Renal ds

WELCOME

ALL 55

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RENALRENAL

DISEASESDISEASES

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 in small children is usually harmlessharmless

• 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- & AB Balancefluid-, electrolyte- & AB Balance• Makes Makes erythropoietinerythropoietin• MakesMakes thrombopoietin thrombopoietin• Excretes some Excretes some drugsdrugs• Biotransforms/activates Biotransforms/activates VDVD

ABB: acid base balance. VD: vitamin DABB: acid base balance. VD: vitamin D

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Peculiarities of Kidney DiseasesPeculiarities of Kidney Diseases

• May be asymptomatic May be asymptomatic (silent killer)(silent killer)

• Symptoms can be Symptoms can be nonspecific nonspecific

• Few physical signs Few physical signs (lab tests are important)(lab tests are important)

• May present with May present with jaundicejaundice in infantsin infants

• Important c/of Important c/of FTTFTT

• Long tract: more Long tract: more obstruction, complicationsobstruction, complications

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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 present

Gross 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: The most

frequent: UTI’s, stones

& tumor

GH is more in boys. GH is more in boys.

Assess by CF. VCUG is Assess by CF. VCUG is

useful in doubtful USG, useful in doubtful USG,

UTI, or voiding problem. UTI, or voiding problem.

Cystoscopy if Cystoscopy if

persistent or with persistent or with

ambiguous imagingambiguous imaging

GH: gross hematuria. VCUG : voiding GH: gross hematuria. VCUG : voiding

cystourethrographycystourethrography"one should investigate hematuria

rather than treat it"

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 kidneys70% affect kidneys• Histologically vasculitis, Histologically vasculitis, IgANIgAN• 90% fully recover. 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 skin vasculitis in skin small small BV; usually BV; usually extensor extensor surfaces of surfaces of limbs, limbs, sometimes sometimes buttocksbuttocks

A.P., V., gut bleedingA.P., 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 dev. to rapidly dev. to rapidly progressing progressing crescentic GNcrescentic GN

Wilms T/Nephroblastoma: Wilms T/Nephroblastoma: the commonest child kidney Ca.the commonest child kidney Ca.

•Causes: Causes: unknown, ~genetic. Aniridia sometimes; unknown, ~genetic. Aniridia sometimes; certain UT problems & hemihypertrophy. Most at 3y; certain UT problems & hemihypertrophy. Most at 3y; rare rare after 8after 8

•SS: SS: any of: AP, hematuria, constipation, F, malaise, ANV, any of: AP, hematuria, constipation, F, malaise, ANV, hernia, FH of Ca., abdo. mass, HTNhernia, FH of Ca., abdo. mass, HTN

•Lab.:Lab.: USG, AXR, BUN, CXR, CBC, creatinine, CCr, CT abdo, IVU, USG, AXR, BUN, CXR, CBC, creatinine, CCr, CT abdo, IVU, urinalysis, tests to determine spreadurinalysis, tests to determine spread

•Rx:Rx: do not press on belly. do not press on belly. Staging. Surgery Staging. Surgery asapasap. RadioRx & . RadioRx & chemo-. often after surgery, depending on the stagechemo-. often after surgery, depending on the stage

•Prognosis: Prognosis: if no spread: 90% cure if no spread: 90% cure

•Complications:Complications: Spread to lungs, liver, bone, or brain. HTN & Spread to lungs, liver, bone, or brain. HTN & kidney damage may occur as the result of the tumor or its Rx.kidney damage may occur as the result of the tumor or its Rx.

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A Case History of hematuriaA Case History of hematuria

• A 12y-boy has hematuria. He has occasional dark urine A 12y-boy has hematuria. He has occasional dark urine after heavy exerciseafter heavy exercise

• 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 Fever: Black water Fever: 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: GFR <15ml. Rx: GFR <15ml. Rx: dialysis/transplant dialysis/transplant (renal (renal

replacement therapy)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

2727ESRD: 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 abrupt loss of RF within 7d. within 7d. c/by low RBF (low BP), c/by low RBF (low BP),

renotoxins, inflam., or obs. of UTrenotoxins, inflam., or obs. of UT

• Dx.: Dx.: typically raised BUN & creatinine, or low UOPtypically raised BUN & creatinine, or low UOP

• Complications: Complications: m. acidosis, hyperkalemia, uremia, FE m. acidosis, hyperkalemia, uremia, FE imbalance, & effects on other systems, death. More imbalance, & effects on other systems, death. More risk of CKDrisk of CKD

• Causes Causes are are numerousnumerous. Common:. Common:– Severe Severe dehydration, sdehydration, shock, ac. hock, ac. hgehge

– BlockageBlockage of renal BV, of renal BV, obstructionobstruction in UT in UT

– Renal trauma, Ac. Renal trauma, Ac. GN, aGN, acc. PN. PN

• Rx.: Rx.: underlying cause & supportive like RRTunderlying cause & supportive like RRTRF: renal function. RBF: renal blood flow. RRT: renal replacement therapy. BV: blood vesselRF: renal function. RBF: renal blood flow. RRT: renal replacement therapy. BV: blood vessel

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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 E S R DE S R D

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Causes of CKDCauses of CKD

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

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

• 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) 3333

Urea frost in CRF

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Goodpasture Syn. Goodpasture Syn. ((anti-GBM d.)anti-GBM d.)

