MBBS Lectures

5. WELCOME
ALL 55

6. 66
RENALRENAL
DISEASESDISEASES

7. At the end… you will learnAt the end… you will learn
• Kidney disease can beKidney disease can be aa silent killersilent killer
• Childhood Nephrotic Syndrome is mostly curableChildhood Nephrotic Syndrome is mostly curable
• APSGN mostly recoversAPSGN mostly recovers;; does nor recurdoes nor recur
• HematuriaHematuria in small children is usuallyin 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
77

8. 88

9. 99

10. Summary:
Renal Function
1010

11. Importance of kidneyImportance of kidney
• MainMain waste excreterwaste excreter
• MaintainsMaintains fluid-, electrolyte- & AB Balancefluid-, electrolyte- & AB Balance
• MakesMakes erythropoietinerythropoietin
• MakesMakes thrombopoietinthrombopoietin
• Excretes someExcretes some drugsdrugs
• Biotransforms/activatesBiotransforms/activates VDVD
ABB: acid base balance. VD: vitamin DABB: acid base balance. VD: vitamin D
1111

12. Peculiarities of Kidney DiseasesPeculiarities of Kidney Diseases
• May be asymptomaticMay be asymptomatic (silent killer)(silent killer)
• Symptoms can beSymptoms can be nonspecificnonspecific
• Few physical signsFew physical signs (lab tests are important)(lab tests are important)
• May present withMay present with jaundicejaundice in infantsin infants
• Important c/ofImportant c/of FTTFTT
• Long tract: moreLong tract: more obstruction, complicationsobstruction, complications
1212

13. 1313

14. 1414

15. 1515

16. 1616

17. Micros. H:Micros. H: in a well child: ~in a well child: ~ no testno test
if not x3 times over severalif not x3 times over several
mo.mo.
evaluate if HTN, CKD,evaluate if HTN, CKD,
casturia/proteinuria presentcasturia/proteinuria present
Gross H:Gross H: urine is red/tea/colaurine is red/tea/cola
colored. It is also mostlycolored. It is also mostly
benignbenign
Up to 5 RBC/HPF in urine isUp to 5 RBC/HPF in urine is
normal in childrennormal in children
1717

18. Causes:Causes: The most
frequent: UTI’s, stones
& tumor
GH is more in boys.GH is more in boys.
Assess by CF.Assess by CF.
VCUG is useful inVCUG is useful in
doubtful USG, UTI, ordoubtful USG, UTI, or
voiding problem.voiding problem.
Cystoscopy ifCystoscopy if
persistent or withpersistent or with
ambiguous imagingambiguous imaging
GH: gross hematuria. VCUG : voidingGH: gross hematuria. VCUG : voiding
cystourethrographycystourethrography
"one should
investigate hematuria
rather than treat it"

19. Henoch-Schonlein purpuraHenoch-Schonlein purpura
• Classic triad:Classic triad: purpurapurpura (100%),(100%), arthritis/arthralgiaarthritis/arthralgia (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 urine is normalFollow until urine is 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
1919

20. 2020
HS Purpuras:HS Purpuras: necrotizingnecrotizing
vasculitis in skinvasculitis in skin smallsmall
BV; usuallyBV; usually extensorextensor
surfaces ofsurfaces of limbs,limbs,
sometimessometimes buttocksbuttocks
A.P., V., gut bleedingA.P., V., gut bleeding::
vasculitis in GITvasculitis in GIT
Renal:Renal: commonest iscommonest is
hematuria. In adults:hematuria. In adults: moremore
severe & maysevere & may dev. to rapidlydev. to rapidly
progressingprogressing
crescentic GNcrescentic GN

