RENAL DISEASESRENAL DISEASES

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WELCOME

ALL 66

At the end… you will learnAt the end… you will learn

• Kidney disease can be Kidney disease can be a a silent killersilent killer• Childhood NS is mostly curableChildhood NS is mostly curable• APSGN mostly recoversAPSGN mostly recovers; ; does nor recurdoes nor recur• HematuriaHematuria in small children is usually harmless in small children is usually harmless• With ageing most of us develop kidney diseaseWith ageing most of us develop kidney disease• ARF in most cases can be preventedARF in most cases can be prevented

APSGN: ac. Post-strep. Glomerulonephritis. ARF: ac. Renal failureAPSGN: ac. Post-strep. Glomerulonephritis. ARF: ac. Renal failure

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Summary: Renal Function

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Importance of kidneyImportance of kidney

• Main Main waste excreterwaste excreter• Maintains Maintains fluid-, electrolyte- & ABBfluid-, electrolyte- & ABB• Makes Makes erythropoietin, thrombopoietinerythropoietin, thrombopoietin• Excretes some Excretes some drugsdrugs• Biotransforms/activates Biotransforms/activates VDVD

ABB: acid base balanceABB: acid base balance

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Peculiarities of Kidney DiseasesPeculiarities of Kidney Diseases

• May be asymptomatic May be asymptomatic • Symptoms can be Symptoms can be nonspecific nonspecific • Few physical signsFew physical signs• May present with May present with jaundice jaundice in infantsin infants• Important c/of Important c/of FTTFTT• Long UT means more Long UT means more obstructionobstruction

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Micros. H:Micros. H: in a well child: ~ in a well child: ~ no testno test if not x3/over several mo.; if not x3/over several mo.; evaluate if HTN, CKD, evaluate if HTN, CKD,

casturia/proteinuria presentcasturia/proteinuria presentGross H: Gross H: urine is red/tea/cola urine is red/tea/cola

colored. It is also mostly colored. It is also mostly benignbenign

Up to 5 RBC/HPF in urine is Up to 5 RBC/HPF in urine is normal in childrennormal in children

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Causes:Causes:GH is more in boys. GH is more in boys.

Assess by CF. Assess by CF.

VCUG is useful in VCUG is useful in

doubtful USG, UTI, doubtful USG, UTI,

or voiding problem. or voiding problem.

Cystoscopy if Cystoscopy if

persistent or with persistent or with

ambiguous imagingambiguous imagingGH: gross hematuria. VCUG : voiding GH: gross hematuria. VCUG : voiding

cystourethrographycystourethrography

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: ABCDEFGHI: ABCDEFGHI

Henoch-Schonlein purpuraHenoch-Schonlein purpura• Classic triad: Classic triad: purpurapurpura (100%), (100%), arthritis/j. pain arthritis/j. pain (80%), (80%), AP (AP (60%)60%)• 70% affect kidneys (hematuria)70% affect kidneys (hematuria)• Histologically vasculitis, Histologically vasculitis, IgANIgAN• May relapseMay relapse• Severe: steroids, azathioprineSevere: steroids, azathioprine• Follow until urinalysis normalFollow until urinalysis normal• 5-20% of children end in ESRD5-20% of children end in ESRD

IgAN: IgA nephropathy. ESRD: end stage renal diseaseIgAN: IgA nephropathy. ESRD: end stage renal disease

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Purpuras Purpuras ((necrotizing necrotizing vasculitis in dermal vasculitis in dermal small small BV; usually BV; usually extensor extensor surfaces of surfaces of limbs, limbs, sometimes sometimes buttocksbuttocks

AP, V, gut bleedingAP, V, gut bleeding: : vasculitis in GITvasculitis in GIT

Renal: Renal: commonest is commonest is hematuria. In adults: hematuria. In adults: it is it is more severe & more severe & may may evolve into a evolve into a rapidly rapidly progressive, progressive, crescentic GNcrescentic GN

A Case HistoryA Case History

• A 12y-boy has hematuria. He has occasional dark A 12y-boy has hematuria. He has occasional dark urine after heavy exercise but not GHurine after heavy exercise but not GH

• No h/o medicine, deafness; no FH of renal d.No h/o medicine, deafness; no FH of renal d.• PE: PE: normal: normal: BP 130/80BP 130/80• Trace proteinuriaTrace proteinuria• 10-15 rbc/hpf. No casts10-15 rbc/hpf. No casts

• What is the most probable Dx?What is the most probable Dx?

