&()$+")4#"+)2Y)5<+)%),%&4(5%'%)!))2$+5%4%5%)$+")3&)1+'+"7%&#'()#&'%:+&+)"%5(&(25#&()'#,+)#&'%:+&+)+)7(&'%&()D3%&1%)3&#)"%2$(2'#)%773&%'#"%#)2$+5%4%5#)5(&'"()1%)+22(8)Z+"5<P)D3+2'()2%)0+"%4%5<%;)2(&()&+5+22#"%+)13+)5(&1%6%(&%=)

K D.).%&E(-%'#)!)@,A,)"%-(&(*-,",)*(.()#&'%+,&%)&(&4*,.E;)1#'()5<+)'"#)%)$+$'%1%)$"+2+&'#'%)1#,,+)7(,+5(,+)WMS)0%)2(&()2($"#''3''()7(,+5(,+)1+"%0#'+)1#,,#)1%:+2'%(&+)1%)$"('+%&+)2+,48)H+)7(,+5(,+)WMS;)%&2(77#;)$"+2+&'#&()3&)

Page 118: sbobinature nefro_0 - SkyDrive

Q5#7$%(&#7+&'(R)1+:,%)#&'%:+&%)%&'"#5+,,3,#"%)+1)+X'"#5+,,3,#"%;)#)$"+25%&1+"+)1#,,/("%:%&+)+,)4()&(&)2+,4)1+:,%)#&'%:+&%8)

K D.).%&E(-%'#)!)@,A,)"%-(&(*-,",)%)$,$'%@%)#&'%+,&%-%)*(.()F>#&@()$",*,&'#'%)@#)0(.,-(.,)G16)*,.E8)S%(.;)%,),%&4(5%'#)1+0+)%&'+"#:%"+)2(,()5(&),+)7(,+5(,+)WMS)1+,,/(":#&%27()#,)D3#,+)#$$#"'%+&+8))

E3+2'%)"+D3%2%'%)0+&:(&()(''+&3'%)7+1%#&'+)%,)$"(5+22()1%)2+,+6%(&+)1+%),%&4(5%'%)13"#&'+),#),("()7#'3"#6%(&+=)%),%&4(5%'%)"+#''%0%)5(&'"()#&'%:+&%)2+,4)0+&:(&()+,%7%&#'%;)+)5(2Y)$3"+)%),%&4(5%'%)5<+)&(&)2(&()%&):"#1()1%)%&'+"#:%"+)5(&),+)7(,+5(,+)WMS)2+,4)13"#&'+),#)7#'3"#6%(&+)&+,)'%7(8)Z"(5+22%)#&#,(:<%)2%)20(,:(&()#&5<+)&+,,#)7#'3"#6%(&+)1+,,+)5+,,3,+)[8))

L"#;)D3+,,()5<+)5%)1(GG%#7()5<%+1+"+).=)5(2#)2355+1+)D3#&1()3&)$#6%+&'+)"%5+0+)3&)(":#&()1#)3&)1(&#'("+)5<+)&(&)2%#)3&):+7+,,()(7(6%:('+\)L00+"(;)D3#,).),#)G#2+)1+,)"%:+''(\)H+)5%"5(2'#&6+)5<+)$("'#&()#,,/#''%0#6%(&+)1+,,#)"%2$(2'#)%773&%'#"%#)2$+5%4%5#)$(22(&()+22+"+)1%2'%&'+)%&)13+):"#&1%)'%$%=)$",*,&'#H%(&,)@%",''#)+1)%&@%",''#C))

H#)$",*,&'#H%(&,)@%",''#).)3&)4+&(7+&()$%3''(2'()5(7$,+22(8)Z"+0+1+)4(&1#7+&'#,7+&'+)13+)1%0+"2+)2%'3#6%(&%C),#)$"+2+&'#6%(&+)1%"+''#)$"+0+1+)%,)"%5(&(25%7+&'()1#)$#"'+)1%)3&),%&4(5%'#)!)1+,)"%5+0+&'+)1%)3&)5(7$,+22()WMSK&(&)2+,4)+)$+$'%1+)&(&K2+,4)$"+2+&'+)&+,,/(":#&()1+,)1(&#'("+8)-),%&4(5%'%)!)1+,)"%5+0+&'+;)%&)'+("%#;)&(&)$('"+GG+"()"%5(&(25+"+)7(,+5(,+)WMS)&(&)2+,4)$(%5<P)2(&()2'#'%)"%2'"+''%)$+")WMS)2+,48)E3+2'()$3@)$+"@)#55#1+"+)%&)D3+2'+)5(&1%6%(&%=)

