7. At the end… you will learnAt the end… you will learn
• Kidney disease can beKidney disease can be aa 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 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
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
17. 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/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. VCUG isAssess by CF. VCUG is
useful in doubtful USG,useful in doubtful USG,
UTI, or voiding problem.UTI, or 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/j. painarthritis/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
1919
20. 2020
PurpurasPurpuras ((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: it isit is
more severe &more severe & maymay
dev. to rapidlydev. to rapidly
progressingprogressing crescentic GNcrescentic GN
21. 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; rarerare
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. SurgeryStaging. 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% cureif 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.
2121
23. 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?
2323
24. 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
2424
25. 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
2525
29. • 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
2929
30. • 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
3030
31. Acute Kidney InjuryAcute Kidney Injury ((AKIAKI) () (ARFARF))
abrupt loss of RFabrupt 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, 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 vessel3131
32. 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
3232
33. 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 & 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) 3333
35. 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 isIt 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: silentIgA deposits after URTI: silent
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 urinaryAID: autoimmune d. GBM: glomerular basement membrane. RF: renal failure. TUP: total urinary
36. Paroxysmal Noc. Hb.uria (PNH)Paroxysmal Noc. Hb.uria (PNH)
Rare.Rare. Acquired. Life-threatening d. characterizedAcquired. Life-threatening d. characterized
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: Hb.emia & Hb.uria; atcomplements: hemolysis: Hb.emia & Hb.uria; at night/earlynight/early
morningmorning
• Any age. May be f/byAny age. May be f/by aplastic a., AML, MDSaplastic a., AML, MDS
• SS:SS: RAP, backache, HA, SoB, clotting; dark urine; easyRAP, backache, HA, SoB, clotting; dark urine; easy
bruisingbruising
3636
MDS:MDS: myelodysplastic syn. SoB: short of breathingmyelodysplastic syn. SoB: short of breathing
37. 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
3737
38. 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
3838
39. 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.)
3939
40. GlomerulonephritisGlomerulonephritis
• Inflam. & proliferation of glomerular tissue with damage toInflam. & proliferation of glomerular tissue with damage to
BM, mesangium/capillary endotheliumBM, mesangium/capillary endothelium
• 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
4040
41. 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.
4141
42. Ac. Post-Strep. Glom. Nephrts.Ac. Post-Strep. Glom. Nephrts.
• 15% of all GAS infx.; mostly RTI15% 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 AgeAny 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
4242
43. 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 complexImmune 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
4343
45. 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
4545
46. EdemaEdema 80-90%80-90%
it is the presentation in 60%. Low RBF due to glomerularit 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)
HypertensionHypertension 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 anPlasma 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 anyHTN-encephalopathy 5-10%. Improvement without any
neurological sequelaeneurological sequelae
4646
47. OliguriaOliguria
• 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 within 1-2wDiuresis 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
4747
49. 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
4949
50. 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 normalBut normal
C3 does not exclude itC3 does not exclude it
DDDD
• IgANIgAN
• HSP, SLEHSP, SLE
• HUS, other inf.HUS, other inf.
5050
51. 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
5151
53. 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
5353
54. 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
5454
55. GlomerularGlomerular vsvs Non-G Hematuria?Non-G Hematuria?
• Chemical trauma to RBCs as they pass through nephronsChemical trauma to RBCs as they pass through nephrons
causes peculiar changes: they lose biconcavity & havecauses 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
5555
57. 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
5757
58. 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?
5858
61. PeculiaritiesPeculiarities of Childhood NSof 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%
6161
62. 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, DMSLE, HSP, SCD, PAN, HTN, DM
amyloidosis, malignancyamyloidosis, malignancy
gold, penicillamine, Hg, Heavy metalgold, penicillamine, Hg, Heavy metal
CongenitalCongenital
63. NS of childhoodNS of childhood
MCD: 85%
FSGS: 10%
Others: 5%
membranoproliferative
GN, mesangiocapillary
GN, diffuse proliferative GN
congenital
6363
FSGS: focal segmental glomerulosclerosis
64. 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, PSGN & SLEin MPGN, PSGN & SLE
• Age of onset varies with type of diseaseAge of onset varies with type of disease
6464
65. Filtration membrane.Filtration membrane. A.A. The endothelium with fenestraThe endothelium with fenestra
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
6565
66. • 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 3dU. Protein: >40/m2/h or Albustix ≥++ x 3d
morning urine, edema.morning urine, edema. Frequent RFrequent R: ≥2 in 6mo.: ≥2 in 6mo. oror ≥≥4/y.4/y.