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Answer: Exercise Induced HematuriaAnswer: Exercise Induced Hematuria

• Hematuria: asymptomaticHematuria: asymptomatic• 5-10% in the community5-10% in the community• No features of NS/GNNo features of NS/GN

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Renal Function in NewbornRenal Function in Newborn

GFRGFR

– 5ml/min in first week of life5ml/min in first week of life– 10ml/min 1-2 mo10ml/min 1-2 mo– Preterm has lower GFRPreterm has lower GFR

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TerminologiesTerminologies

• Black water F: Black water F: (malaria (malaria hemolysishemolysis: : hemoglobinuriahemoglobinuria))• CKD/CRF: CKD/CRF: progressive RF over 3mo (Dm, HTN, GN)progressive RF over 3mo (Dm, HTN, GN)

• GN: GN: glomeruli & tubules inflamedglomeruli & tubules inflamed• Mesangium: Mesangium: cells supporting glomeruli: cells supporting glomeruli: phagocyticphagocytic• ARF: ARF: Ac. Renal Failure Ac. Renal Failure

(hours-days)(hours-days)

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• ESRD: ESRD: Total CRF (GFR <15ml). Rx: Total CRF (GFR <15ml). Rx: dialysis/transplant dialysis/transplant

(renal replacement therapy)(renal replacement therapy)

• ATN:ATN: Ac. kidney Injury: severe ARF (severe infx./ Ac. kidney Injury: severe ARF (severe infx./ hypotension). May need dialysishypotension). May need dialysis. “. “Muddy brown casts" Muddy brown casts" (epith. cells) is (epith. cells) is pathognomonicpathognomonic

• ESWLESWL (Extracorporeal Shockwave Lithotripsy):(Extracorporeal Shockwave Lithotripsy): to break to break kidney stoneskidney stones

2626ESRD: end stage renal disease. ATN: ac. Tubular necrosis

ATN: muddy brown casts

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• HUS:HUS: destroys destroys lininglining of BV & RBCof BV & RBC; often c/by ; often c/by E. coliE. coli; ; may get ARF or coagulopathymay get ARF or coagulopathy

• Alport Syn.:Alport Syn.: inherited. Hematuria, proteinuria. More inherited. Hematuria, proteinuria. More serious in boys; leads to ESRD, hearing & visual lossserious in boys; leads to ESRD, hearing & visual loss

• PKD:PKD: inherited, AD: grape-like cysts in kidneys; destroy inherited, AD: grape-like cysts in kidneys; destroy kidneys: CKD & ESRDkidneys: CKD & ESRD

HUS: hemolytic uremic syn. PKD: polycystic kidney DHUS: hemolytic uremic syn. PKD: polycystic kidney D

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• Interstitial Nephritis: Interstitial Nephritis: Inflam. of supporting tissue of Inflam. of supporting tissue of kidney; can lead to ARF/ESRDkidney; can lead to ARF/ESRD

• Renal osteodystrophy: Renal osteodystrophy: RF causing weak bones; RF causing weak bones; more in dialysis pts.: high PO4/low VDmore in dialysis pts.: high PO4/low VD

• RTA:RTA: kidneys fail to remove acids normally: weak bones, kidneys fail to remove acids normally: weak bones, kidney stones & FTTkidney stones & FTT

RTA: renal tubular acidosisRTA: renal tubular acidosis

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Acute Kidney InjuryAcute Kidney Injury ( (AKIAKI) () (ARFARF))abrupt loss of RF within 7d. Renal damage is due to low BF abrupt loss of RF within 7d. Renal damage is due to low BF

(low BP), renotoxins, inflam., or obs. of UT(low BP), renotoxins, inflam., or obs. of UT• Dx.: Dx.: typical lab.: raised BUN & creatinine, or low UOPtypical lab.: raised BUN & creatinine, or low UOP• Complications: Complications: m. acidosis, high K+, uremia, FE imbalance, m. acidosis, high K+, uremia, FE imbalance,

& effects on other systems, death. More risk of CKD& effects on other systems, death. More risk of CKD• Causes Causes are numerous. Commonare numerous. Common

– Severe Severe dehydration, sdehydration, shock, ac. hock, ac. hgehge– BlockageBlockage of renal BV, of renal BV, obstructionobstruction in UT in UT– Renal Renal injuryinjury– Ac. Ac. GN, aGN, acc. PN. PN

• Rx.: underlying cause & supportive like RRTRx.: underlying cause & supportive like RRT

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CKD (CRF): CKD (CRF): GFR <90ml/min/1.73mGFR <90ml/min/1.73m2 2 >3 mo>3 mo

5 stages5 stages• GFR 90ml/min/1.73m2 GFR 90ml/min/1.73m2 NormalNormal• 60-89 ….60-89 …. MildMild• 30-59 ….30-59 …. ModerateModerate• 15-29 ….15-29 …. SevereSevere• <15/dialysis <15/dialysis ESRDESRD

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Causes of CKDCauses of CKD

• Primary: Primary: FSGS, MGN, MPGNFSGS, MGN, MPGN, crescentic GN, , crescentic GN, Goodpasture syn.Goodpasture syn.