21. Wilms T/Nephroblastoma:Wilms T/Nephroblastoma: commonest child kidney Ca.commonest child kidney Ca.
•Causes:Causes: unknown, ~genetic. Aniridia sometimes; certainunknown, ~genetic. Aniridia sometimes; certain
UT problems & hemihypertrophy. Most at 3y; rare at 8UT problems & hemihypertrophy. Most at 3y; rare at 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, Cr. CCr, CXR, CBC, CT abdo, IVU,USG, AXR, BUN, Cr. CCr, CXR, CBC, CT abdo, IVU,
urinalysis, tests to determine spreadurinalysis, tests to determine spread
•Rx:Rx: do not press belly.do not press belly. Staging. SurgeryStaging. Surgery asapasap. RadioRx &. RadioRx &
chemo-. often post surgery, depending on stagechemo-. often post surgery, depending on stage
•Prognosis:Prognosis: if no spread: 90% cureif no spread: 90% cure
•Complications:Complications: Spread to lungs, liver, bone, or brain.Spread to lungs, liver, bone, or brain.
HTN & kidney damage may occur as the result ofHTN & kidney damage may occur as the result of
the tumor or its Rxthe tumor or its Rx.. 2121

22. 2222

23. 2323

24. A Case History of hematuriaA Case History of hematuria
• A 12y-boy has hematuria. He has occasional dark urineA 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?
2424

25. 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
2525

26. 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
2626

27. TerminologiesTerminologies
Oliguria:Oliguria: hypouresishypouresis, urine output <1mL/kg/h in infants,, urine output <1mL/kg/h in infants,
<0.5 mL/kg/h in children, <400 mL/d in adults.<0.5 mL/kg/h in children, <400 mL/d in adults.
• It is a clinical hallmark of renal failure & a criterion forIt is a clinical hallmark of renal failure & a criterion for
Dx & staging AKIDx & staging AKI
• It is frequently acute; often the earliest s/of ARF &It is frequently acute; often the earliest s/of ARF &
poses a Dx & Rx challenge to the Dr.poses a Dx & Rx challenge to the Dr.
Anuria:Anuria: oror anuresis anuresis, is passage of <100ml/d., is passage of <100ml/d.
• It is often c/by ARF; may also occur due to severe obs.It is often c/by ARF; may also occur due to severe obs.
(kidney stones or T); may occur in ESRD(kidney stones or T); may occur in ESRD
• It is a more extreme reduction than oliguriaIt is a more extreme reduction than oliguria
2727

28. • Black water Fever:Black water Fever: malariamalaria hemolysishemolysis:: hemoglobinuriahemoglobinuria
• CKD/CRF:CKD/CRF: progressive RFprogressive RF over 3moover 3mo (Dm, HTN, GN)(Dm, HTN, GN)
• GN:GN: glomeruli & tubules inflamedglomeruli & tubules inflamed
• Mesangium:Mesangium: cells supporting glomeruli:cells supporting glomeruli: phagocyticphagocytic
• ARF:ARF: Ac. Renal FailureAc. Renal Failure
(hours-days)(hours-days)
GN: glomerulonephritisGN: glomerulonephritis
2828

29. 2929

30. • ESRD:ESRD: GFR <15ml. Rx:GFR <15ml. Rx: dialysis/transplantdialysis/transplant (RRT: renal(RRT: 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 breakto break
kidney stoneskidney stones
3030
ESRD: end stage renal disease. ATN: ac. Tubular necrosis

31. 3131
Renal medulla: composed mainly of tubulesRenal medulla: composed mainly of tubules
ATN:ATN: patchy/diffuse denudation of tubular cells with losspatchy/diffuse denudation of tubular cells with loss
of brush border (blue arrows); flattening of tubular cellsof brush border (blue arrows); flattening of tubular cells
due to tubular dilation (orange arrows); intratubulardue to tubular dilation (orange arrows); intratubular
casts (yellow arrows); & sloughing of cells formingcasts (yellow arrows); & sloughing of cells forming
granular casts (red arrow). Finally, intratubular obs. isgranular casts (red arrow). Finally, intratubular obs. is

32. ATN: muddy brown casts
3232

33. • HUS:HUS: destroysdestroys 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. Moreinherited. 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; destroyinherited, 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
3333

34. • Interstitial Nephritis:Interstitial Nephritis: Inflam. of supporting tissue ofInflam. 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
3434