Infrequent RInfrequent R: after 3 mo of remission: after 3 mo of remission
6666
67. 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
6767
68. Focal Segmental GlomerulosclerosisFocal Segmental Glomerulosclerosis (FSGS) &(FSGS) &
Membranoproliferative GNMembranoproliferative GN (MPGN)(MPGN)
• In 15% of childhood NS, a kidney biopsy showsIn 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
6868
69. 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
6969
72. 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
/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 RxCXR, MT, worms, before steroid Rx
DD:DD: CHF, cirrhosis, protein losing statesCHF, cirrhosis, protein losing states 7272
73. 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
74. 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
7474
75. 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
7575
76. 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 6w40mg/m2/d EAD for 6w then STOPthen STOP
• Exclude TB, HBV, HCV or other infectionExclude TB, HBV, HCV or other infectionss
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77. 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. Ifkeep steroid 0.5mg/kg EAD for 3-6 mo. If
relapse:relapse: LevamisoleLevamisole EAD for 4-12 moEAD for 4-12 mo
• If still R:If still R: Cyclophosphamide x 8w plus Low DoseCyclophosphamide 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
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78. 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
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79. 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
80. 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
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81. 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
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82. 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
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85. 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
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86. 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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পাবনা সুজানগরের গাজনার বিল I আকাশে পানিতে ছড়িয়ে আছে নীল্ আর নীল্ ।
Papilloma is a benign epithelial T growing outward in nipple-like & often finger-like fronds. It refers to the projection created by the T, not a tumor of a papilla (nipple)
HSP: a immune-related, small-BV vasculitis. IgA-C3 immune complex deposits in BV & elsewhere. Cause is unknown. Commonest in 3-8y (commonest vasculitis of childhood)
Incidence: 1/5000 children/y; occurs in adults too. Many have strong atopy, & usually follow URTI. It may be that deposition of IgA & C3 is related to an overzealous immune response to a preceding inf. IF: prominent deposition of IgA (sometimes IgG & C3) in the mesangial region; pattern looks so much like IgAN (best to think of HSP & IgAN as faces of the same d)
Rx is usually supportive. Steroids may reduce the chance of severe renal d. In some cases, it recurs, usually manifesting with bouts of hematuria
Proliferative extracapillary GN or crescentic GN is not a specific d, but a feature of severe glomerular damage. Extracapillary proliferation designates the cellular and/or fibrous proliferation that occupies the Bowman’s space. There is no universal agreement on the percentage of involved glomeruli to diagnose crescentic GN: usually &gt; or = 50%. Definition of crescent is the presence of at least 2 layers of cells that are filling totally or partially Bowman’s space
Mechanical hemolytic a. is due to mechanically induced damage to rbc. RBCs, while flexible, may in some circumstances succumb to physical shear & compression. This may result in hemoglobinuria. The damage is c/by repetitive mechanical motions like prolonged marching (march hb.uria), marathon running, & bongo drumming. Mechanical damage can also be due to chr. condition: microangiopathic hemolytic a or due to prosthetic heart valves.[1]
Glomerular mesangium is associated with the capillaries. It is continuous with the smooth muscles of the arterioles; outside the lumen, but surrounded by capillaries. It is in the middle (meso) between the capillaries
(angis). Both are contained by same BM. This term is often used interchangeably with mesangial cell, but in this context refers specifically to the intraglomerular mesangial cells. These cells are phagocytic & secrete BM (mesangial matrix). They are typically separated from the lumen of the capillaries by endothelial cells
Alport Syn? hematuria as the commonest & males affected more severely; can also affect cochlea & eye. Prevalence: 1/5,000. C/by mutations affecting type IV collagen, a major part of basement m. 80% X-linked. 20% is AR/AD
Kidneys: always affected. Hematuria is usually microscopic; sometimes for several days, associated with a cold or flu. This gross hematuria eventually stops when the child recovers & can be very frightening but is not harmful. As boys get older, they begin to show additional signs: proteinuria & HTN. These usually occur by the time the boys are teenagers. AS causes damage to the kidneys by formation of scar (glomeruli & tubules). Proteinuria damages the filtering system or glomeruli because of the abnormal collagen makeup (fibrosis: CKD). X-linked Alport develops CRF by the teenage years or early adulthood, but the onset of kidney failure can be delayed 40-50y of age. Carriers have no kidney failure. However, as women age, the risk of kidney failure increases. AD is usually well into middle age before CRF
Inner Ear: Hearing loss is never present at birth but becomes apparent by late childhood or early adolescence, generally before CRF. Some families have no deafness. Hearing aids are usually v effective. 80% of boys with X-linked AS develop hearing loss at some point in their lives, often by the time they are teenagers. In girls with X-linked AS hearing loss is less frequent & occurs later in life. AR typically have childhood hearing loss. Patients with AD develop hearing loss at a later age
Eyes: Anterior lenticonus is an abnormality in the shape of the lens of the eye (15-20% of X-linked & AR). People with anterior lenticonus may have a slow progressive deterioration of vision requiring patients to change the prescription of their glasses frequently. This condition may also lead to cataract formation. Some people have abnormal pigment of the retina called dot-and-fleck retinopathy, but this does not result in any abnormalities of vision. Recurrent corneal erosion can occur; & may need to take measures to protect their corneas from minor trauma such as wearing goggles when riding a bicycle
BUN measures amount of N in blood urea from protein metabolism. BUN test is done to see how kidneys work. HF, dehydration, or a diet high in protein can also make it higher. Liver d/damage can lower it. A low BUN level can occur normally in 2TM/3tm of preg
Goodpasture syn: a rare d that can quickly worsen. RF & lung d. Some forms involve just the lung or the kidney, but not both.