• Systemic: Systemic: DM, HTN, SLE, HSP, IgAN, APSGN, HIV, HBV, HCVDM, HTN, SLE, HSP, IgAN, APSGN, HIV, HBV, HCV

• Vascular: Vascular: Nephrosclerosis, ANCA, HUSNephrosclerosis, ANCA, HUS

• Hereditary: Hereditary: Amyloidosis, PKD, Alport syn.Amyloidosis, PKD, Alport syn.

• Tubulointerstitial: Tubulointerstitial: drugs/toxins, VUR, obs. uropathydrugs/toxins, VUR, obs. uropathy

ANCAs: Anti-neutrophil cytoplasmic AbANCAs: Anti-neutrophil cytoplasmic Ab: : mainly IgG, against neutrophil & monocyte mainly IgG, against neutrophil & monocyte cytoplasm. Seen in some AID. Particularly associated with systemic vasculitis (ANCA cytoplasm. Seen in some AID. Particularly associated with systemic vasculitis (ANCA vasculitides)vasculitides)

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Urea frost in CRF

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Goodpasture Syn. Goodpasture Syn. ((anti-GBM d.)anti-GBM d.)• AID: pulmo-renal syn.: anti-collagen Ab in lungs: AID: pulmo-renal syn.: anti-collagen Ab in lungs: vasculitis: vasculitis:

hge., kidneys: hge., kidneys: GN (anti-GBM Abs)GN (anti-GBM Abs)• It is It is fatalfatal unless quickly Rxunless quickly Rx..

IgA NephropathyIgA Nephropathy ((Berger DBerger D): ): RF is rareRF is rare

• Commonest GN in WestCommonest GN in West. . IgA deposits after URTI: silent IgA deposits after URTI: silent hematuria; may go for yrshematuria; may go for yrs

• Men more. All ages Men more. All ages • No Rx if early/mild with normal BP & <1g 24TUP: if more, No Rx if early/mild with normal BP & <1g 24TUP: if more,

Rx. with ACEI or ARBsRx. with ACEI or ARBs

AID: autoim. d. GBM: glomerular basement membrane. RF: renal failure. TUP: total urinary proteinAID: autoim. d. GBM: glomerular basement membrane. RF: renal failure. TUP: total urinary protein

Paroxysmal Noc. Hb.uria (PNH)Paroxysmal Noc. Hb.uria (PNH)

Rare. Rare. Acquired. Life-threatening d. characterized Acquired. Life-threatening d. characterized by by complement-induced IV hemolysiscomplement-induced IV hemolysis

• Some proteins cannot fix to RBCs CW to protect them from Some proteins cannot fix to RBCs CW to protect them from complements: hemolysis: Hb.emia & Hb.uria; at complements: hemolysis: Hb.emia & Hb.uria; at

night/early morningnight/early morning• Any age. May cause Any age. May cause aplastic a., AML, MDSaplastic a., AML, MDS

• SS: SS: RAP, backache, HA, SoB, clotting; dark urine; easy RAP, backache, HA, SoB, clotting; dark urine; easy bruisingbruising

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MDS: MDS: myelodysplastic syn. CW: cell wall. SoB: short of breathingmyelodysplastic syn. CW: cell wall. SoB: short of breathing

Investigations for PNHInvestigations for PNH

• Pancytopenia, Pancytopenia, Hb.emia & hb.uriaHb.emia & hb.uria• Coombs' test; haptoglobin levelCoombs' test; haptoglobin level• Flow cytometry to measure certain proteinsFlow cytometry to measure certain proteins• Ham (acid hemolysin) testHam (acid hemolysin) test• Sucrose hemolysis testSucrose hemolysis test• Urine hemosiderinUrine hemosiderin

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Rx for PNHRx for PNH• Steroids/immunosuppressantsSteroids/immunosuppressants• BT. Iron & B9. Blood thinnersBT. Iron & B9. Blood thinners• EculizumabEculizumab can block hemolysiscan block hemolysis• BMT can cureBMT can cure• Vaccinations against certain types of bacteriaVaccinations against certain types of bacteria

