2. BASICS
• Significant amounts of albumin, globulin etc are reabsorbed in PCT
• ‘Normal’ protein excreted in urine is Tamm-Horsefall *
• PROTENIURIA
• Glomerular
• Tubular
• ↑ production of plasma proteins
3.
4. BASICS……….CONTD.
• Dipsticks primarily detect albumin(1+ to 4+)
• False +ve ur. pH>7, concentrated urine, blood, pyuria
• False –Ve ur. pH<4.5, dilute urine, non-albumin
proteinuria(BJ, γ-glob)
• Protein excretion
• Normal <4mg/m2
• Abnormal-4-40 (Tubular)
• Nephrotic range >40
5.
6. URINE PROTEIN : CREATININE RATIO (UPC RATIO)
• Has largely replaced 24 hours Urinary Protein estimation
• Ur. Protein Conc. (mg/dL)/Ur. Creatinine Conc.(mg/dL)
• Done on 1st morning sample*
• Normal values: <0.5 in 0-2 yrs, <0.2 in >2 yrs
• UPC >2 Nephrotic range
• Microalbuminuria#- to detect diabetic nephropathy/obesity
7. TRANSIENT V/S ORTHOSTATIC PROTEINURIA
Transient Protenuria(TP)
Fever
Exercise
Cold Exposure
Seizures
Dehydration
CHF
Stress
Orthostatic Proteinuria(OP)
Most common in school going kids
Can go up to 1000 mg/24 hrs
No hematuria/HTN/edema/oliguria/
hypoalbuminemia
Correct collection of 1st sample is critical
Absence of Pr’uria & UPC<0.2 in 1st
morning sample on 3 consecutive days OP
8. FIXED PROTEINURIA (FP)
Glomerular plus
PIGN-HCV HBV IE HIV
HSP
SLE
Alport
Serum Sickness
Tubular
Cystinosis
Fanconi
Wilson
Lowe’s
Galactosemia
ATN
Renal Dysplasis
PKD
Drugs(AG)
Glomerular Isolated
Idiopathic NS
FSG
MPGN
MN
Diab NP
Sec causes
FP Urine with Sp.Gr.>1.015 having Pr>1+ on dipstick OR UPC > 0.2
9. EVALUATION OF A CHILD WITH PROTEINURIA
Persistent Asymptomatic Proteinuria
mostly glomerular in origin
Such pts should be evaluated every
4-6 mo for
B.P/Creatinine/UPC/Hematuria
Tubular Proteinuria
Low grade-UPC 0.2-1.0
Initial Evaluation
UPC
S. Creatinine
Electrolytes
S. Albumin
C3/C4
ANA
Indications for Renal Biopsy
UPC>1.0 – Increasing
trend
Hematuria
HTN
↓ Renal Function
11. PATHOGENESIS• Basic path↑permeability of glomerular
capillary wall
• Crucial role of PODOCYTE-highly specialized
cell-it’s a visceral epith cell lining the GBM
• 2 Podocytes are connected by – Slit
Diaphragm
• Slit Diaphragm- regulates protein filtration-
not just a passive filter-contains Signaling
proteins
12.
13. PATHOGENETIC MECHANISMS
• Signaling proteins (Podocyte Proteins)-
• Nephrin
• Podocin
• CD2AP
• ∝-Actinin4
• Immune/Non Immune insults to Podocytes cause
• Foot process effacement
• ↓ no of functional podocyte
• Altered slit diaphragm permeability
Podocyte injury or
genetic mutations of
genes producing
signaling proteins cause
nephrotic proteinuria
15. CLINICAL CONSEQUENCES OF NS-I
• Edema- most common symptom
• Cause – not clear-
• Underfill Hypothesis
• Overfill Hypothesis
• AIM is to gradually ↓ edema by careful use of diuretics, sos IV
Albumin
• Hypocalcemia
• Not a true hypocalcemia-due to ↓Se Albumin
• Due to urinary loss of Vit D binding protein
16. CLINICAL CONSEQUENCES OF NS-II
• Infections- ↑ed susceptibility
• Due to urinary Loss of IgG, C3, C5, alt pathway Factors B & D,
impaired opsonization capacity-due to loss of Properdin factor B
• ↑ risk of infection with encap. Bact esp PC, and Gr-ve bactSBP
• So child with NS c/o pain abdomen + fever- be alert to possibility of
SBP besides Mesenteric ischemia sec. to hypovolemia
17. CLINICAL CONSEQUENCES OF NS-III