• AIDAID• Aka pulmo-renal syn. Anti-collagen Ab in lungs: Aka 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 ARBsAID: autoimmune d. GBM: glomerular basement membrane. RF: renal failure. TUP: total urinary AID: autoimmune d. GBM: glomerular basement membrane. RF: renal failure. TUP: total urinary

proteinprotein

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 to protect from Some proteins cannot fix to RBCs to protect from

complements: hemolysis: Hb.emia & Hb.uria; at complements: hemolysis: Hb.emia & Hb.uria; at night/early night/early

morningmorning

• Any age. May be f/by Any age. May be f/by 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. SoB: short of breathingmyelodysplastic syn. SoB: short of breathing

Investigations for PNHInvestigations for PNH

• Pancytopenia, Pancytopenia, Hb.emia & Hb.uriaHb.emia & Hb.uria• Coombs' testCoombs' test• Haptoglobin levelHaptoglobin 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 Affection of nephrons with leakage of

protein (usually noprotein (usually no 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 hematuria, proteinuria & RBC casts. Often with HTN, edema & impaired RFHTN, edema & impaired RF

• Chr.Chr.: : above with scarring of nephrons & progressive RFabove 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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Ac. Post-Strep. Glom. Nephrts.Ac. Post-Strep. Glom. Nephrts.• 15% of all GAS infx.; mostly RTI 15% of all GAS infx.; mostly RTI (skin 10%)(skin 10%)

• Lag period: Lag period: 2-3w2-3w

• 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 streptococci4242

PathophysiologyPathophysiology

Exact mechanism is unclearExact mechanism is unclear

Strep. itself Strep. itself does not attack the kidneydoes not attack the kidney Autoim. d: Autoim. d: both CMI & humoral. both CMI & humoral. Immune complex Immune complex

deposits in glomeruli, activates complement: inflam.deposits in glomeruli, activates complement: inflam.

Kidneys enlarge in ~50%Kidneys enlarge in ~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 A.P.S.G.N. of A.P.S.G.N. Preceding URTI, skin infx. by a few weeksPreceding URTI, skin infx. by a few weeks Most common: Most common: edema (puffy face), hematuria (100%, edema (puffy face), hematuria (100%,

gross 30%), & HTN, with/-out oliguriagross 30%), & HTN, with/-out oliguria. 95% have at . 95% have at least 2 features, & 40% have allleast 2 features, & 40% have all

Flank pain (stretching of renal capsule)Flank pain (stretching of renal capsule) Weakness, -/+ AP, anorexia, FWeakness, -/+ AP, anorexia, F Anasarca, SoB/Anasarca, SoB/exertional dysp.,exertional dysp.,

coughcough HTN, HA, LVF, convulsionHTN, HA, LVF, convulsion

HC: high coloredHC: high colored

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Edema Edema 80-90%80-90%

it is the presentation in 60%. Low RBF due to glomerular it is the presentation in 60%. Low RBF due to glomerular hypercellularity: low excretion of Na & conc. urine: salt & hypercellularity: low excretion of Na & conc. urine: salt & water retention (edema)water retention (edema)

Hypertension Hypertension 60-80%. Severe in 50%. More in elderly. 60-80%. Severe in 50%. More in elderly. Often transient. If persists: indicative of CKD or not APSGNOften transient. If persists: indicative of CKD or not APSGN

• Despite Na retention, atrial natriuretic peptide is raised. Despite Na retention, atrial natriuretic peptide is raised. Kidneys become unresponsive to itKidneys become unresponsive to it

• Plasma renin is usually low; ACE inhibition could be an Plasma renin is usually low; ACE inhibition could be an effective short-term Rx for this low-renin HTNeffective short-term Rx for this low-renin HTN

• HTN-encephalopathy 5-10%. Improvement without any HTN-encephalopathy 5-10%. Improvement without any neurological sequelaeneurological sequelae

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OliguriaOliguria• 10-50%10-50%• In 15%, UOP is <200mL. Oliguria is indicative of the severe In 15%, UOP is <200mL. Oliguria is indicative of the severe

crescentic form of the dcrescentic form of the d• Diuresis within 1-2wDiuresis within 1-2w

