CGPEDICON 2014 LECTURE SERIES

1. NEPHROTIC SYNDROME
Present Day Management
JWAHARLAL NEHRU HOSPITAL & RESEARCH CENTRE - BHILAI
Joint Director Medical & Health Services, HOD Pediatrics
Dr.G.Malini

2. • History & exam
Pay attention to - secondary etiologies
- prior therapies
- edema
- blood pressure
- anthropometry
- infections

3.  protein excretion > 40 mg/m2/hr
>1gm / m2/ day
 Normal range  <4 mg/ m2/hour
100mg/m2/day
First morning:spot urine alb/creatinine ratio (mg:mg)
– Normal = <0.2 (0.5 if <2yr)
– Nephrotic =2-3 : 1 (>2 )
- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1801

4. • Urine
• Complete Blood Count
• Renal parameters :
– Spot Urine Protein : Creatinine ratio
– Creatinine, urea, albumin, cholestrol
• Liver Function Test
• Urine culture & sensitivity
• PPD test & X- Ray chest
Additional Tests
• C3 and ASO
• ANA
• Hepatitis B surface antigen
• HIV testing

5. • Age below 12 months >10yrs
• Gross or persistent microscopic hematuria
• Low blood C3
• Sustained Hypertension
• Renal failure not attributable to hypovolemia
• Suspected secondary cause of nephrotic syndrome
• Family history
After initial treatment
• Diagnosis of steroid resistance
• Before starting calcineurin inhibitors
• SDNS and FRNS not responding to cytotoxic therapy.

6. : Remission & Reduce Risk Of Future Relapse
APN (German )regime 1993 – IPNG - IAP
Dose - 2mg/kg max of 60mg daily for 6 weeks
followed by 1.5mg/kg max 40mg for 6 weeks on alt days.
Agent – Prednisolone
longer remission and reduced relapse rate
*Cochrane Database system Rev2007;CD001533

7. • REMISSION by end of 2 weeks – usually.
• Minority respond after 4 weeks.
• Approximately 90-95% of children with MCNS respond to
corticosteroid therapy.
• In contrast, only 20% of children with FSGS experience clinical
remission with initial corticosteroid therapy
• >55% relapse multiple times
• No relapse or a single relapse almost 40%
IJPP 2012;14(2) IJPAug(2012)79(8):1044

8. Protocols in Pediatric Nephrology 1st ed, by Arvind Bagga et al.

9. • Proteinuria of 2+ is observed with a mild infection lasts
for a week or so.
• Observe for a few days & defer treatment for relapse.
• If a child is already on alternate day prednisolone the
dose of steroid may be doubled, but given on alternate
day for a week or two.
• Such brief episodes may not be considered as relapse.
Pediatric Nephrology 5th ed, by RNShrivastava & Arvind Bagga.

10. Frequent relapses Two or more relapses within 6 months of initial response,
or four or more relapses in any 12-month period
Steroid dependence Two consecutive relapses during corticosteroid therapy,
or within 14 days of ceasing therapy
• All children referred for revaluation.
• Determine Steroid threshold.
• Low dose alternate day pred 0.3mg to 0.7mg/kg - 9 – 18 months
• Change from alt day dose to daily dose during infection.

11. .
Prednisolone Threshold >0.5 - 0.7mg/kg/Alt Day Or steroid toxicity
Step 1
Step 2
Step 3
Step 4
Step 5
Revised guidelines for management of steroid-sensitive nephrotic syndrome.Indian J Nephrol 2008;18:31-9

12. • C3, ANA
• Anti- HIV antibodies
• Anti Parvovirus IgM
• Free T3, T4, TSH
• Renal histology by electron microscopy.
• Genetic testing: sequencing of NPHS2, NPHS1, WTI & other genes
PATHOLOGY:
• FSGS, MCNS, Mesangioproliferative
• Treatment of membranous & membranoproliferative are different.
Protocols in Pediatric Nephrology 1st ed, by Arvind Bagga et al.