#I D).%&E(-%'%)!)@,.)$#H%,&',)"%-(&(*-(&()>&#)0(.,-(.#)G16)#..(+,&%-#)A5%(.;)23)3&#)5+,,3,#)NZS)$"(0+&%+&'+)1#,,/(":#&()"%5+03'(B)$(%-JK).#)0("E(.(+%#)@%)F>,*'#)0(.,-(.#)0%0#)>&)-(0$.,**()E("0#'()@#)0(.,-(.#0)G164*,.E),)$,$'%@,)&(&4*,.EC))

LI D).%&E(-%'%)!)@,.)$#H%,&',)"%-(&(*-(&()>&)-(0$.,**()G164#..(+,&%-()M)$,$'%@,)&(&)*,.E)%&)D3#&'()'#,+)5(7$,+22()7(,+5(,#"+)7%7#)3&)5(7$,+22()WMSK2+,4)])$+$'%1+)&(&)2+,4)$+")53%)'#,+),%&4(5%'#).)2$+5%4%5(8))

<>,*'#)N).#)$",*,&'#H%(&,)@%",''#C)S(7+)2%)0+1+;)+22#)"%5<%+1+),#)$"+2+&6#)1%)5+,,3,+)1+&1"%'%5<+)1+,)1(&#'("+;)+),#),("()7#'3"#6%(&+)43&6%(&#,+8)^)2'#'()(22+"0#'()5<+;)&+,)"+&+)1+,)1(&#'("+;),()2'"+22)1#)%25<+7%#_"%$+"432%(&+)A5<%#"#7+&'+)%&+0%'#G%,+)&+,,#)$"(5+13"#)'"#$%#&'(,(:%5#B)$"(135+)2'%7(,%)5<+)%&135(&(),#)7#'3"#6%(&+)A+2=)+2$"+22%(&+)1%)7(,+5(,+)5(2'%7(,#'("%+)5(7+)[`B)+),/#''%0#6%(&+)1+,,+)5+,,3,+)1+&1"%'%5<+;)+,+7+&'()5"35%#,+)$+"),#)$"+2+&'#6%(&+)1+,,/#&'%:+&+)'"#7%'+),#)0%#)1%"+''#8)^)2'#'()%&(,'"+)(22+"0#'()5<+;)#,)5(&'"#"%(;),+)5+,,3,+)1+&1"%'%5<+)%77#'3"+)1+,)1(&#'("+)$('"+GG+"()+2+"5%'#"+)3&)+44+''()#11%"%''3"#)'(,,+"(:+&%5(=)$+"'#&'()#$$#"+)5"35%#,+),#)"%5+"5#)&+,)5#7$()1+,)1#&&()1#)%25<+7%#_"%$+"432%(&+8))

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

Page 119: sbobinature nefro_0 - SkyDrive

)

E3+2'+)2(&(),+)G#2%)1+,)"%:+''(;)#)53%)1(GG%#7()#::%3&:+"+)3&)#,'"()#2$+''()+2'"+7#7+&'+)%7$("'#&'+=),#)-(0$#'%L%.%'O)35PC)a,%)#&'%:+&%)N[b)2(&()+2$"+22%;)(,'"+5<P)23:,%)+"%'"(5%'%;)23,,+)5+,,3,+)+&1('+,%#,%8)c+)&(&)0%+&+)"%2$+''#'#),#)5(7$#'%G%,%'I)N[b;)%,)"%5+0+&'+)%&%6%+"I)%77+1%#'#7+&'+)#)4("7#"+)#&'%5("$%)1%"+''%)5(&'"():,%)#&'%:+&%)N[b)1+,)1(&#'("+;)5(2%55<P),/+&1('+,%()2#"I)($2(&%66#'()+)2%)#0"I)#''%0#6%(&+)1+,)5(7$,+7+&'()5(&)5(&2+:3+&6+)1%2#2'"(2+8)N)D3+2'#)"+:(,#;)5(73&D3+;)0%)2(&()#,53&+)+55+6%(&%8))