Outlook: Outlook: most people survive >10 y after Dx. Death occur most people survive >10 y after Dx. Death occur from thrombosis or bleedingfrom thrombosis or bleeding

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Ac Nephritic Ac Nephritic (Glomerulonephritic) (Glomerulonephritic) Syn.Syn.• Ac. inflam. of the glomeruli & nephronsAc. inflam. of the glomeruli & nephrons

Nephrotic SyndromeNephrotic Syndrome• Affection of nephrons with leakage of protein (usually Affection of nephrons with leakage of protein (usually

nono inflam.) inflam.)

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GlomerulonephritisGlomerulonephritis• Inflam. & proliferation of Glomerular tissue with damage to Inflam. & proliferation of Glomerular tissue with damage to

BM, mesangium/capillary endotheliumBM, mesangium/capillary endothelium

• Acute: Acute: hematuria, proteinuria & RBC casts. Often with HTN, hematuria, proteinuria & RBC casts. Often with HTN, edema & impaired RFedema & impaired RF

• ChronicChronic: above with scarring of nephrons & progressive RF: above with scarring of nephrons & progressive RF

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Ac Nephritis: causesAc Nephritis: causes

– Group A Streptococcus Group A Streptococcus 80%80%

– OthersOthers 20%20%• Systemic: Systemic: HSP, HSP, SLE, IgAN,SLE, IgAN, Goodpasture, gold, Goodpasture, gold,

penicillaminepenicillamine• Infx.: Infx.: staph, pneumococci, Gram-ve, malaria, HBV, staph, pneumococci, Gram-ve, malaria, HBV,

HCV, MMR, HIVHCV, MMR, HIV• Infective endocarditisInfective endocarditis• Renal d: Renal d: MGN, MPGN, FSGS, etc.MGN, MPGN, FSGS, etc.

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A.P.S.G.N.A.P.S.G.N.• 15% of all GAS infx.; mostly RTI (skin 10%)15% of all GAS infx.; mostly RTI (skin 10%)• Lag period: 2-3wLag period: 2-3w• 2% clinically overt2% clinically overt• No recurrenceNo recurrence• Any Age Any Age (2-15y; 2% <2y; 10% >40y)(2-15y; 2% <2y; 10% >40y)• Boys moreBoys more• Excellent prognosisExcellent prognosis: : <2% MR. 2% Chr. GN<2% MR. 2% Chr. GN• Cerebral vasculitis may occurCerebral vasculitis may occur

GAS: group A streptococciGAS: group A streptococci

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PathophysiologyPathophysiology Exact mechanism is unclearExact mechanism is unclear Autoim. d: Autoim. d: both CMI & humoral. both CMI & humoral. Immune complex Immune complex deposits in deposits in

glomeruli, activates complement: inflam.glomeruli, activates complement: inflam.

Strep. itself Strep. itself does not attack the kidneydoes not attack the kidney Kidneys may enlarge ~50%Kidneys may enlarge ~50% Histology: Histology: swelling of glomeruli, polymorphs infiltrateswelling of glomeruli, polymorphs infiltrate

IF: IF: deposition of Ig & complementdeposition of Ig & complement

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CFCF of APSGN of APSGN

Acute: Acute: H/o earlier URTI, skin infx. a few weeks beforeH/o earlier URTI, skin infx. a few weeks before Puffy face, scanty HC/Puffy face, scanty HC/coca colored coca colored urineurine Flank pain (stretching of renal capsule)Flank pain (stretching of renal capsule) Weakness, -/+ AP, anorexia, FWeakness, -/+ AP, anorexia, F Anasarca, SoB/Anasarca, SoB/exertional dyspnoea, exertional dyspnoea, coughcough HTN, HA, LVF, convulsionHTN, HA, LVF, convulsion Hematuria (universal)Hematuria (universal)

HC: high coloredHC: high colored

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Lab InvestigationsLab Investigations

• UrineUrine: : RBCs, RBC casts, WBC, +/++ proteinRBCs, RBC casts, WBC, +/++ protein• FBC: FBC: dilutional anemia, leucocytosisdilutional anemia, leucocytosis• Evidence of recent strep. infEvidence of recent strep. inf.: ASO titer, .: ASO titer, Anti-Dnase B, Anti-Dnase B,

throat/wound CSthroat/wound CS• ?Elevated urea ?Elevated urea ±± creatinine creatinine• Low complement C3Low complement C3

