Management of Nephrotic Syndrome

Management of Nephrotic Syndrome. Based on Paediatric Protocol for Malaysian Hospital.

1. Management of Nephrotic Syndrome Muhammad redzwan bin Abdullah (MBBS)

2. Definition Massive proteinuria defined by: a. Edema ( e.g Periorbital , vulval / scrotal, leg and ankle) b. Proteinuria >40mg/m 2 /hour (1g/m 2 /day); or early morning urine protein creatinine index of 200mg/ mmol c. Hypoalbuminemia of <25g/L d. Hypercholesterolemia

3. Etiology Primary or idiopathic nephrotic syndrome is the commonest Secondary causes include: Post-streptococcal gromerulonephritis Systemic Lupus Erythematosis Henoch-Schonlein purpura Infections ( e.g malaria) Allergens ( e.g Bee Sting)

4. 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

5. 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

6. Renal Biopsy? Not needed as 80% of cases have minimal change steroid responsive disease Indications include: Steroid resistant nephrotic syndrome (failed to achieve remission despite 4 weeks of adequate steroid therapy ); or Persistent hypertension; or Renal impairment; or Gross hematuria

7. 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

8. 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

9. Management of Complications Hypovolaemia Infuse 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.

10. 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 days Children with Steroid resistant nephrotic syndrome: Renal biopsy

11. 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.

12. 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

13. 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.

14. 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)

15. Summary of Steroid management

16. Steroid Resistant Nephrotic Syndrome Refer for renal biopsy Specific treatment will depend on the histopathology.

17. 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.

18. 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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