arf and glomerular filtrationedited

7/23/2019 ARF and Glomerular Filtrationedited

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Glomerular FiltrationGlomerular Filtration

andand Acute Renal Failure Acute Renal Failure

Eva Sian Li



Glomerular Filtration



Regulation of GF

The Renal System. Basic Science and Clinical Conditions. Churcill Livingstone. 2001

nder !hysiological conditions "alance "et#een the resistance in the afferent and

efferent arterioles



$easuring the GFR


% &nulin difiltrasi glomerulus' tida( mengalami rea"sor!si dan

se(resi

% )esulitan menentu(an C in inulin harus diinfus' sulit di!eri(sa



$easuring the GFR

% )reatinin *Cr+

, hasil meta"olisme (reatin *(om!onen otot s(elet+

, -umlah masa otot s(elet

, ifiltrasi

, Tida( mengalami rea"sor!si

, ise(resi(an minimal

% !ada gangguan fungsi gin/al




$easuring the GFR

% Creatinine *Cr+

, cr constant fo a

given individual under

steady state conditions

, Fied relationshi!

"et#een GFR and

!lasma creatinine' inthe form of rectangular

hy!er"ola




$easuring the GFR

% )reatinin *Cr+

, Cr !lasma ↑ "ila LFG

↓ 304

, Cr massa otot s(elet

% massa otot s(elet ↓

Cr !lasma 5 #alau!un

LFG ↓+




$easuring the GFR

% Rumus Coc(roft dan Gault

6er(iraan LFG *mL7 min+

180 , usia BB *(g+918 !lasma Cr *mmol7 L+

% !erem!uan 0'93




rea

% )urang "erma(na dalam menentu(an LFG% 6rodu( utama , hasil meta"olisme !rotein

, isintesis di hati ion amonium *(ata"olisme asamamino+:C;2

, 6rodu(si urea% /umlah !rotein yang dia"sor!si dari usus% (ece!atan (ata"olisme !rotein

% ifiltrasi "e"as di glomerulus

, 304 direa"sor!si% Fra(si urea filtrasi yang direa"sor"si tida( (onstan , Status hidrasi , La/u aliran urin

, (lirens urea : 304 LFG




Factors causing an increase in !lasma

creatinine and urea concentration


)reatinin rea

↓ LFG

↑ $assa otot s(elet */( !an/ang+

↓ LFG

↑ La/u aliran urin

↑ <su!an !rotein

iet

6erdarahan G&

↑ La/u (ata"oli( !rotein

Se!sisTera!i steroid

<nti"ioti( tetrasi(lin



Blood rea 5itrogen and Serum Creatinine

###.(idneyatlas.org



<cute renal failure *<RF+




% syndrome characteri=ed

, ra!id *hours to #ee(s+ decline in glomerular

filtration rate *GFR+

, retention of nitrogenous #aste !roducts such

as "lood urea nitrogen *B5+ and creatinine

% inde!endent ris( factor for mortality

% significant !rolongation in length of

hos!ital stay

Brenner Brenner > Rector?s The )idney' @th ed. Saunders. Alsevier. 2008

;ford Tet"oo( of Clinical 5e!hrology' rd Adition. ;ford niversity 6ress 2003




% *1+ renal hy!o!erfusion in #hich the integrity of

renal !arenchymal tissue is !reserved

, !rerenal a=otemia' !rerenal <RF 334 to D04+

% *2+ involving renal !arenchymal tissue , *intrarenal a=otemia' intrinsic renal <RF 34 to 804+

% *+ acute o"struction of the urinary tract

, *!ostrenal a=otemia' !ostrenal <RF E34+




Prerenal Azotemia

Major Causes of Prerenal Azotemia

Intravascular Volume Depletion% emorrhage traumatic' surgical' gastrointestinal' !ost!artum% Gastrointestinal losses vomiting' nasogastric suction' diarrhea% Renal losses druginduced or osmotic diuresis' dia"etes insi!idus' adrenal insufficiency% S(in and mucous mem"rane losses "urns' hy!erthermia' other causes of increased insensi"le

losses

% HThirds!aceH losses !ancreatitis' crush syndrome' hy!oal"uminemiaDecreased Cardiac Output% iseases of myocardium' valves' !ericardium' or conducting system% 6ulmonary hy!ertension' !ulmonary em"olism' !ositive!ressure mechanical ventilation% Systemic vasodilatation% rugs antihy!ertensives' afterload reduction' anesthetics' drug overdoses% Se!sis' liver failure' ana!hylais