)

TCR

Nucleo

Citoplasma

APC HLA

Calmodulina

Ca++

Canali del Ca

NFAT

Fosfatasi

Trascrizione citochine pro-infiamm.,CD40L

Calcineurina CNA

Linfocita T

Page 120: sbobinature nefro_0 - SkyDrive

H/MHN)&+,,#)5,%&%5#)

H#)"%325%'#)1+,)'"#$%#&'(;)5(73&D3+;)2+7G"#)+22+"+),+:#'#)2($"#''3''()#,)7#'5<%&:)1%)#,53&%)#$,('%$%)MHN;)(00+"(),/N;)%,)[)+1)%,)J*8)c%).)0%2'()5<+),#)2($"#00%0+&6#).)%&0+"2#7+&'+)$"($("6%(&#,+)#,)&37+"()1%)7%27#'5<=)

)

H#):+2'%(&+)1+,,/#2$+''()%773&(,(:%5()1+,)'"#$%#7'()0%+&+)+44+'3#'#)%&)'"+)$"%&5%$#,%)7(7+&'%=)

K !%$%HH#H%(&,)'%**>'#.,)K Q-",,&%&+)#&'%-("$#.,)K 6"(**40#'-J)$",4'"#$%#&'()

)RC !%$%HH#H%(&,)123)

H#)'%$%66#6%(&+)MHN)0%+&+)+44+''3#'#)&+%)$#6%+&'%)%&)#''+2#)1%)'"#$%#&'(;)23,)1(&#'("+)#,)7(7+&'()1+,)$"+,%+0()1+,,/(":#&(;)+)23)'3''%)%)5#&1%1#'%)1(&#'("%)A+2=)$#"+&'%)+)&(&B8)c%)#"'%5(,#)%&)13+)'%$%)1%)%&1#:%&+=)

K !%$%HH#H%(&,)*%,"(.(+%-#;)5<+)2%)#00#,+)1%)2%+"%)2$+5%4%5%)$+")%1+&'%4%5#"+):,%)#&'%:+&%)1%)5,#22+)-)AN;)[;)SdB)+)--)AJZ;)JE;)J*B8)

K !%$%HH#H%(&,)0(.,-(.#",?)5%(.),/%&1#:%&+)5<+)$+"7+''+)1%)2+D3+&6%#"+)%),(5%)5(""%2$(&1+&'%)#%)0#"%)#,,+,%)#,)4%&+)1%)%1+&'%4%5#"+):,%)2$+5%4%5%)#$,('%$%8)

)

SC Q-",,&%&+)#&'%-("$#.,)

H()25"++&%&:)#&'%5("$#,+)2%)$(&+)+22+&6%#,7+&'+)13+)(G%+''%0%=)

K D&@%A%@>#",),A,&'>#.%)#&'%-("$%)#&'%4123)&,.)*%,"()@,.)$#H%,&',)

Page 121: sbobinature nefro_0 - SkyDrive

K Q,)*(&()$",*,&'%)#&'%-("$%?)A,"*()F>#.,)#&'%+,&,)*(&()@%",''%)A)O2=)JE\)JZ\)e\BT)U,"*()F>#.,)$#"'%-(.#",)#$.('%$()AO2=)JEf\)JEU\888BT):%)-J,)-.#**,)*(&(T)<>#&'%)*(&(T)

)

VC 6"(**40#'-J%&+)

-,)5"(22K7#'5<%&:).),/3,'%7()(2'#5(,()$"%7#)1%)$"(5+1+"+)#,)'"#$%#&'(8)-&):+&+"+)2%)+44+''3#)5%7+&'#&1()+"%'"(5%'%)1+,)1(&#'("+)5(&)%,)2%+"()1+,)$#6%+&'+;)+)(22+"0#&1()2+)0%).)"+#''%0%'I8)-&)5#2()$(2%'%0(;)&(&)2%)$3@)$"(5+1+"+)#,)'"#$%#&'(8)-&)5#2()&+:#'%0(;).)$(22%G%,+)$"(5+1+"+)#,)'"#$%#&'(8)-,)5"(22K7#'5<%&:)+2$,("#)2(2'#&6%#,7+&'+)#&'%:+&%)5(7+):,%)N[b;),/*<)+1)%,)g+,,8))

)