35. Acute Kidney InjuryAcute Kidney Injury ((AKIAKI) () (ARFARF))
abrupt loss of RFabrupt loss of RF within 7d.within 7d. c/byc/by low RBFlow RBF (low BP),(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, FEm. acidosis, hyperkalemia, uremia, FE
imbalance, & effects on other systems, death. Moreimbalance, & effects on other systems, death. More
risk of CKDrisk of CKD
• CausesCauses areare numerousnumerous. Common:. Common:
– SevereSevere dehydration, sdehydration, shock, ac.hock, ac. hgehge
– BlockageBlockage of renal BV,of renal BV, obstructionobstruction in UTin UT
– Renal trauma, Ac.Renal trauma, Ac. GN, aGN, acc. PN. PN
• Rx.:Rx.: underlying cause & supportive like RRTunderlying cause & supportive like RRT
RF: 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 vessel3535

36. CKD (CRF):CKD (CRF): GFR <90ml/min/1.73mGFR <90ml/min/1.73m22
>3 mo>3 mo
5 stages5 stages
• GFR 90ml/min/1.73m2GFR 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
3636

37. Causes of CKDCauses of CKD
• Systemic:Systemic: DM, HTN,DM, HTN, SLE, HSP, IgAN, APSGN, HIV, HBV, HCVSLE, 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 & monocytemainly IgG, against neutrophil & monocyte
cytoplasm. Seen in some AID. Particularly associated with systemic vasculitis (ANCAcytoplasm. Seen in some AID. Particularly associated with systemic vasculitis (ANCA
vasculitides)vasculitides)
3737

38. Urea frost in CRF
3838

39. Goodpasture Syn.Goodpasture Syn. ((anti-GBM d.)anti-GBM d.)
• Aka Aka pulmo-renal syn. Anti-collagen Ab in lungs:pulmo-renal syn. Anti-collagen Ab in lungs: vasculitis: vasculitis:
hemorrhage. Kidneys:hemorrhage. Kidneys: GN (anti-GBM Abs)GN (anti-GBM Abs)
• Autoimmune d.;Autoimmune d.; 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 following URTI:IgA deposits following URTI:
silentsilent hematuria; may go for yrshematuria; may go for yrs
• Men more. All agesMen 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: 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

40. Paroxysmal Noc. Hb.uria (PNH)Paroxysmal Noc. Hb.uria (PNH)
Rare.Rare. AcquiredAcquired. Life-threatening d.. Life-threatening d. characterizedcharacterized
byby complement-induced IV hemolysiscomplement-induced IV hemolysis
• Some proteins cannot fix to RBCs to protect fromSome proteins cannot fix to RBCs to protect from
complements: hemolysis: Hemoglobinemia & Hb.uria;complements: hemolysis: Hemoglobinemia & Hb.uria;
at night/early morningat night/early morning
• Any age. May be f/byAny age. May be f/by aplastic a., AML, MDSaplastic a., AML, MDS
• SS:SS: RAP, backache, headache, SoB, clotting; dark urine; easyRAP, backache, headache, SoB, clotting; dark urine; easy
bruisingbruising
4040
MDS:MDS: myelodysplastic syn. SoB: short of breathingmyelodysplastic syn. SoB: short of breathing

41. 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
4141

42. 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 occurmost people survive >10 y after Dx. Death occur
from thrombosis or bleedingfrom thrombosis or bleeding
BMT: bone marrow transplantBMT: bone marrow transplant
4242

43. Ac NephriticAc Nephritic
(Glomerulonephritic)(Glomerulonephritic) Syn.Syn.
• Ac. inflam. of the glomeruli & nephronsAc. inflam. of the glomeruli & nephrons
Nephrotic SyndromeNephrotic Syndrome
• Affection of nephrons with leakage ofAffection of nephrons with leakage of
protein (usually noprotein (usually no inflam.) inflam.)
4343

44. GlomerulonephritisGlomerulonephritis
• Inflam. & proliferation of glomerular tissue with damage toInflam. & proliferation of glomerular tissue with damage to
basement membrane, mesangium/capillary endoth.basement membrane, mesangium/capillary endoth.
• Acute:Acute: hematuria, proteinuria & RBC casts. Often withhematuria, 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
4444

45. Ac Nephritis: causesAc Nephritis: causes
– Group A StreptococcusGroup 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.
4545