Renal Vasoconstriction% 5ore!ine!hrine' ergotamine' liver disease' se!sis' hy!ercalcemia

Pharmacologic Agents That Acutel Impair Autoregulation and !lomerular "iltration Rate in#pecific #ettings

% <ngiotensinconverting en=yme inhi"itors in renal artery stenosis or severe renal hy!o!erfusion% &nhi"ition of !rostaglandin synthesis "y nonsteroidal antiinflammatory drugs during renal

hy!o!erfusion




Intrinsic Renal Azotemia

Major Causes of Acute Intrinsic Renal Azotemia

Diseases Involving $arge Renal Vessels % Renal arteries throm"osis' atheroem"olism' throm"oem"olism' dissection' vasculitis *e.g.'

Ta(ayasu+% Renal veins throm"osis' com!ression

Diseases of !lomeruli and the Renal Microvasculature% &nflammatory acute or ra!idly !rogressive glomerulone!hritis' vasculitis' allograft re/ection'

radiation% asos!astic malignant hy!ertension' toemia of !regnancy' scleroderma' hy!ercalcemia' drugs'radiocontrast agents

% ematologic hemolyticuremic syndrome or throm"otic throm"ocyto!enic !ur!ura' disseminatedintravascular coagulation' hy!erviscosity syndromes

Diseases Characterized % Prominent Injur to Renal Tu%ules Often &ith Acute Tu%ule 'ecrosis% &schemia caused "y renal hy!o!erfusion% Aogenous toins *e.g.' anti"iotics' anticancer agents' radiocontrast agents' !oisons

% Andogenous toins *e.g.' myoglo"in' hemoglo"in' myeloma light chains' uric acid' tumor lysisAcute Diseases of the Tu%ulointerstitium% <llergic interstitial ne!hritis *e.g.' anti"iotics' nonsteroidal antiinflammatory drugs+% &nfectious *viral' "acterial' fungal+% <cute cellular allograft re/ection% &nfiltration I *e.g.' lym!homa' leu(emia' sarcoid+




Postrenal Azotemia

Causes of Acute Postrenal Azotemia

(reteric O%struction% &ntraluminal stones' "lood clot' sloughed renal !a!illae' uric acid or

sulfonamide crystals' fungus "alls% &ntramural !osto!erative edema after ureteric surgery' B) virus

induced ureteric fi"rosis in renal allograft% Atraureteric iatrogenic *ligation during !elvic surgery+% 6eriureteric hemorrhage' tumor' or fi"rosis

)ladder 'ec* O%struction% &ntraluminal stones' "lood clots' sloughed !a!illae

% &ntramural "ladder carcinoma' "ladder infection #ith mural edema'neurogenic' drugs *e.g.' tricyclic antide!ressants' ganglion "loc(ers+% Atramural !rostatic hy!ertro!hy' !rostatic carcinoma

(rethral O%struction% 6himosis' congenital valves' stricture' tumor




6hases of <cute Tu"ule 5ecrosis

% initiation !hase , hy!othetical !eriod of time during #hich renal

!erfusion is com!romised to the etent that it!reci!itates a com!le array of intrarenal events that

are res!onsi"le for !ersistence of renal dysfunctionlong after the initiating cause has "een resolved

% maintenance !hase , !eriod of ongoing renal failure *lasting days to #ee(s+

that follo#s the initiation !hase.

% recovery !hase , renal in/ury is re!aired and relatively normal or

"aseline renal function is reesta"lished




Pathophsiolog of Acute Tu%ule

'ecrosis *<T5+




Acute Tu%ule 'ecrosis in #epsis




ConseJuences of <cute Tu"ule &n/ury

5ecrosis' <!o!tosis' and Su"lethal &n/ury




Common Com!lications of <RF




Clinical a!!roach to the !atient #ithacute renal failure



6eng(a/ian

% Acute Kidney Injury , An abrupt (within 48 h) reduction in kidney function defined as

an absolute increase in serum creatinine level of ≥ !"4 #mol$l(%"& m'$dl)

, a percenta'e increase in serum creatinine level of ≥*%+ (,"*-

fold from baseline)

, a reduction in urine output (documented oli'uria of .%"* ml$k'$h

for /! h)

5at Clin 6ract 5e!hrol. 200@*9+8K882



6eng(a/ian

5at Clin 6ract 5e!hrol. 200@*9+8K882



Categories of renal failure




rinary diagnostic indices in acute

renal failure *<RF+



rinalysis in acute renal failure

*<RF+



$<5<GA$A5T ;F <CTARA5<L F<&LRA



Prerenal Azotemia

% Ra!idly reversi"le on restoration of renal!erfusion

% The com!osition of re!lacement fluids fortreatment of hy!ovolemia varies de!ending onthe source of fluid loss.