Anti-Dnase B: Ab made against GAS. Raised levels indicate: Rh. F, PSGN, Strep. throat or Strep. skin infection

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Renal BiopsyRenal Biopsy

• Declining Renal FunctionDeclining Renal Function• Atypical presentationAtypical presentation• F/history of renal DF/history of renal D• Persistent HTN or gross hematuria Persistent HTN or gross hematuria • HypocomplementemiaHypocomplementemia

Hallmark in PSGN Hallmark in PSGN is subepithelial ‘humps’ representing is subepithelial ‘humps’ representing immune complex depositionimmune complex deposition

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DiagnosisDiagnosis

• CF, swab CS, positive ASO and/or anti-DNase BCF, swab CS, positive ASO and/or anti-DNase B• C3 is typically low (normalizes 6- 12w). But normal C3 is typically low (normalizes 6- 12w). But normal

C3 does not exclude itC3 does not exclude it

DDDD• IgANIgAN• HSP, SLEHSP, SLE• HUS, other inf.HUS, other inf.

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Rx Of APSGNRx Of APSGNMainly supportive. Mainly supportive. Bed restBed rest

• Fluid & salt restriction. Fluid & salt restriction. FEBFEB• Rx of hyperkalemia. Rx of hyperkalemia. No fruits!No fruits!• Penicillin x 10d: why?Penicillin x 10d: why?• BP control. ACEI can cause hyperkalemiaBP control. ACEI can cause hyperkalemia• Rx of complicationsRx of complications• Admit if renal failureAdmit if renal failure

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Complications of AGNComplications of AGN• ARF (uremia/azotemia)ARF (uremia/azotemia)• Volume over-load: HTN: LVFVolume over-load: HTN: LVF• HTN: encephalopathy, convulsionHTN: encephalopathy, convulsion• HyperkalemiaHyperkalemia• AcidosisAcidosis• Microhematuria may persist for yearsMicrohematuria may persist for years• NSNS• CGN: 2%CGN: 2%

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APSGN: PrognosisAPSGN: Prognosis

• Excellent. Most recover completelyExcellent. Most recover completely• Mortality 2%Mortality 2%• CKD: 2% in children. CKD: 2% in children. 30% in adults30% in adults• ESRD 1-2%ESRD 1-2%• One attack confers lifelong immunityOne attack confers lifelong immunity

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SS of Glomerular Diseases SS of Glomerular Diseases

• May be silent for many yearsMay be silent for many years• Hematuria, proteinuria, azotemiaHematuria, proteinuria, azotemia• HTN, edema, hyperlipidemiaHTN, edema, hyperlipidemia

Some CRF can be slowed down, but scarred Some CRF can be slowed down, but scarred glomeruli cannot be repairedglomeruli cannot be repaired

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Glomerular Glomerular vsvs Non-G Hematuria? Non-G Hematuria?

• Chemical trauma to RBCs as they pass through nephrons Chemical trauma to RBCs as they pass through nephrons causes peculiar changes: they lose biconcavity & causes peculiar changes: they lose biconcavity &

have have blebs: blebs: “Mickey Mouse Cells”“Mickey Mouse Cells”

• RBC casts & proteinuria supports a GDRBC casts & proteinuria supports a GD

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Mickey mouse cells

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ProteinuriaProteinuriaNormal valuesNormal values

– Premature: Premature: 140 mg/m 140 mg/m22/d/d– FTFT 70 mg/m 70 mg/m22/d/d– Children <10yr Children <10yr 150 mg/d 150 mg/d– Children 10-18 yrChildren 10-18 yr 300 mg/d 300 mg/d– Adults Adults 150 mg/d 150 mg/d

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A 3y old child has heavy proteinuria with anasarca. No A 3y old child has heavy proteinuria with anasarca. No familial KD. No drugs. Wt 17 kg, BP 90/50; 4+ edemafamilial KD. No drugs. Wt 17 kg, BP 90/50; 4+ edema

Urine: 0-4 RBC/hpf. Numerous hyaline casts. Some lipid Urine: 0-4 RBC/hpf. Numerous hyaline casts. Some lipid inclusions appearing Maltese cross under polarized lightinclusions appearing Maltese cross under polarized light

What is the Dx?What is the Dx?