46. Ac. Post-Strep. Glom. N.Ac. Post-Strep. Glom. N.
• 15% of all GAS infx.;15% of all GAS infx.; mostly RTI (skin 10%)mostly RTI (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 streptococci
4646

47. PathophysiologyPathophysiology
 Exact mechanism is unclearExact mechanism is unclear
 Strep. itselfStrep. 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
4747

48. 4848

49. 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 least 2 features, & 40% have all95% have at least 2 features, & 40% have all
 Flank pain (stretching of renal capsule)Flank pain (stretching of renal capsule)
 Weakness, -/+ AP, anorexia, feverWeakness, -/+ AP, anorexia, fever
 Anasarca, SoBAnasarca, SoB,, coughcough
 HTN, HA, LVF, convulsionHTN, HA, LVF, convulsion
HTN: hypertension. HA: headache. HC: highHTN: hypertension. HA: headache. HC: high
Colored.Colored.
4949

50. Edema:Edema: 80-90%.80-90%. Presentation in 60%.Presentation in 60%.
• Low RBF due to glomerular hypercellularity: low excretionLow RBF due to glomerular hypercellularity: low excretion
of Na & urine: salt & water retentionof Na & urine: salt & water retention
Hypertension:Hypertension: 60-80%.60-80%. Severe in 50%.Severe in 50%. More in elderly.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 usuallyPlasma renin is usually lowlow; ACE inhibition could be an; 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%.HTN-encephalopathy 5-10%. Improve without anyImprove without any
neurological sequelaeneurological sequelae
5050

51. Oliguria:Oliguria: 10-50%10-50%
• In 15%, UOP is <200mL. Oliguria is indicative of the severeIn 15%, UOP is <200mL. Oliguria is indicative of the severe
crescentic form of the dcrescentic form of the d
• Diuresis occurs within 1-2wDiuresis occurs within 1-2w
Left ventricular dysfunctionLeft ventricular dysfunction
• With/-out HTN or pericardial effusion may be presentWith/-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
5151

52. Lab InvestigationsLab Investigations
• UrineUrine:: RBCs, RBC casts, WBC, +/++ proteinRBCs, RBC casts, WBC, +/++ protein
• FBC:FBC: dilutional anemia, leucocytosisdilutional anemia, leucocytosis
• Recent strep. infRecent strep. inf.: ASO,.: ASO, Anti-Dnase B,Anti-Dnase B, throat/wound CSthroat/wound CS
• Elevated ureaElevated urea ±± creatininecreatinine
• Low complement C3Low complement C3
Anti-Dnase B: Ab made against GAS. Raised levels indicate: Rh. F,
PSGN, Strep. throat or Strep. skin infection
5252

53. Renal BiopsyRenal Biopsy
• Declining Renal FunctionDeclining Renal Function
• Atypical presentationAtypical presentation
• F/history of renal DF/history of renal D
• Persistent HTN or gross hematuriaPersistent HTN or gross hematuria
• HypocomplementemiaHypocomplementemia
Hallmark in PSGNHallmark in PSGN is subepithelial ‘humps’is subepithelial ‘humps’
representing immune complex depositionrepresenting immune complex deposition
5353

54. DiagnosisDiagnosis
• CFCF
• Swab CS, positive ASO &/or anti-DNase BSwab CS, positive ASO &/or anti-DNase B
• C3 is typically low (normalizes 6-12w).C3 is typically low (normalizes 6-12w). But normalBut normal
C3 does not exclude itC3 does not exclude it
DDDD
• IgANIgAN
• HSPHSP
• SLESLE
• HUS, other inf.HUS, other inf. 5454

55. Rx Of APSGNRx Of APSGN
Mainly supportive.Mainly supportive. Bed restBed rest
• Fluid & salt restriction,Fluid & salt restriction, FEBFEB
• DiureticsDiuretics
• 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
5555

56. 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 immunity:One attack confers lifelong immunity: no recurrenceno recurrence
5656

57. 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 microhematuriaProlonged microhematuria (for years)(for years)
• Nephrotic SynNephrotic Syn
• CGN: 2%CGN: 2%
5757