% Serum ): concentration and acid"ase statusshould "e monitored in all su"/ects




Prerenal Azotemia

Cardiac Failure

% Cardiac failure may reJuire aggressive

management #ith loo! diuretics' antiarrhythmic

drugs' !ositive inotro!es' !reload and7or

afterloadreducing agents' and mechanical aidssuch as an intraaortic "alloon !um!.

% &nvasive hemodynamic monitoring is invalua"le

for guiding thera!y in com!licated cases in

#hich clinical assessment of cardiovascularfunction and intravascular volume may "e

difficult and unrelia"le.




Intrinsic Renal Azotemia +

6revention

% ;!timi=ation of cardiovascular function and

intravascular volume is the single most

im!ortant maneuver in the management of acute

intrinsic a=otemia.% Contrast ne!hro!athy

, 6ro!hylactic infusion of halfnormal saline

% 1 mL7(g for 12 hours "efore and after !rocedure

, 6ro!hylactic administration of oral acetylcysteine% D00 mg t#ice daily' 28 hours "efore and 28 hours after the

!rocedure





6revention

% iuretics' 5S<&s *including C;2 inhi"itors+' <CA inhi"itors' and other vasodilators should "eused #ith caution in !atients #ith sus!ected trueor effective hy!ovolemia or renovasculardisease' "ecause they may convert !rerenala=otemia to ischemic <T5 and sensiti=e the!atients to the actions of ne!hrotoins

% Careful monitoring of circulating drug levelsa!!ears to reduce the incidence of <RFassociated #ith aminoglycoside anti"iotics orcalcineurin inhi"itors





6revention

% <llo!urinol is useful for limiting uric acidgeneration in !atients at high ris( for acute uratene!hro!athy

% <mifostine' an organic thio!hos!hate' has "eendemonstrated to ameliorate cis!latinne!hrotoicity in !atients #ith solid organ orhematologic malignancies

% Forced diuresis and al(alini=ation of urine mayattenuate renal in/ury caused "y uric acid ormethotreate and after rha"domyolysis





6revention

% 5<cetylcysteine limits acetamino!heninduced

renal in/ury if given #ithin 28 hours of ingestion'

% imerca!rol' a chelating agent' may !revent

heavy metal ne!hrotoicity% Athanol inhi"its ethylene glycol meta"olism to

oalic acid and other toic meta"olites and is an

im!ortant ad/unct to hemodialysis in the

emergency management of this intoication





% HRenal dose do!amineH *1 to mg7(g7min+ , #idely advocated for the management of oliguric <RF

, has not "een demonstrated to !revent or alter thecourse of ischemic or ne!hrotoic <T5

, lac( of efficacy

, do!amine' even at lo# doses' is !otentially toic incritically ill !atients and can induce tachyarrhythmiasand myocardial ischemia among other com!lications.

% routine administration of do!amine to !atients#ith oliguric <RF is not /ustified "ased on the"alance of e!erimental and clinical evidence





% <56 *<trial 5atriuretic 6e!tide+

, augments GFR "y triggering afferent arteriolar

vasodilatation and increasing ultrafiltration coefficient

*)f+

, inhi"its sodium trans!ort and lo#ers oygen

reJuirements in several ne!hron segments

, Synthetic analogs of <56 have sho#n !romise in the

management of <T5 in the la"oratory setting.

% has failed to translate into clinically a!!arent "enefit





% The administration of highdoseintravenous diuretics to individuals #itholiguric <RF

, commonly !racticed , may minimi=e fluid overload

, no evidence that it alters the mortality rate orthe dialysisfree survival rate.