S"%'+"%)1%)#,,(5#6%(&+)1%)(":#&%)1#)5#1#0+"+)

h&()1+:,%)#2$+''%)5"35%#,%)1+,,#)'"#$%#&'(,(:%#).)'+&'#"+)1%)1%2'"%G3%"+):,%)(":#&%)1%2$(&%G%,%)5(&)+D3%'I;)2+5(&1()5"%'+"%)+'%5%)+)25%+&'%4%5%8)V+1%#7()#,,("#)D3#,%)2(&(),+)"+:(,+)$%F)4"+D3+&'+7+&'+)2+:3%'+;)%&)("1%&+)1%)%7$("'#&6#=)

RC 6(0$#'%L%.%'O)'"#)@(&#'(",),)"%-,A,&',)Z(5()1#)1%"+)23)D3+2'(=).),#)5(&1%'%()2%&+)D3#)&(&8))

SC Q(0%+.%#&H#)@%),'O)'"#)@(&#'(",),)"%-,A,&',)L00+"(;)'+&'%#7()&+%),%7%'%)1+,)$(22%G%,+)1%)&(&)#22+:&#"+)#1)3&)"#:#66(),/(":#&()$"+,+0#'()1#)3&#)$+"2(&#)#&6%#&#;)+)0%5+0+"2#8)S+"5<%#7()D3%&1%)1%)4("&%"+)#%)$#6%+&'%)1#)'"#$%#&'#"+)3&)"+&+)5(&)3&#)$"+237%G%,+)43&6%(&+)"+&#,+)%&),%&+#)5(&)D3+,,#)#''+2#)$+"),/+'I)1+,)$#6%+&'+8))

VC !,0$()@%)#'',*#)L00+"(;)2%)'+&'#)1%)1#"+),#)$"+5+1+&6#)#%)$#6%+&'%)5<+)2%)'"(0#&()1#)$%F)'+7$()%&),%2'#)1/#''+2#8)E3+2'()&(&)2+7$"+).)$(22%G%,+;)2($"#''3''()%&)"+,#6%(&+)#,,+)$"%7#)13+)"+:(,+)5<+)#GG%#7()5%'#'(8)

S(7+)0#,3'%#7(),#)-(0$#'%L%.%'OT)-&)$#"'+)+"#):%I)0+&3'()43("%)$"+5+1+&'+7+&'+8)N&6%'3''(;).)&+5+22#"%#),#)5(7$#'%G%,%'I)1+:,%)#&'%:+&%)+"%'"(5%'#"%;)2+5(&1()D3+2'+)"+:(,+=)

-&)"+#,'I;)0%)2(&()3&)5+"'()&37+"()1%)5+&'"%)5<+)<#&&()#5D3%2%'()3&#)5+"'#)+2$+"%+&6#)#&5<+)&+,)'"#$%#&'()N[b)%&5(7$#'%G%,+C)%)$"('(5(,,%)2%)G#2#&()+22+&6%#,7+&'+)23,)"%5("2()#1)3&#)'+"#$%#)%773&(2($$"+22%0#)$%F)#::"+22%0#)+)#,,#)$,#27#4+"+2%)#,,()25($()1%)#,,(&'#&#"+)1#,)$,#27#),+)%773&(:,(G3,%&+)#&'%K#&'%:+&%)+"%'"(5%'#"%)$"(1(''+)1#,)$#6%+&'+8)-&),%&+#)1%)$"%&5%$%(;)5(73&D3+;),#)5(7$#'%G%,%'I)N[b).)&+5+22#"%#8))

)

)

Page 122: sbobinature nefro_0 - SkyDrive

)

)

)

)

)

E3+2'#)'#G+,,#)%&0+5+)5%)7(2'"#)%,)$3&'+::%()5<+)0%+&+)#''"%G3%'()#,,+)0#"%+)2%'3#6%(&%)1%)7%27#'5<)MHN8)Z*N)2'#)$+")Q$#&+,)"+#5'%0+)#&'%G(1%+2R=).)3&)$#"#7+'"()5<+)2%)"%4+"%25+)#)'+2')2%+"(,(:%5%)4#''%)23,)2%+"()1+,)$#6%+&'+)+)0(,'%)#,,#)1%7(2'"#6%(&+)1%)#&'%5("$%)#&'%K#&'%:+&%)

