Nephrotic syndrome

Medical disese of kidneys seen commonly in children

1. Thanks...

2. Nephrotic Syndrome Prof. Imran Iqbal Department of Paediatrics Children’s Hospital & Institute of Child Health, Multan, Pakistan

3. Nephrotic Syndrome

4. Nephrotic Syndrome ? Usual Presenting feature is Oedema D/D of Oedema Nephrotic Syndrome Acute Glomerulonephritis Congestive Heart Failure Kwashiorkor Chronic Liver Disease Protein Losing Enteropathy Angioedema

5. OPD Urine Examination Protien = 2 + OR 3 + Urine protein/ creatinine ratio > 2 Nephrotic Syndrome likely

6. Proteinuria Spot urine Trace = 15mg/dl + = 30mg/dl ++ = 100mg/dl +++ = 300mg/dl ++++ = 2000mg/dl Dipstick Boiling P/C ratio

7. Heavy proteinuria ( > 40mg/m 2 /hour or > 50mg/kg/day) Hypoalbuminaemia (< 2.5g/dl) Oedema Hyperlipidaemia (> 220mg/dl) Nephrotic Syndrome

8. Typical Clinical Features Age 2-6 years Boys 70 % Facial Puffiness / marked edema Mild Diarrhea Oliguria Blood Pressure normal or low Anorexia

9. Other PRESENTATIONS of NS GENERALIZED BODY SWELLING- EDEMA, OLIGURIA Abdominal pain Acute kidney injury Infections Shock Thrombo -embolism Hypertension Routine urinalysis

10. EXAMINATION Clinical Assessment of Circulating Volume Toe Temp. Capillary Refill time B.P Pulse Rate, Volume Extent of Edema Infections Systemic Examination Weight, Height, Ideal weight for Height, Surface area

11. COMPLICATIONS Gross edema Hypovolemia Infections – peritonitis, cellulitis , UTI Pneumonia Tuberculosis Arterial / venous thrombosis

12. Atypical Clinical Features Age < 1 year or > 10 years Hematuria Hypertension Azotemia

13. Nephrotic Syndrome in Children Congenital/Infantile NS Primary Secondary Finnish Type DMS Deny –Drash Syndrome MCNS FSGS MN Galloway-Mowat Syndrome Nail-Petella Syndrome Congenital Infections HIV Malaria SLE Childhood NS Secondary SLE HSP Hep B Others Primary (Idiopathic) MCD FSGS DMP MPGN MN

14. Nephrotic Syndrome in Children Primary Nephrotic Syndrome - 95% Minimal Change Disease - 80 %

15. CAUSES OF SECONDARY Nephrotic Syndrome SLE HSP Hepatitis B, C HIV Malaria Lymphoma Drugs (NSAIDS)

16. SLE

17. Secondary NS - Causes Lupus nephritis (LN) HSP nephritis (HSPN) Hepatitis C nephritis - MPGN Hepatitis B nephritis – MN Malaria HIV nephritis Lymphoma Drugs

18. Minimal Change Disease Genetic factors T – cell activation Cytokines – IL 4 & IL 13

19. MCD - pathology

20. Albuminuria

21. PATHOPHYSIOLOGY Under-fill Hypothesis Heavy Albuminuria Hypoalbuminaema Reduced Plasma Oncotic Pressure Continuing Salt & Water Intake OEDEMA Renal Salt & Water retention Hypovolaemia Shift of fluid from plasma to interstitium Reduced GFR Increased proximal tubular salt & water reabsorption Activation of the RAAS Release of ADH Inhibition of atrial natriuretic peptide

22. Labs for Nephrotic Syndrome INITIAL INVESTIGATIONS Urine Exam Serum albumin Urea , Creatinine Lipid profile Na, K, Ca, CBC PT, APTT Subsequent Investigations HBsAg HCV antibody ASO titre USG abdomen Tuberculin test X ray Chest C3 , C4 Anti ds DNA antibodies