, increased ris( of death and nonrecovery ofrenal function in !atients treated in thismanner





% <RF caused "y other intrinsic renaldiseases' such as acuteglomerulone!hritis or vasculitis' may

res!ond to corticosteroids' al(ylatingagents' and7or !lasma!heresis'de!ending on the !rimary disease.

% Corticosteroids a!!ear to hastenremission in some cases of allergicinterstitial ne!hritis





% 6lasma echange and !lasma infusion are

useful in the treatment of s!oradic and

familial forms of S and TT6

% 6ostdiarrheal S in children is usually

managed conservatively' and evidence

eists to suggest that early anti"iotic

thera!y may actually !romote thedevelo!ment of S





% 6lasma!heresis may also "e of "enefit in <RF

caused "y myeloma cast ne!hro!athy

% Clearance of circulating light chains #ith

concomitant chemothera!y to decrease the rateof !roduction sho#ed !romise in reversing renal

in/ury in !atients #ith circulating light chains'

heavy Bence -ones !roteinuria' and <RF in a

single !ros!ective study





% <ggressive control of systemic arterial

!ressure is of !aramount im!ortance for

limiting renal in/ury in malignant

hy!ertensive ne!hrosclerosis' and othervascular diseases

% y!ertension and <RF associated #ith

scleroderma may "e eJuisitely sensitiveto treatment #ith <CA inhi"itors.





$anagement of Com!lications

% &ntravascular volume overload can usually "emanaged "y restriction of salt and #ater inta(eand the use of diuretics

% no !roven rationale for routine administration of

diuretics to !atients #ith <RF other than to treatthis com!lication

% &n the volumeoverloaded !atient , high doses of loo! diuretics such as furosemide

*"olus doses of u! to 200 mg or u! to 20 mg7hour asan intravenous infusion+ or seJuential thia=ide andloo! diuretic administration may "e reJuired if there isno res!onse to conventional doses.





$anagement of Com!lications% iuretic thera!y should "e discontinued in resistant

!atients to avoid com!lications such as ototoicity.

% ltrafiltration or dialysis may "e reJuired for removal ofvolume if conservative measures fail.

% y!onatremia associated #ith a fall in effective serumosmolality can usually "e corrected "y restriction of#ater inta(e.

% y!ernatremia is treated "y administration of #ater'hy!otonic saline solutions' or hy!otonic detrosecontaining solutions *the latter are effectively hy!otonic"ecause detrose is ra!idly meta"oli=ed+






% $ild hy!er(alemia *E3.3 mAJ7L+ , initially "y restriction of dietary !otassium inta(e , elimination of ) su!!lements and )s!aring diuretics.

% $oderate hy!er(alemia *3.3 to D.3 mAJ7L+ in!atients #ithout clinical or ACG evidence ofhy!er(alemia , administration of ):"inding ion echange resins

such as sodium !olystyrene sulfonate *13 to 0 gevery or 8 hours+ #ith sor"itol *30 to 100 mL of 204solution+ "y mouth or as a retention enema.

, Loo! diuretics also increase ): ecretion in diureticres!onsive !atients.






% serum ): values greater than D.3 mAJ7L% ACG a"normalities or clinical features of

hy!er(alemia , Amergency measures

, &ntravenous insulin% *10 of regular insulin+ and glucose *30 mL of 304

detrose+% !romote ): shift into cells #ithin 0 to D0 minutes% lasts for several hours.

, Sodium "icar"onate% *1 am!ule' 88.D mAJ intravenously over 3 minutes+% !romotes ra!id shift of ): into the intracellular s!ace *onset

less than 13 minutes' duration 1 to 2 hours+


I i i R l A i





% &ntravenous al"uterol *0.3 mg in 100 mL of 34detrose over 3 minutes+ or ne"uli=ed al"uterol*10,20 mg+.

%Calcium solutions calcium gluconate , *10 mL of 104 solution intravenously over 3 minutes+

, antagoni=e the cardiac and neuromuscular effects ofhy!er(alemia and !rovide a valua"le emergencytem!ori=ing measure #hile other agents reduce the

serum ): concentration.

% ialysis is indicated if hy!er(alemia is resistantto these measures.


I t i i R l A t i





% $eta"olic acidosis does not reJuire treatmentunless the serum C; concentration falls"elo# 13 mAJ7L.