58. SS of Glomerular DiseasesSS 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 scarredSome CRF can be slowed down, but scarred
glomeruli cannot be repairedglomeruli cannot be repaired
5858

59. GlomerularGlomerular vsvs Non-G Hematuria?Non-G Hematuria?
• Chemical trauma to RBCs occur while they pass throughChemical trauma to RBCs occur while they pass through
nephrons: peculiar changes: they lose biconcavity &nephrons: peculiar changes: they lose biconcavity &
have blebs:have blebs: “Mickey Mouse Cells”“Mickey Mouse Cells”
• RBC casts & proteinuria supports a GDRBC casts & proteinuria supports a GD
5959

60. Mickey mouse cells
6060

61. ProteinuriaProteinuria
Normal valuesNormal values
– Premature:Premature: ≤≤ 140 mg/m140 mg/m22
/d/d
– Full TermFull Term ≤≤ 70 mg/m70 mg/m22
/d/d
– Children <10yrChildren <10yr ≤≤ 150 mg/d150 mg/d
– Children 10-18 yrChildren 10-18 yr ≤≤ 300 mg/d300 mg/d
– AdultsAdults ≤≤ 150 mg/d150 mg/d
6161

62. A 3y old child has heavy proteinuria with anasarca. NoA 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 lipidUrine: 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?
6262

63. Nephrotic SynNephrotic Syn
• Massive proteinuria >3.5g/dMassive proteinuria >3.5g/d (>40mg/m(>40mg/m22
/hr)/hr)
• Hypoalbuminemia: <30g/dlHypoalbuminemia: <30g/dl
• AnasarcaAnasarca
• HyperlipidemiaHyperlipidemia
• LipiduriaLipiduria
Age: 1½ - 5yAge: 1½ - 5y
Boys moreBoys more
6363

64. 6464

65. PeculiaritiesPeculiarities of Childhood NSof Childhood NS
• Most cases: no inflammation/RF (MCD)Most cases: no inflammation/RF (MCD)
• 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%
6565

66. ClassificationClassification
Acquired:Acquired:
Primary:Primary: MCNS/MCD (MCNS/MCD (85% of NS in children)85% of NS in children)
Secondary:Secondary:
Infection: APSGN, HBV, HCV, malariaInfection: APSGN, HBV, HCV, malaria
SLE, HSP, SCD, PAN, HTN, DMSLE, HSP, SCD, PAN, HTN, DM
amyloidosis, malignancyamyloidosis, malignancy
gold, penicillamine, Hg, Heavy metalgold, penicillamine, Hg, Heavy metal
membranoproliferativemembranoproliferative GN, mesangiocapillary GNGN, mesangiocapillary GN
diffuse proliferative GNdiffuse proliferative GN
CongenitaCongenitall

67. NS of childhoodNS of childhood
MCD: 85%
FSGS: 10%
Others: 5%
6767
FSGS: focal segmental glomerulosclerosis

68. 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 & FSGSfactors in MCD & FSGS
• Immune factorsImmune factors in MPGN, APSGN & SLEin MPGN, APSGN & SLE
• Age of onset varies with type of diseaseAge of onset varies with type of disease
6868

69. Filtration membraneFiltration membrane
A. FenestratedA. Fenestrated endotheliumendothelium
B.B. GBM: 1. lamina interna 2. L. densa 3. L. externaGBM: 1. lamina interna 2. L. densa 3. L. externa
C.C. Podocytes: 1. enzymatic & structural protein 2. filtration slit 3. diaphragmPodocytes: 1. enzymatic & structural protein 2. filtration slit 3. diaphragm.
Disruption of slits or destruction of podocytes cause massive proteinuria
6969

70. Definitions:Definitions:
• 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 consecutiverelapse on 2 consecutive
occasions as steroid is being tapered or within 2w ofoccasions 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 inU. Protein: >40/m2/h or Albustix ≥++ x 3d in
morning urine sample, edemamorning urine sample, edema
Frequent R:Frequent R: ≥2 in 6mo.≥2 in 6mo. oror ≥≥4/y4/y
7070