Left ventricular dysfunctionLeft ventricular dysfunction• With/-out HTN or pericardial effusion may be present With/-out HTN or pericardial effusion may be present

during the acute congestive & convalescent phasesduring the acute congestive & convalescent phases• Rarely, pulmonary hge occursRarely, pulmonary hge occurs

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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’ is subepithelial ‘humps’ representing immune complex depositionrepresenting immune 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). C3 is typically low (normalizes 6- 12w). But normal 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 APSGN

Mainly 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• Acidosis, hyperkalemiaAcidosis, hyperkalemia• Prolonged microhematuria (for years)Prolonged microhematuria (for years)• NSNS• CGN: 2%CGN: 2%

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APSGN: PrognosisAPSGN: Prognosis

• Excellent in childrenExcellent in children

• Most recover completelyMost 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 & have causes peculiar changes: they lose biconcavity & 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– Full TermFull Term ≤≤ 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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Nephrotic SynNephrotic Syn

• Massive proteinuria >3.5g/d (>40mg/mMassive proteinuria >3.5g/d (>40mg/m2 2 /hr)/hr)• Hypoalbuminemia: <30g/dlHypoalbuminemia: <30g/dl• AnasarcaAnasarca• HyperlipidemiaHyperlipidemia• LipiduriaLipiduria

Age: 1½ - 5yAge: 1½ - 5y

Boys 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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ClassificationClassification

Acquired: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, malaria

SLE, HSP, SCD, PAN, HTN, DM SLE, HSP, SCD, PAN, HTN, DM

amyloidosis, malignancyamyloidosis, malignancy

gold, penicillamine, Hg, Heavy metalgold, penicillamine, Hg, Heavy metal

CongenitalCongenital

NS of childhoodNS of childhood

MCD: 85%

FSGS: 10%

Others: 5%membranoproliferative

GN, mesangiocapillary

GN, diffuse proliferative GN

congenital

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FSGS: focal segmental glomerulosclerosis

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 Immune factors in MPGN, PSGN & SLEin MPGN, PSGN & SLE• Age of onset varies with type of diseaseAge of onset varies with type of disease

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Filtration membrane. Filtration membrane. 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. diaphragmPodocytes: 1. enzymatic & structural protein 2. filtration slit 3. diaphragm

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• 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, edema. morning urine, edema. Frequent RFrequent R: ≥2 in 6mo.: ≥2 in 6mo. 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• 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; need cytotoxicsSteroid is less effective; need cytotoxics

• ACEI can decrease HTN & proteinuriaACEI can decrease HTN & proteinuria

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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

6969

7070

7171

InvestigationsInvestigations• Urine RE, CS. UTP/Urine RE, CS. UTP/morning urine ACR: >200morning urine ACR: >200• Urinary albumin : creatinine (ACR) >200

Significant proteinuria: >4mg/m2/hHeavy proteinuria: >40mg ,,Remission: <4mg/ ,,

• CBC, electrolytes, BUN, S. Cr., S. albumin, AG ratio, CBC, electrolytes, BUN, S. Cr., S. albumin, 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 states7272

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

7373

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 hct., relative immobility, steroidraised hct., 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 fatlow fat

• Salt & fluid restrictionSalt & fluid restriction

• Usually 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

7575

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

7676

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: relapse: LevamisoleLevamisole EAD for 4-12 mo 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

7777

Steroid Resistant NSSteroid Resistant NS

• 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 post transplant relapse In FSGS: 20-40% risk of post transplant relapse

7878

SSNSSSNS• Toddler, pre-school

• No HTN

• Hematuria: Mild, intermittent

• Normal renal function

• Excellent prognosis, even if frequently relapsing

• No biopsy

SRNSSRNS• <1 year, > 8y

• HTN common

• Persistent

• Often abnormal RF

• Long term HTN & RF

• Biopsy needed: usual histology FSGS

7979

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 Intensive care: 20% albumin, nutrition, early unilateral nephrectomy, RRTunilateral nephrectomy, RRT

8080

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

S.l.: sub lingualS.l.: sub lingual

8181

Immunization in NSImmunization in NS

Immunocompromized:Immunocompromized: steroid 2mg/kg/d orsteroid 2mg/kg/d or 20mg/d x 20mg/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

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NSNS APSGNAPSGNH/oH/o 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 colored

Sediment 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 8383

PrognosisPrognosis: :

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

8484

MCQMCQ

• In APSGN ABT is essential In APSGN ABT is essential for the pt.for the pt.• APSGN is an autoimmune DAPSGN is an autoimmune D• Strep. skin infx. can cause Rh. FStrep. skin infx. can cause Rh. F• 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

8585

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• MCD is an AIDMCD is an AID

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