Causes: AID; mistakenly attacks & destroys collagen in alveoli & GBM. Sometimes is triggered by a viral resp inf or by breathing in hydrocarbon solvents. In such cases, the immune system may attack organs or tissues because it mistakes them for these viruses or foreign chemicals. The immune system&apos;s faulty response causes bleeding in the air sacs of the lungs & inflam in the kidney. Men are x8 likely. It commonly occurs in early adulthood.
Symptoms: may occur very slowly over months or even years, but they often develop v quickly over days to weeks. Anorexia, fatigue, & weakness are common. Lungs: Coughing up blood, Dry cough, SoB.
Kidney & other symptoms: Bloody urine, dysuria, NV, Pallor, edema
Exams & Tests
PE: HTN, & fluid overload. abnormal heart & lung sounds.
Urinalysis usually abnormal: blood & protein in urine. Abnormal rbc may be seen.
Tests: Anti-GBM, ABG, BUN, CXR, Creatinine, Lung biopsy, Kidney biopsy
Rx.: goal is to remove harmful Ab. Plasmapheresis removes whole blood from the body & replaces the plasma with fluid, protein, or donated plasma. Removing harmful Ab may reduce inflam in the kidneys & lungs.
Prednisone & other drugs suppress or quiet the immune system.
Controlling BP is the most important way to delay kidney damage. ACEI inhibitors & ARBs. Salt & fluids limit. A low to moderate protein may be recommended.
Closely watch kidney failure. Dialysis. Kidney transplant. A transplant is not done until the level of harmful antibodies drops.
Outlook: An early Dx is v imp. Much worse if the kidneys are severely damaged. Lung damage can range from mild to severe. Many need dialysis or transplant.
Complications: CKD, ESRD, Lung failure, Rapidly progressive GN, Severe lung bleeding
Prevention
Never sniff glue or siphon gasoline with your mouth, which expose the lungs to hydrocarbon & can cause the disease.
Alternative Names
Anti-glomerular basement membrane antibody disease; Rapidly progressive glomerulonephritis with pulmonary hemorrhage; Pulmonary renal syndrome; Glomerulonephritis - pulmonary hemorrhageAnti-glomerular basement membrane antibody disease; Rapidly progressive glomerulonephritis with pulmonary hemorrhage; Pulmonary renal syndrome; Glomerulonephritis - pulmonary hemorrhage
PNH (Marchiafava-Micheli syn.) Hb.uria & thrombosis. PNH is the only hemolytic a. which is mostly c/by an acquired intrinsic defect in CW (deficiency of glycophosphatidylinositol). It may be primary or in aplastic a. 26% have the telltale red urine in the morning. Allogeneic BMT is the only cure, but has significant MM. Eculizumab is effective, improving QoL, & reducing the risk of thrombosis
Myelodysplastic Syndromes (MDS) are a group of diverse BM d in which BM does not produce enough healthy cells. It is often referred to as a “BM failure d”. MDS is primarily a d of the elderly (most &gt;65), but can affect younger pts. as well. Stem cells, progenitor cells, or blasts — that normally mature; in MDS, they may not mature & may accumulate or may have a shortened life span, resulting in fewer than normal mature cells in blood. Low blood cell counts or cytopenias, are a hallmark of MDS: inf, anemia, bleeding. In addition to reduced numbers of cells, the mature blood cells circulating may not function properly because of dysplasia. The formal definition of dysplasia is the abnormal shape&appearance, or morphology, of a cell. Myelodysplasia refers to the abnormal shape&appearance of the mature blood cells. Failure of BM to produce mature healthy cells is a gradual process,&therefore MDS is not necessarily a terminal d. Some patients do succumb to the direct effects of the d. In addition, for roughly 30% of pts. Dx with MDS, this type of BM failure syndrome will progress to AML
Gene is called PIG-A.
BMT: BM transplantation
IF: Immunofluorescence
FEB: fluid & electrolyte balance
Podocytes in Bowman capsule that wrap capillaries with long foot processes. They have slit diaphragm or filtration slit. Podocytes can regulate GFR by contraction/closure of filtration slits. Disruption of slits or destruction of podocytes cause massive proteinuria