71. MCDMCD
• Commonest in children
• Biopsy:
– Light Microscopy: normal
– Electron microscopy: fusion of foot processes
• Immunofluorescent: no immune complex deposit
• Cause/mechanism unknown
• Drammatic response to steroid
• Excellent prognosis
7171

72. Focal Segmental GlomerulosclerosisFocal Segmental Glomerulosclerosis (FSGS) &(FSGS) &
Membranoproliferative GNMembranoproliferative GN (MPGN)(MPGN)
• In 15% of childhood NS. Biopsy shows scarring orIn 15% of childhood NS. Biopsy shows scarring or
deposits in glomerulideposits in glomeruli
• Steroid is less effective; need cytotoxicsSteroid is less effective; need cytotoxics
• ACEI can decrease HTN & proteinuriaACEI can decrease HTN & proteinuria
7272

73. C/FC/F
• M: F =2:1M: F =2:1
• Gross edema, scantyGross edema, scanty
urine, SoBurine, SoB
• There may be anThere 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 hypotension
Bedside urine: heavy proteinuriaBedside urine: heavy proteinuria
7373

74. 7474

75. 7575

76. InvestigationsInvestigations
• Urine RE, CS. Urinary total proteinUrine RE, CS. Urinary total protein
• Urinary albumin:creatinine (ACR) >200
Significant proteinuria: >4 mg/m2
/h
Heavy 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 Rx (eCXR, MT, worms; before steroid Rx (exclude TB, HBV, HCVxclude TB, HBV, HCV
or other inf)or other inf)
DD:DD: CHF, cirrhosis, protein losing statesCHF, cirrhosis, protein losing states 7676

77. 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
7777

78. 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 fromsteroid, nephrotoxcity from
cyclosporin A or tacrolimuscyclosporin A or tacrolimus
7878

79. Management: GeneralManagement: General
• CheckCheck 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 proteinDiet: lean protein (no role of excess protein),(no role of excess protein), low fatlow fat
• Salt & fluid restrictionSalt & fluid restriction
• UsuallyUsually no diureticno diuretic
• Hypovolemia & hypoalbuminemia: FFP 20ml/kg or saltHypovolemia & 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
7979

80. RxRx
•Corticosteroids is the first step in Rx of MCD & biopsy is notCorticosteroids is the first step in Rx of MCD & biopsy is not
indicated.indicated. For steroid meet all these criteria:For steroid meet all these criteria:
•Age 1-8y. Normal kidney functionAge 1-8y. Normal kidney function
•No macroscopic hematuriaNo macroscopic hematuria
•No systemic features: F, rash, joint pain, wt lossNo systemic features: F, rash, joint pain, wt loss
•Normal complement levels. Negative ANANormal complement levels. Negative ANA
•Negative HIV, hepatitis B&CNegative HIV, hepatitis B&C
•No FH of kidney dNo FH of kidney d
8080

81. Kidney biopsyKidney biopsy is done if 1 or more of the following:is done if 1 or more of the following:
•Age <1y or >8yAge <1y or >8y
•Recurrent gross hematuriaRecurrent gross hematuria
•Relevant FH of kidney d., symptoms of systemic dRelevant FH of kidney d., symptoms of systemic d
•Positive viral screensPositive viral screens
•Additional criteria are lab. findings possibly indicative ofAdditional criteria are lab. findings possibly indicative of
2y NS or Idiopathic NS other than MCD:2y NS or Idiopathic NS other than MCD:
– Sustained raised creatinineSustained raised creatinine
– Low C3/C4 levels. Positive ANA. Positive anti–ds-DNA antibodyLow C3/C4 levels. Positive ANA. Positive anti–ds-DNA antibody
•Here, histology guides Rx, & steroids may/may not beHere, histology guides Rx, & steroids may/may not be
indicated depending on the underlying causeindicated depending on the underlying cause
8181