% $ore severe acidosis can "e corrected "y either

oral or intravenous "icar"onate administration.% should "e monitored for com!lications of

"icar"onate administration' including meta"olical(alosis' hy!ocalcemia' hy!o(alemia' volume

overload' and !ulmonary edema.


I t i i R l A t i





% y!er!hos!hatemia , usually "e controlled "y restriction of dietary !hos!hate

inta(e and oral administration of agents *e.g.' aluminumhydroide' calcium car"onate' sevelamer+ that reducea"sor!tion of 6;8 from the gastrointestinal tract.

% y!ocalcemia , does not usually reJuire treatment unless it is severe'

as may occur in !atients #ith rha"domyolysis or!ancreatitis or after administration of "icar"onate.

% y!eruricemia , usually mild in <RF *E13 mg7dL+ , does not reJuire s!ecific intervention.


I t i i R l A t i





% individuali=ed nutritional management is

reJuired' es!ecially for critically ill !atients

receiving renal re!lacement thera!y' in #hom

!rotein cata"olic rates can eceed 1.3 g7(g "ody#eight !er day

% The o"/ective of dietary modification in <RF is to

!rovide sufficient calories to !reserve lean "ody

mass' avoid starvation (etoacidosis' and!romote healing and tissue re!air' #hile

minimi=ing the !roduction of nitrogenous #aste.


I t i i R l A t i





% &f the duration of renal insufficiency is li(ely to "eshort and the !atient is not cata"olic' thendietary !rotein should "e restricted to less than0.9 g7(g "ody #eight !er day

% Cata"olic !atients' including those receivingcontinuous renal re!lacement thera!y' mayreceive u! to 1.8 mg7(g "ody #eight !er day

% Total caloric inta(e should not eceed 3 (cal7(g"ody #eight !er day and #ill ty!ically range from23 to 0 (cal7(g "ody #eight !er day


I t i i R l A t i





% The enteral route of nutrition is !referred'"ecause it avoids the mor"idity associated #ith!arenteral nutrition #hile !roviding su!!ort tointestinal function

% Matersolu"le vitamin su!!lementation isadvised' #ith the ece!tion of vitamin C' #hichcan' in high doses *E200 mg7day+' !romoteurinary oalate ecretion and stone formation


I t i i R l A t i




$anagement of Com!lications% <nemia may necessitate "lood transfusion or the

administration of recom"inant human erythro!oietin if it issevere or if recovery is delayed.

% remic "leeding usually res!onds to desmo!ressin'correction of anemia' estrogens' or dialysis.

% oses of drugs that are ecreted "y the (idney must "ead/usted for the degree of renal im!airment.

% Gastric stress ulcer !ro!hylais is not indicated unless the!atient is intu"ated or has a concurrent coagulo!athy

% Fe"rile !atients must "e investigated aggressively forinfection and may reJuire treatment #ith "roads!ectrumanti"iotics #hile a#aiting identification of s!ecificorganisms.


I t i i R l A t i




&ndications and $odalities of ialysis

% ialysis does not hasten recovery from <RF.

% Aarly and unnecessary hemodialysis may

!otentially eacer"ate renal hy!o!erfusion'

"ecause transient hy!otension is a commoncom!lication of this treatment modality' and

leu(ocytes activated on e!osure to dialysis

mem"ranes may !otentially aggravate ischemic

renal in/ury


I t i i R l A t i




&ndications and $odalities of ialysis

% There is no firm consensus on the initiation ofdialysis in <RF.

% <"solute indications for the commencement ofrenal re!lacement thera!y include

, sym!tomatic uremia *asteriis' !ericardial ru"'ence!halo!athy+ and acidosis' hy!er(alemia' orvolume overload that !roves refractory to medicalmanagement.

% The choice of dialysis modality *!eritoneal

dialysis' hemodialysis' or hemofiltration+ , resources of the health care institution' the technical

e!ertise of the !hysician' and the clinical status of the!atient.




Postrenal Azotemia

% rethral or "ladder nec( o"struction is usuallyrelieved tem!orarily "y transurethral orsu!ra!u"ic !lacement of a "ladder catheter'

% reteric o"struction may "e treated initially "y

!ercutaneous catheteri=ation of the dilatedureteric !elvis or ureter

% ;"structing lesions can often "e removed

!ercutaneously

% $ost !atients e!erience an a!!ro!riate diuresis

for several days after relief of o"struction




Than* ,ou

arf and glomerular filtrationedited

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