13. Agent Dose Duration Efficacy
Calcineurin inhibitors
Cyclosporin 4-5mg/kg/ D 12-36 months 50-80%
Tacrolimus 0.1- 0.2mg/ kg/D 12-36 months 70-85%
Cyclophosphamide
Intravenous
Oral
500-750mg/m2 6 pulses 40-50%
2-2.5mg/kg/D 12weeks 20-25%
High dose steroids &
cyclophosphamide
Methylprednisolone
Or
Dexamethasone
20-30mg/kg/dose
4-5mg/kg/day
AD x6, weekly x8, monthly x 8
Fortnightly x 4, bimonthly x 4
30-50%
Prednisolone Tapering dose 18 months
Cyclophosphamide 2-2.5mg/kg/D 12weeks

14. • Prednisolone is a component of all regimens
• Initially 1mg/kg on alternate days for 1 to 3 months.Then
tapered .
• If sustained remission is present for 6 to 12 months then
may be discontinued .
• ACE inhibitors & angiotensin receptor blockers.

15.  Infections
 Thromboembolism (LMW heparin, heparin, then oral)
 Hypovolemia: (NS bolus, 5% alb 10-15 ml/k ,20% alb 0.5-1g/kg)
 Edema
 Loss of various binding proteins, (Thyroxine and vit D)
 Hyperlipidemia. (statins)
 Complicaions of treatment

16. Evidence of hypovolemia
No
Oral frusemide 1-3mg/kg
No response
Add spironolactone 2-4mg/kg
No response
Increase Frusemide 4-6mg/kg
No response
Add hydrochlorthiazide or metolazone
No response
Frusemide IV bolus or infusion
No response
20% albumin 1Gm/kg followed by IV frusemide
Head out water immersion & ultrafiltration

17. • Peritonitis-abd.pain, vomiting, diarrhoea.
• Pneumonia, cellulitis, fungal infections.
• Varicella-single dose of VZIG within 96 hrs of
exposure (125U min to 625U max) or IVIG
400mg/kg single dose & Acyclovir.
• MT positive with no TB-INH Px for 6 mths
evidence of active TB- AKT.

18. • Hypertension- ACEI, CCB, B blockers.
• Steroid toxicity
BP, growth, yearly eye exam, oral Ca and Vit D
supplements.
• Behavior/sleep changes
• Weight gain & obesity
• Acne & hirsuitism
• Adrenal suppression
• Acute pancreatitis
• Growth arrest & pubertal
delay
• Osteoporosis
• Increased susceptibility to
infection.
• Impaired glucose
metabolism
• Hypertension
• Cataract
• Risk of ulcer
• Hyperlipidemia

19. • High dose steroids >2wk - in past 1 year
• Stress= req IV fluids, during surgery, severe infections etc.
• Hydrocortisone 30-50 mg/m2 for duration of stress, (IV
hydrocortisone 2-4 mg/k/d) tapered by 50% of its dose
daily after that.
• Or followed by Oral prednisolone- 0.3-1 mg/kg/d
tapered rapidly.

20. • On Prednisolone >2mg/kg for more than 2weeks should not
receive live viral vaccine.
• Hib, HB, Pneumococcal-given but response blunted.
• (MMR, Varicella, OPV) avoided till 4 weeks after.
• Siblings - IPV

21. • Treat the initial episode adequately
• Prednisolone only for initial episode.
• Steroid responsiveness - Prognostic indicator.
• Parent education – essential.

23. • The proportion of MCNS that became non-relapsers rose from
44% at 1 year
69% at 5 years,
84% at 10 years.
Mortality <1%
• Steroid-resistant FSGS – 30 to 50% progress to ESRD by 15
years
ultimate treatment - renal transplantation
recurs in about 25% of renal allografts.
• Mesangioproliferative 50% progress to ESRD over 10 years