• Hypercoagulability
• Due to vascular stasis/hemoconcn/ ↑plt ct/ ↑coag. F
levels
• ↑ed platelet counts with ↑ed aggregation
• ↑production of Fibrinogen & Ur loss of Antithrombotic f’s
(antithrombin III & protein ‘S’ & ‘C’)
• DVT Cerebral vein thrombosis, Renal V thrombosis pulm
v thrombosis
• Altered endothelial function
18. CLINICAL CONSEQUENCES OF NS-IV
• Hyperlipidemia-
• ↑Cholesterol, TGs,
• ↑ in LDL & VLDLsevere disease
• HDL normal
• Low Oncotic pressure triggers hepatic lipoprotein synthesis
• ↑es risk of MI & risk of progression to ESRD
21. IDIOPATHIC NS-1
• 90% kids with NS are Idiopathic- MCD
• Rest are-
• Focal & Segmental Glomerulosclerosis
• Membranous Nephropathy
• Membranoproliferative GN
• Mesangial Proliferation
• In MCD/MP- ↑ed no of mesangial cells & effacement of foot processes- 50% respond to
steroids
• In FSG-scarring of Glomerular tuft with ↓glom cap lumen- 20% respond to steroids
22. IDIOPATHIC NS-2
• M>F, 2:1, 2-6 years median age, can be seen as early as 6 months
• If an adolescent presents with NSFSG
• ATYPICAL FEATURES
• Ass. Hematuria
• HTN (Nephritic pic)
• Age<1
• +ve family h/o NS
• Presents with ARF
• DD in a child with Edema++++ PLE, CHF, Hepatic Failure, PEM, AGN
Against
diagnosis of
MCD
23. • C3
• ANA
• dS DNA
• HBsAg
• HCV
• HIV
• Renal Biopsy
DIAGNOSIS OF IDIOPATHIC NEPHROTIC SYNDROME
UPC
BUN/Creatinine
S.Albumin
Lipid profile
Electrolytes
IN
ALL
KIDS
IN KIDS >10 YRS
TO R/O SEC. FORMS
24. TREATMENT OF MCD-NS
• Short Admission is necessary
• TB must be r/o with MT & IGT
• Indications for RENAL BIOPSY
• HTN
• Hematuria(gross)
• <1 yr or >12 yrs
• ↓C3
• ARF
STEROID THERAPY
Prednisolone@60mg/m2 OR 2mg/kg single
dose(AM) or 4-6 weeks
Followed by
40 mg/m2 or 1.5 mg/kg qod for 8-20 weeks
Fb tapering over 2-5 months
FOLLOW UP
Adv. UPC every 2-3 weeks to see control of
proteinuria
Anthropometry & BP check
Periodic S. Albumin & Cholesterol levels
25.
26. • RESPONSE-
• Remission within 1st
4 wks
RELAPSE-UPC>2.0 or DS>2+
for 3 consec days
REMISSION-
UPC<0.2/DS <1+
for 3 consec. days
FREQUENT RELAPSING
2 or > in 1st 6 mo OR
Or >4 in 12 mo
STEROID DEPENDENT
Relapse during steroid tapering or
within 1st 2 wks of stopping Rx
STEROID RESISTANCE
No remission in 4 wks of
steroid Rx
27. RX OF SEQUELAE
EDEMA
Na restriction(1.5 g/day)
Fluid restriction
Frusemide-very cautiously
25% Albumin fb Lasix
DYSLIPIDEMIA
Low Fat Diet(<30% of
Cal.Req.)
HMG-CoA-??
INFECTIONS
Teach Parents to recognize
signs of infection
Life threatening SBP
Rx with Antibioticss which can
cover both PC & Gr-ve bacteria
THROMBO-
EMBOLISM
Cautious Hydration
Use of LMWH/Warfarin
OBESITY
Dietary counselling
Use of Steroid sparing Rx
28.
29. RELAPSE & RESISTANCE
• RELAPSE
• UPC>2.0 or DS>3+ on 3 consecutive days
• Triggered by URTI/AGE
• Rx in same way as initial Rx except duration is short
• Frequent Relapsers (>2 in 6 mo or >4 in 12 mo)-rest are infrequent relapsers
• RESISTANCE
• Caused by FGS/MCNS/MPGN
• Candidates for Renal Bx
• 50% risk of ESRD within 5 yrs
31. IMMUNIZATION IN NS
• Full PCV (13 valent & 23 valent) to
prevent against life threatening
pneumococcal SBP
• Influenza Vaccination annually
• Hold Live vaccines (MMR, Varicella) till
steroids are tapered to <1 mg/kg/day(or2
mg/kg/day-alt. days)
LIVE VACCINES ARE
CONTRAINDICATED IN
KIDS RECEIVING
STEROID SPARING
AGENTS