37#&%C)2%)+2$"%7+)%&)$+"5+&'3#,+;)%&'+2#)5(7+)Q$+"5+&'3#,+)1%)%&1%0%13%)&+,,#)$($(,#6%(&+):+&+"#,+)0+"2()%)D3#,%)%,)2%+"()1+,)$#6%+&'+)2#"+GG+)"+#''%0(R8))

Z+")D3#&'()"%:3#"1#)%,)5"%'+"%()1+,,/,'O?)2%)2+:3+)%&):+&+"#,+)D3+2'#)"+:(,#=)

)

)

)

FASCE DI ETA’

•  DONATORE •  A 16 – 30 •  B 31 – 50 •  C 51 – 60 •  D 61 – 70 •  E > 70

•  RICEVENTE •  A1 16 – 45 •  B1 42 – 59 •  C1 60 – 66 •  D1 > 66

SCORE USED FOR THE SELECTION OF PATIENTS IN LIST FOR CADAVER KIDNEY TRANSPLANT

Page 123: sbobinature nefro_0 - SkyDrive

!+"#$%#)%773&(2($$"+22%0#)

)

)

H#)'+"#$%#)%773&(2($$"+22%0#)<#)"%0(,36%(&#'(),#)'"#$%#&'(,(:%#)A+),#)7+1%5%&#)%&):+&+"#,+B8)H#)0+"#)"%0(,36%(&+).)2'#'#)"#$$"+2+&'#'#)2%53"#7+&'+)1#,,/%&'"(136%(&+)1+:,%)%&%G%'("%)1+,,#)5#,5%&+3"%&#;)5(7+),#)-%-.(*$("%&#C)H#)5%5,(2$("%&#).):"#0#'#)1#)3&)%7$("'#&'%22%7()$"(G,+7#)1%)&+4"('(22%5%'I;)D3%&1%)$"%7#)1%)2(77%&2%'"#",#)%&):+&+"+)2%)#2$+''#)5<+)%,)"+&+)'"#$%#&'#'()#GG%#)"#::%3&'()3&)5+"'(),%0+,,()1%)43&6%(&#,%'I)"+&#,+8)

)

)

)

)

)

)

)

)

)

)

)

Tossicità da inibitori della calcineurina Reversibili Irreversibili

Sito d’azione Funzionali Strutturali Strutturali

Arteriola afferente GFR

Urea Pressione sanguigna

Vasocostrizione Danno endoteliale

Danno delle cellule muscolari lisce

Obliterazione dei vasi

Tubulo prossimale Alterazioni bioumorali K+

Mg

HCO3

Acido urico

Vacuoli

Mitocondri giganti

Microcalcificazioni

Atrofia

Fibrosi interstiziale

Page 124: sbobinature nefro_0 - SkyDrive

-&)'+7$%)$%F)"+5+&'%;):,%)%&%G%'("%)1%)7!L*;)5(7+)"#$#0%-%&#?)*%"(.%0>*?),A,"(.%0>*?)',0*%"(.%0>*;)<#&&()5(&2+&'%'()1%)#::%3&:+"+)#,)&(2'"()"+$+"'("%()4#"7#5%)7+&()&+4"('(22%5%)+)$%F)7#&+::+0(,%8)L::%;)%)1+"%0#'%)1+,,#)"#$#7%5%&#)2(&()3'%,%66#'%22%7%)%&)5,%&%5#8))

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

=,+%0,)@%)%&@>H%(&,W)

K 6("'%-(*',"(%@%)#@)#.',)@(*%)K G>"(&(0#L)B#&'%46:VI?):#-.%H>0#L?)5#*%.%/%0#L)B#&'%46:SXI)K 3!9)

=,+%0,)@%)0#&',&%0,&'(W)

K D&%L%'("%)@,..#)-#.-%&,>"%&#)K D&%L%'("%)@%)0!Y=)K 3&'%0,'#L(.%'%)A#6#'%($"%&#;)7(4+'%,K7%5(4+&(,#'(B)K Q',"(%@%)#)L#**,)@(*%)

a,%)25<+7%)'+"#$+3'%5%)0#"%#&()#)2+5(&1#)1+,,#)4#2+;)1+%)2+:&%)1%)"%:+''()+)1+,,+)2%&:(,+)2%'3#6%(&%8))

)