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Ans.: Nephrotic SyndromeAns.: Nephrotic Syndrome

• Massive proteinuria >3.5g/d (>40mg/mMassive proteinuria >3.5g/d (>40mg/m2 2 /hr)/hr)• Hypoalbuminemia: <30g/dlHypoalbuminemia: <30g/dl• AnasarcaAnasarca• HyperlipidemiaHyperlipidemia• LipiduriaLipiduriaAge: 1½ - 5yAge: 1½ - 5yBoys moreBoys more

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PeculiaritiesPeculiarities of Childhood NS of Childhood NS• Most cases: no inflammation/RFMost cases: no inflammation/RF• Most respond to steroidMost respond to steroid• Well for 3y: no more relapseWell for 3y: no more relapse• No relapse after 15yoaNo relapse after 15yoa• Auto-remission 5%Auto-remission 5%

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Spot urineSpot urine

Urinary albumin:creatinine Urinary albumin:creatinine >200>200Significant proteinuria: Significant proteinuria: >4mg/m>4mg/m22/h/hHeavy proteinuria: Heavy proteinuria: >40mg ,,>40mg ,,Remission:Remission: <4mg/m2/h<4mg/m2/h

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ClassificationClassification

CongenitalCongenitalAcquired:Acquired:

Primary: Primary: MCNS/MCD (MCNS/MCD (85% of NS in children)85% of NS in children)Secondary:Secondary:

Infection: HBV, HCV, malariaInfection: HBV, HCV, malariaSLE, HSP, SCD, PAN, HTN, DM SLE, HSP, SCD, PAN, HTN, DM

amyloidosis, malignancyamyloidosis, malignancy gold, penicillamine, Hg, Heavy metalgold, penicillamine, Hg, Heavy metal

NS of childhoodNS of childhood

MCD: 85%FSGS: 10%Others: 5%membranoproliferativeGN, mesangiocapillary GN, diffuse proliferative GN, congenital

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EpidemiologyEpidemiology• Incidence: 2-7/10,000/yIncidence: 2-7/10,000/y• x15 common in childrenx15 common in children• Non-immuneNon-immune factors in MCD & FSGS factors in MCD & FSGS• Immune factors in MPGN, PSGN & SLEImmune factors in MPGN, PSGN & SLE• Age of onset varies with type of diseaseAge of onset varies with type of disease

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Filtration barrier. Filtration barrier. A. A. The endothelium with fenestraThe endothelium with fenestraB. B. GBM: 1. lamina interna 2. L. densa 3. L. externaGBM: 1. lamina interna 2. L. densa 3. L. externaC. C. Podocytes: 1. enzymatic & structural protein 2. filtration slit 3. Podocytes: 1. enzymatic & structural protein 2. filtration slit 3. diaphragmdiaphragm 6363

• Steroid sensitiveSteroid sensitive (90%)(90%)

• Steroid resistant:Steroid resistant: no response in 4w (10%)no response in 4w (10%)

• SteroidSteroid dependent:dependent: relapse on 2 consecutive relapse on 2 consecutive occasions as steroid is being tapered or within 2w of occasions as steroid is being tapered or within 2w of being discontinuedbeing discontinued

• Remission: Remission: nil protein in morning urine x3dnil protein in morning urine x3d

• Relapse: Relapse: U. Protein: >40/m2/h or Albustix ≥++ x 3d U. Protein: >40/m2/h or Albustix ≥++ x 3d morning urine. morning urine. Frequent RFrequent R: ≥2 in 6mo of Dx.: ≥2 in 6mo of Dx. or or ≥≥4/y.4/y. Infrequent RInfrequent R: after 3 mo of remission: after 3 mo of remission

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MCDMCD

• Commonest in children• Light ME: Normal• EM: fusion of foot processes of visceral epith cells• IF: no immune complex deposit • Cause/mechanism unknown• Drammatic response to steroid• Excellent prognosis

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Focal Segmental Glomerulosclerosis Focal Segmental Glomerulosclerosis (FSGS) & (FSGS) & Membranoproliferative GN Membranoproliferative GN (MPGN)(MPGN)

• In 15% of childhood NS, a kidney biopsy shows In 15% of childhood NS, a kidney biopsy shows scarring or deposits in glomeruliscarring or deposits in glomeruli

• Steroid is less effective in these; need cytotoxicsSteroid is less effective in these; need cytotoxics• ACEI can decrease HTN & proteinuria & protect ACEI can decrease HTN & proteinuria & protect

kidneyskidneys

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C/FC/F

• M: F =2:1M: F =2:1• Gross edema, scanty Gross edema, scanty

urine, SoBurine, SoB• There may be an There may be an

antecedal URTI (specially in relapse)antecedal URTI (specially in relapse)• Others: Others: depressiondepression, lethargy, anorexia, skin striae, , lethargy, anorexia, skin striae,

diarrhea, AP, orthostatic hypotensiondiarrhea, AP, orthostatic hypotensionBedside urine: heavy proteinuriaBedside urine: heavy proteinuria

