Management of

Nephrotic SyndromeMUHAMMAD REDZWAN BIN ABDULLAH (MBBS)

Definition

Massive proteinuria defined by:a. Edema (e.g Periorbital, vulval / scrotal, leg and ankle)b. Proteinuria>40mg/m2/hour (1g/m2/day); orearly morning urine protein creatinine index of 200mg/mmolc. Hypoalbuminemia of <25g/Ld. Hypercholesterolemia

Etiology

Primary or idiopathic nephrotic syndrome is the commonest Secondary causes include:1. Post-streptococcal gromerulonephritis2. Systemic Lupus Erythematosis3. Henoch-Schonlein purpura4. Infections (e.g malaria)5. Allergens (e.g Bee Sting)

Investigations

Intial Investigations include:• Full blood count• Renal profile (Urea, electrolyte, creatinine)• Serum cholesterol • Liver function tests (albumin) • Urine FEME (dipstick)• Quantitative urinary protein excretion

Other investigations tailored based on suspicious secondary causes.• Antinuclear factor / anti-dsDNA to exclude SLE.• Serum complement (C3, C4) levels to exclude SLE, post-infectious glomerulonephritis• ASOT titres to exclude Post-streptococcal glomerulonephritis• Malaria screening if history of travelled in endemic area

Renal Biopsy?

Not needed as 80% of cases have minimal change steroid responsive disease Indications include:

1. Steroid resistant nephrotic syndrome (failed to achieve remission despite 4 weeks of adequate steroid therapy ); or

2. Persistent hypertension; or3. Renal impairment; or4. Gross hematuria

General Management

Normal protein diet is recommended No added salt when child has edema Penicillin is recommended at diagnosis and during relapses Check for signs and symptoms of hypovolemia or hypervolemia

*Fluid restriction is not recommended unless has gross edema Diuretics (e.g Frusemide) is not necessary. If used, must used with caution Human albumin (20-25%, 0.5-1.0mg/kg) can be used with 1-2mg/kg

frusemide to produce diuretic

General Advice

Counsel patient and parents regarding high probability (85-95%) of relapse.

Home urine albumin monitoring (protein > 2+) Edema is a sign of relapse regardless urine FEME result Children on systemic corticosteroids or other immunosuppressive

agents should be treated like any immunocompromised child who has come into contact with chicken pox / measles

Immunisation: Pneumococcal vaccine should be administered to all children with nephrotic syndrome, during remission if possible

Management of Complications

HypovolaemiaInfuse Human Albumin at 0.5 to 1.0 g/kg/dose fast, or any volume expanders like human plasm. Do not give Frusemide.

Primary Peritonitis Parenteral penicillin and a third generation cephalosporin. Duration

of treatment: for 28 days or until remission. Thrombosis

Adequate treatment with anticoagulation is usually needed. Please consult a Paediatric Nephrologist.

Corticosteroid Treatment

Oral Prednisolone should be started at:• • 60 mg/ m²/day ( maximum 80 mg / day ) for 4 weeks followed by • • 40 mg/m²/every alternate morning (EOD) (maximum 60 mg) for 4 weeks• • Then reduce Prednisolone dose by 25% monthly over next 4 weeks• • Total duration of treatment: 3 months

80% of children will achieve remission (defined as urine FEME trace or nil for 3 consecutive days) within 28 daysChildren with Steroid resistant nephrotic syndrome: Renal biopsy

Relapse

Urine albumin excretion > 40 mg/m²/hour or urine FEME of ≥ 2+ for 3 consecutive days

These children do not need admission unless: grossly oedematous, or have any of the complications of nephrotic syndrome

Induction of relapse is with oral Prednisolone as follows:• 60 mg/m²/day ( maximum 80 mg / day ) until remission followed by• 40 mg/m²/EOD (maximum 60 mg) for 4 weeks only

Breakthrough proteinuria may occur with intercurrent infection and usually does not require corticosteroid induction if the child has no oedema, remains well and the proteinuria remits with resolution of the infection. However, if proteinuria persists, treat as a relapse.

Frequent Relapse

≥ 2 relapses within 6 months of initial diagnosis or ≥ 4 relapses within any 12 month period.

Treatment with oral Prednisolone as follows:• 60 mg/m²/day ( maximum 80 mg / day ) until remission followed by• 40 mg/m²/EOD (maximum 60 mg) for 4 weeks then• Taper Prednisolone dose every 2 weeks and keep on as low an alternate

day dose as possible for 6 months

Steroid dependent Nephrotic Syndrome

Defined as ≥ 2 consecutive relapses occurring during steroid taper or within 14 days of the cessation of steroids

Treatment:• If the child is not steroid toxic, re-induce with steroids and maintain

on as low a dose of alternate day prednisolone as possible• If the child is steroid toxic (short stature, striae, cataracts, glaucoma,

severe cushingoid features) consider cyclophosphamide therapy.

Cyclophosphamide Therapy

Begin therapy when in remission after induction with corticosteroids. Treatment options include cyclosporine and levamisole. Side effects of Cyclophosphamide therapy include leucopenia, alopecia,

haemorrhagic cystitis and/or gonadal toxicity Dose: 2-3 mg/kg/day for 8-12 weeks (cumulative dose 168 mg/kg) Monitor full blood count (leucopenia) and urinalysis (hemorrhagic

cystitis) 2 weekly. If relapsed after course of corticosteroid: started again with

corticosteroid therapy (if the child does not steroid toxic)

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Steroid Resistant Nephrotic Syndrome Refer for renal biopsy

Specific treatment will depend on the histopathology.

General management of the Nephrotic state

Control of edema by use of diuretics (e.g. Frusemide, Spironolactone) and restriction of salt.

ACE inhibitor (e.g. Captopril), or Angiotensin II receptor blocker (ARBs) (e.g. Losartan, Irbesartan) to reduce proteinuria

Control of hypertension: ACE inhibitor/ARBs. Penicillin prophylaxis (from primary bacteria peritonitis) Monitor renal function Nutrition: normal dietary protein content, salt-restricted diet. Evaluate calcium and phosphate metabolism.

References

Hussain Imam Hj. Muhammad Ismail., Ng, H., et al. (2005). Paediatric protocols for Malaysian hospitals. Kuala Lumpur: Ministry of Health. pp 279-284

Lissauer, T. and Clayden, G. (2012). Illustrated textbook of paediatrics. Edinburgh: Mosby. Pp 336-338

Mohamad Sham Kasim., Lim YN., et al. Consensus statement: management of idiopathic nephrotic syndrome in childhood. Kuala Lumpur: Academy of Medicine Malaysia. <www.acadmed.org.my/view_file.cfm?fileid=217>

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