;"(L.,0#'%-J,)'"#$%#&'(.(+%-J,)

N)7(&'+)1+,)'"#$%#&'()+)1+,,#):+2'%(&+)1+,)$#6%+&'+)'"#$%#&'#'(;)0%).)3&),3&:()+)#553"#'(),#0("()5<+)2%)#"'%5(,#)4(&1#7+&'#,7+&'+)&+%)2+:3+&'%)$3&'%=)

#C U#.>'#H%(&,)@,.)"%-,A,&',)LC U#.>'#H%(&,)@,.)@(&#'(",)-C U#.>'#H%(&,)@,..Z("+#&(),*$%#&'#'()

!3''+)D3+2'+)$"(5+13"+)1+0(&()+22+"+)5(&1(''+)#,,/%&2+:&#)1+,,#)'"#2$#"+&6#)+)1+,)"%2$+''()1+,,/+'%5#)$+")D3#&'()"%:3#"1#)%,)$"(5+22()1%)#,,(5#6%(&+8))

f8 Z"(G,+7#'%5<+)"+,#'%0+)#,)1(&#'("+)

[,.)-#*()@,.)@(&#'(",)-#@#A,",;)%,)$"%7()$"(G,+7#)1#)#44"(&'#"+).),#)1+4%&%6%(&+)1+,,()2'#'()1%)7("'+;)3&)#":(7+&'()7(,'()%7$("'#&'+)%&)#7G%'()7+1%5(K,+:#,+8)H#),+::+)1+4%&%25+),#)7("'+)5(7+=)!"##$%&'(")&**"+"*#&,&-").&)/0//")-")$//&+&/1)."--2"(!"3$-'4)E3%&1%;)1#,)$3&'()1%)0%2'#)7+1%5(;)2'%#7()$#",#&1()1%)-,"A,..(?)'"(&-(),&-,E#.%-()+)0%@(..()*$%&#.,C))

Page 125: sbobinature nefro_0 - SkyDrive

S(7+)2%)0+1+)D3%)#)4%#&5(;)D3+2'%)5%&D3+)"%4,+22%)'"(&5(+&5+4#,%5%)1+0(&()+22+"+)%""+0+"2%G%,7+&'+)$+"2%=)

K *%4,+22()1%)#55(7(1#6%(&+)K *%4,+22()1%)#77%55#7+&'()K *%4,+22()1+,,#)'(22+)K Z+"1%'#)1+,)7(0%7+&'()(53,#"+)K Z+"1%'#)1+,)"%4,+22()1%)1%:"%:&#7+&'()

)

H#)7("'+)5+"+G"#,+;)%&(,'"+).)3&#)5(&1%6%(&+)5(&'"#11%2'%&'#)1#=)

K S(7#)$"(4(&1#)K N22+&6#)1%)"+2$%"()K 3**,&H#)@%)*(*'#&H,)@,$"%0,&'%)

-,&'"#.%)&,.)*#&+>,),)&,..,)>"%&,)K Z+"1%'#)1+%)"%4,+22%)'"(&5(+&5+4#,%5%)K 9()7(0%7+&'()A+55+''()"%4,+22%)'+&1%&+%)$"(4(&1%B)

J#,)$3&'()1%)0%2'#)7+1%5(K,+:#,+;)%&)-'#,%#),/#55+"'#7+&'()1+,,#)7("'+)5+"+G"#,+)1+0+)+22+"+)+44+''3#'()1#=)

K h&)7+1%5(),+:#,+)K h&)#&+2'+2%2'#)K h&)&+3"(,(:(_&+3"(5<%"3":()

-,)$+"%(1()1%)(22+"0#6%(&+)&+5+22#"%()$+")$('+")1+5"+'#"+),#)7("'+).)1%=)

K \)(",)$,")#@>.'%),)L#0L%&%)@%),'O)*>$,"%(",)#%)X)#&&%)K RS)(",)$,")L#0L%&%)'"#)R4X)#&&%)K S])(",)$,")%)L#0L%&%)@%),'O)%&E,"%(",)#)R)#&&()