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InvestigationsInvestigations

• Urine RE, CSUrine RE, CS• UTP/spot urine ACR: >200UTP/spot urine ACR: >200• CBC, electrolytes, BUN, S. Cr., STP, AG ratio, CBC, electrolytes, BUN, S. Cr., STP, AG ratio,

cholesterol (specifically LDL)cholesterol (specifically LDL)• ANA; Anti-dsDNA, C3, HBsAg, HCVANA; Anti-dsDNA, C3, HBsAg, HCV• Renal USGRenal USG• CXR, MT, worms, before steroid RxCXR, MT, worms, before steroid Rx

DD: DD: CHF, cirrhosis, protein losing statesCHF, cirrhosis, protein losing states 7070

Renal BiopsyRenal Biopsy

RarelyRarely done in Paediatric cases. done in Paediatric cases. Consider in:Consider in:• Cong. NSCong. NS• >8y at onset>8y at onset• Steroid resistanceSteroid resistance• Frequent relapsesFrequent relapses• Significant nephritic featuresSignificant nephritic features

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ComplicationsComplications• Infection: Infection: loss of Ig, complement: UTI, SBP (commonest) loss of Ig, complement: UTI, SBP (commonest)

& pneumonia & pneumonia (pneumococcus)(pneumococcus)

• Thrombosis: Thrombosis: loss of antithrombin iii, antiplasmin & loss of antithrombin iii, antiplasmin & proteins S & C in urine, more coagulants by liver, proteins S & C in urine, more coagulants by liver, raised raised hct., relative immobility, steroidhct., relative immobility, steroid

• Hypovolemia:Hypovolemia: postural hypotensionpostural hypotension• From Drug toxicity:From Drug toxicity: steroid, nephrotoxcity from steroid, nephrotoxcity from

cyclosporin A or tacrolimuscyclosporin A or tacrolimus

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Management: GeneralManagement: General

• Check Check BP, wt, abdo. girth, I.O. chart, proteinuriaBP, wt, abdo. girth, I.O. chart, proteinuria• Bed rest in gross edemaBed rest in gross edema• Diet: lean protein Diet: lean protein (no role of excess protein), (no role of excess protein), low fat; low fat;

low-saltlow-salt• Salt & fluid restriction. Usually Salt & fluid restriction. Usually no diureticno diuretic• Hypovolemia & hypoalbuminemia: FFP 20ml/kg or salt Hypovolemia & hypoalbuminemia: FFP 20ml/kg or salt

poor albumin 20%poor albumin 20%• Anticoagulants can help decrease clottingAnticoagulants can help decrease clotting• Statins can help lower cholesterolStatins can help lower cholesterol

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Management: SpecificManagement: Specific

Objective: Objective: Rx underlying causeRx underlying cause• MCD: up to 8y age: no renal biopsyMCD: up to 8y age: no renal biopsy• Prednisolone 60mg/m2/d (not >80mg/d) Prednisolone 60mg/m2/d (not >80mg/d) x 6wx 6w, then , then

40mg/m2/d EAD for 6w 40mg/m2/d EAD for 6w then STOPthen STOP• Exclude TB, HBV, HCV or other infectionExclude TB, HBV, HCV or other infections s

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RelapseRelapse

• First 2: First 2: “treat same way”“treat same way”• Frequent R: Frequent R: keep steroid 0.5mg/kg EAD for 3-6 mo. If keep steroid 0.5mg/kg EAD for 3-6 mo. If

relapse: Levamisole EAD for 4-12 morelapse: Levamisole EAD for 4-12 mo• If still R: If still R: Cyclophosphamide x 8w plus Low Dose Cyclophosphamide x 8w plus Low Dose

PrednisolonePrednisolone• Still rStill relapse: elapse: Cyclosporin A for 1y plus LD Pred.Cyclosporin A for 1y plus LD Pred.