82. • In selected preadolescent >8y (≤12 y), empirical steroidIn selected preadolescent >8y (≤12 y), empirical steroid
Rx can be considered prior to kidney biopsy only under aRx can be considered prior to kidney biopsy only under a
pediatric nephrologist. Children >12y requirepediatric nephrologist. Children >12y require
biopsy due to the rising incidencebiopsy due to the rising incidence
of FSGS & other c/of nephrosisof FSGS & other c/of nephrosis
• Initial Rx:Initial Rx: Oral prednisone, 60mg/mOral prednisone, 60mg/m22
/d or 2mg/kg/d (max.,/d or 2mg/kg/d (max.,
60mg/d) 4–6w. Then, 40mg/m60mg/d) 4–6w. Then, 40mg/m22
or 1.5mg/kg (max.,or 1.5mg/kg (max., 40mg)40mg)
EAD 2–5mo with tapering, with a min. 12wEAD 2–5mo with tapering, with a min. 12w
8282

83. • Infrequent relapseInfrequent relapse (1 in 6mo or 1-3 in 12mo): dose(1 in 6mo or 1-3 in 12mo): dose (60(60
mg/mmg/m22
/d or 2mg/kg/d) until urinary protein is nil/d or 2mg/kg/d) until urinary protein is nil
x3d; then, 40mg/mx3d; then, 40mg/m22
or 1.5 mg/kg (max., 40mg)or 1.5 mg/kg (max., 40mg)
EAD for 4w,EAD for 4w, then stop or taperthen stop or taper
• Rx of frequent relapseRx of frequent relapse: continue infrequent relapse Rx: continue infrequent relapse Rx
for 3mo at lowest dose to maintain remission or usefor 3mo at lowest dose to maintain remission or use
steroid-sparing agents, alkylating agents,steroid-sparing agents, alkylating agents,
levamisole, calcineurin inhibitors,levamisole, calcineurin inhibitors,
mycophenolate mofetilmycophenolate mofetil
8383

84. 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 relapseIn FSGS: 20-40% risk of post transplant relapse
8484

85. 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
8585

86. 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 mesangialDiffuse 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, earlyIntensive care: 20% albumin, nutrition, early
unilateral nephrectomy, RRTunilateral nephrectomy, RRT
8686

87. RxRx of Hypertension in NSof Hypertension in NS
• ACEI reduce BP & proteinuriaACEI reduce BP & proteinuria
• NifedipineNifedipine 0.25mg/kg/dose s.l.; max 8 doses/d (not0.25mg/kg/dose s.l.; max 8 doses/d (not
>2mg/kg/d or>2mg/kg/d or
• HydralazineHydralazine 0.5-2mg/kg/d)0.5-2mg/kg/d)
• Others:Others: Atenolol, MethyldopaAtenolol, Methyldopa
• DiureticDiuretic isis ccontroversial. Use with caution. May beontroversial. Use with caution. May be
dangerous indangerous in hypovolemiahypovolemia
S.l.: sub lingualS.l.: sub lingual
8787

88. Immunization in NSImmunization in NS
Immunocompromized:Immunocompromized: steroid 2mg/kg/d orsteroid 2mg/kg/d or 20mg/d x20mg/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
8888

89. NSNS APSGNAPSGN
H/oH/o Preceding Strep.Preceding Strep.
Inf.Inf.
AgeAge 2-6y2-6y 5-15y5-15y
EdemaEdema MassiveMassive Mild-moderateMild-moderate
Urine colorUrine color ClearClear Coca-cola coloredCoca-cola colored
SedimentSediment NilNil Red coloredRed colored
ProteinProtein 4+4+ 1-2+1-2+
MicroscopyMicroscopy ClearClear Plenty RBCs, PCPlenty RBCs, PC
CastsCasts HyalineHyaline RBC castsRBC casts
Serum albuminSerum albumin Below 25g/dlBelow 25g/dl NormalNormal 8989

90. PrognosisPrognosis::
in iin idiopathic NS of childhood is excellentdiopathic NS of childhood is excellent
MortalityMortality 1-2%1-2%
9090

91. MCQMCQ
• In APSGN ABT is essentialIn 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 ofHyperkalemia is a recognized complication of
APSGNAPSGN
9191

92. 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
9292

95. Taiwan Blue Magpie (Urocissa caerulea)

96. ThankThank
YouYou
9696