-)'"+)7+1%5%)1+0(&()"%$+'+"+)+)-(&E,"0#",)%,)"%,%+0()2%73,'#&+()1%)'3''+),+)5(&1%6%(&%)5<+)#GG%#7()+,+&5#'()2($"#)#,,/%&%6%()1+,,/(22+"0#6%(&+;)#)7+'I)1+,,/(22+"0#6%(&+)+)#,,#)4%&+)1+,,/(22+"0#6%(&+8)-,)7(7+&'()1+,,#)7("'+)5(%&5%1+)5(&)D3+,,()1+,)$"%7()"%,%+0()1+,,#)$"+2+&6#)2%73,'#&+#)1+,,+)5(&1%6%(&%)2311+''+8))

IDONEITA’ DEL DONATORE

RIANIMAZIONE

Rianimatore/ Coordinatore

CRT/CIR

• Anamnesi • Esame Obiettivo • Esami di Laboratorio • Esami Strumentali

ANATOMIA PATOLOGICA

Istopatologo

• Oncologica

CENTRO TRAPIANTI

Nefrologo Chirurgo Istopatologo

• Idoneità / Non Idoneità

IDONEITA’ ORGANO

SALA OPERATORIA

Chirurgo

• Ispezione • Palpazione • Accertamento Autoptico

Page 126: sbobinature nefro_0 - SkyDrive

V+&:(&()5#'+:("%5#7+&'+)+25,32%)1#)D3#,2%#2%)'%$()1%)$"+,%+0()$#6%+&'%)5(&=)

! Q%,"($(*%'%A%'O)@#)1DUR)()S?)

! Q%,"($(*%'%A%'O)-(&',0$("#&,#)$,")15*3+),@)1:U?)

! [,($.#*%#)0#.%+&#)%&)#''()B'"#&&,)#.->&,)$",-%*,),--,H%(&%I?)

! D&E,H%(&%)*%*',0%-J,)*(*',&>',)@#)0%-"(("+#&%*0%)$,")%)F>#.%)&(&),*%*'(&()

($H%(&%)',"#$,>'%-J,)$"#'%-#L%.%?)0#.#''%,)@#)$"%(&%)#--,"'#',C)

)

[,($.#*%,)

H+)&+($,#2%+)5<+)&(&)+25,31(&()%,)'"#$%#&'()2(&(=)

K S#"5%&(7%)%&)2%'3)

K S#"5%&(7#)2$%&(5+,,3,#"+)53'#&+()&(&)7+'#2'#'%5()

K S#"5%&(7#)$#$%,,#"+)3"('+,%#,+)

K [#2#,%(7#)

-)'37("%)%&'"#5"#&%5%)2(&()3&)5#$%'(,()$#"'%5(,#"+=)#,53&%)&(&)+25,31(&(),#)1(&#6%(&+;)

#,'"%)"%5<%+1(&()3&#)0#,3'#6%(&+C)%&4%&+;)0+)&+)2(&()1%)$#"'%5(,#"%)5<+)+25,31(&(),#)

1(&#6%(&+)A7+13,,(G,#2'(7#)+1)#2'"(5%'(7#)#&#$,#2'%5(B8))

-,)5#"5%&(7#)$"(2'#'%5().)3&)#,'"()'37("+)5<+)%&)$#"'%5(,#"%)5(&1%6%(&%)$3@)5(&2+&'%"+)

5(73&D3+),#)1(&#6%(&+=)

)

))

)D&E,H%(&%)

H/%&4+6%(&+)1#)M-V)f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dK3$8))

CASI PARTICOLARI: IDONEITA’ DONATORE (II)

Altri Tumori:

• Carcinoma prostatico

Se valori superiori: -visita urologica -eco transrettale (se possibile) -esame istopatologico: 1) estemporaneo 2) definitivo 3) immunoistochimica

DONATORE PSA pos (>50aa) -PSA totale < 4 ng/ml -PSA totale / PSA libero < 10 ng/ml / > 25% SI Esame istopatologico: • Adenocarcinoma confinato all’interno della capsula con Gleason <4 in tutti i campioni: Rischio Standard

• Se uno o più campioni Gleason 4 e/o diffusione extracapsulare: Rischio aumentato ma accettabile

Page 127: sbobinature nefro_0 - SkyDrive

Z+"),/+$#'%'+)[)0#,+)3&)1%2("2()#&#,(:(;)7#),#)5(%&4+6%(&+)5(&)0%"32)MJV).)3&)5"%'+"%()1%)+25,32%(&+8)

)

)

)

))))))))))))