Other drugs: Tacrolimus, MycophenolateOther drugs: Tacrolimus, Mycophenolate

7575

SRNSSRNS

• Refer to specialized unitRefer to specialized unit• Full remission not achievedFull remission not achieved• Aim: lower proteinuria to non-nephrotic rangeAim: lower proteinuria to non-nephrotic range• Risk of HTN & renal failureRisk of HTN & renal failure• In FSGS: 20-40% risk of relapse post transplantIn FSGS: 20-40% risk of relapse post transplant

7676

SSNSSSNS• Toddler, pre-school• No HTN• Mild, intermittent

hematuria• Normal renal function• Excellent prognosis,

even if frequently relapsing

• No biopsy

SRNSSRNS• <1 year, > 8y• HTN common• Persistent haematuria• Often abnormal RF• Long term HTN & RF

• Biopsy needed: usual histology FSGS

7777

Congenital NSCongenital NS• First 3 mo of life. Large placenta: ~ 40% of BWFirst 3 mo of life. Large placenta: ~ 40% of BW• Drug resistant. High morbidity: PEM & sepsisDrug resistant. High morbidity: PEM & sepsis• Types: Types: Finnish type: Finnish type: most severe, AR. most severe, AR. Diffuse mesangial Diffuse mesangial

sclerosis: sclerosis: less severe, AR. less severe, AR. Denys-Drash syn.: Denys-Drash syn.: pseudohermaphroditism & Wilms T. pseudohermaphroditism & Wilms T. FSGS. FSGS. Secondary CNS: Secondary CNS: cong. syphiliscong. syphilis

• Rx.: Rx.: Intensive care: 20% albumin, nutrition, early unilateral Intensive care: 20% albumin, nutrition, early unilateral nephrectomy, RRTnephrectomy, RRT

7878

RxRx of Hypertension in NSof Hypertension in NS

• ACEI reduce BP & proteinuriaACEI reduce BP & proteinuria• Nifedipine Nifedipine 0.25mg/kg/dose s.l.; max 8 doses/d (not 0.25mg/kg/dose s.l.; max 8 doses/d (not

>2mg/kg/d or >2mg/kg/d or • Hydralazine Hydralazine 0.5-2mg/kg/d)0.5-2mg/kg/d)• Others: Others: Atenolol, MethyldopaAtenolol, Methyldopa• DiureticDiuretic is is ccontroversial. Use with caution. May be ontroversial. Use with caution. May be

dangerous in dangerous in hypovolemiahypovolemia

7979

Immunization in NSImmunization in NS

Immunocompromized:Immunocompromized: steroid 2mg/kg/d or 20mg/kg/d x steroid 2mg/kg/d or 20mg/kg/d x 14d14d

• No live vax.No live vax.• Killed vax./toxoids are safeKilled vax./toxoids are safe• Live vax. after 4w of stopping steroidLive vax. after 4w of stopping steroid• VZIG in case of exposureVZIG in case of exposure• Ig in case of measles expo. or cl. measlesIg in case of measles expo. or cl. measles

8080

NSNS APSGNAPSGNH/oH/o NilNil Preceding Strep. Preceding Strep.

Inf.Inf.Age Age 2-6y2-6y 5-15y5-15y

Edema Edema MassiveMassive Mild-moderateMild-moderate

Urine colorUrine color Clear Clear Coca-cola coloredCoca-cola coloredSediment Sediment Nil Nil Red coloredRed colored

Protein Protein 4+4+ 1-2+1-2+

Microscopy Microscopy Clear Clear Plenty RBCs, PCPlenty RBCs, PC

Casts Casts HyalineHyaline RBC castsRBC casts

Serum albuminSerum albumin Below 25g/dlBelow 25g/dl Normal Normal 8181

PrognosisPrognosis: :

in iin idiopathic NS of childhood is excellentdiopathic NS of childhood is excellentMortality Mortality 1-2%1-2%

8282

MCQMCQ

• In APSGN ABT is essential for the pt.In APSGN ABT is essential for the pt.• APSGN is an autoimmune DAPSGN is an autoimmune D• Strep. skin infx. can cause RhFStrep. skin infx. can cause RhF• Fruits are beneficial in APSGNFruits are beneficial in APSGN• In APSGN LVF can occur from myocarditisIn APSGN LVF can occur from myocarditis• Hyperkalemia is a recognized complication of Hyperkalemia is a recognized complication of

APSGNAPSGN

8383

MCQMCQ• MCD is common after 8yoaMCD is common after 8yoa• NS Dx always needs renal biopsyNS Dx always needs renal biopsy• Hematuria is common in childhood NSHematuria is common in childhood NS• Levamisole is effective in relapse NSLevamisole is effective in relapse NS• Usually there is renal failure in NSUsually there is renal failure in NS

8484

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Taiwan Blue Magpie (Urocissa caerulea)

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