23. Management of Nephrotic Syndrome Patient COUNSELING Disease Urine Examination Medicines Complications Immunisations

24. MONITORING Daily home monitoring of proteinuria (PU) by dipsticks or boiling method and keeping diary Follow up every 4 weeks- check weight, BP, PU, edema, side effects of steroids and other medicines Height – every 6 months

25. Immunisations Avoid live vaccines Give Pneumococcal vaccine Pneumococcal conjugate vaccine Pneumococcal polysaccharide vaccine

26. SUPPORTIVE TREATMENT Diet Hypovolemia Diuretics Mucosal protectives Antihypertensives Infections

27. Gross Edema

28. DIURETICS- WHEN TO USE ? Very cautious and judicious use when : Generalized anasarca Massive ascities or pleural effusion causing respiratory difficulty Massive scrotal swelling with imminent skin rupture Concomitant albumin infusions are required to mobilize edema Persistent hypertension

29. DIURETICS-RISKS Intavascular volume depletion Thromboembolism Acute kidney injury Severe electrolyte imbalance

30. Steroid Sensitive Nephrotic Syndrome: 90% Steroid Resistant Nephrotic Syndrome: 10% Primary/ Idiopathic NS

31. Steroid Induction of Remission therapy Prednisolone 60 mg / m2 for 4 wks ( usual remission time 7 – 10 days ) If no remission: Continue same dose for another 4 wks OR MethylPrednisolone IV 30 mg / m2 alternate day for 3 doses

32. Continuation Steroid therapy If remission achieved: Prednisolone 40 mg / m2 alternate day for 4 wks Reduce dose by 5 – 10 mg every 4 weeks Stop treatment by 3 – 6 mo

33. Relapses in Nephrotic Syndrome Relapses 40 – 70 %

34. Treatment of Relapse Prednisolone 60 mg / m2 till remission Reduce dose by 5 – 10 mg every 4 weeks

35. Terminology Remission = urine albumin free for 3 days Relapse = urine albumin 3+ for 3 days Frequent Relapser = > 2 relapses in 6 mo or > 3 relapses in 12 mo Steroid Dependant = relapse within 14 days of reducing steroid dose Steroid Resistant = No response to initial steroid therapy in 4 – 8 weeks

36. Types of NEPHROTIC SYNDROME Steroid Sensitive NS (SSNS) Non Relapsing NS (NRNS) Infrequently Relapsing NS (IRNS) Frequently Relapsing NS (FRNS) Steroid Dependant NS (SDNS) Steroid Resistant NS (SRNS) Atypical NS Secondary NS

37. Treatment of Frequent Relapses Prednisolone 10 – 15 mg / m2 in Alternate day doses continued for 1 – 2 years Cyclophosphamide 2mg /kg for 12 weeks Mycophenolate Mofetil 30 mg / kg / day

38. Adverse effects of steroid therapy Infections Cushingoid appearance Emotional problems Hypertension Acid peptic disease Osteoporosis Impaired glucose tolerence Growth retardation

39. Iatrogenic Cushing’s Syndrome

40. MANAGEMENT OF SSNS First Episode of NS Trial of Steroids Response Withdraw Steroids over 6 months Relapse Repeat short Steroid course Infrequent relapse Frequent relapses Intermittent short steroid courses or Steroid dependency No Relapse, discharge Alternate day Steroids Steroids well tolerated Contd. AD Steroids Steroids not well tolerated Consider Alternatives

41. Renal Biopsy Steroid Resistance Age < 1 year >10 years Prolonged mild proteinuria Macroscopic haematuria Marked persistent HTN Persistent renal insufficiency low C3 or C4 Cyclosporine therapy

42. Prognosis of SSNS Relapses decreased after few years In some relapsing patients , Relapses may continue upto 14 – 20 years Renal insufficiency is rare

43. Predictors of prolonged course Early onset of disease Severity of proteinuria Frequent Relapses

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