Nephrotic syndrome

Nephrotic syndrome characterized by four components both clinical & biochemical *Generalized Oedema *Massive Proteinuria: above 1g/m 2 /day *Hypoalbuminemia: serum albumin less than 2.5g/dl *Hypercholesterolemia (>250mg/dl) Types of nephrotic syndrome 1. Primary or idiopathic90% 2. secondary10% 3. Congenital

Etiology: Primary or Idiopathic-90% 1. Minimal change disease 85% 2. Focal segmental glomerulosclerosis 10% 3. Mesangial proliferative Glomerulonephritis 5% Secondary- 10%(Membranous Glomerulonephritis & Membrano proliferative Glomerulonephritis) Other causes include 1. Systemic diseases Henoch Schonelin Purpura SLE Diabetes mellitus 2. Infections Hepatitis B,& C Infective endocarditis Syphilis Malaria HIV

3. Drugs- penicillamine gold salts captopril NSAID’s 4. Neoplasm's- Hodgkin’s lymphoma Leukemia Wilms tumour

PATHOPHYSIOLOGY Permeability of glomerular capillary membrane Proteinurea Hepatic protein synthesis including lipoproteins. Hyperlipidemia Transudation of fluid from intravascular compartment to interstitial space. Plasma oncotic pressure. Intravascular volume ADH Renal perfusion pressure Water reabsorption in collecting ducts Activate renin angiotensin aldosterone system Tubular reabsorption of sodium & water  Edema. Hypoalbuminimia

Pathology: Minimal change nephrotic syndrome *Light microscopy – Normal *Immunoflorescent microscopy - Normal *Electron microscopy shows fusion of foot processes of the glomerular epithelial cells.

Clinical features: *Minimal change disease affects younger children: 2-8yrs * M:F 2:1 *Initially there is periorbital swelling & Oliguria *Within few days Oedema becomes generalized when the patient has ascites, pleural effusion, & scrotal swelling in boys. *With marked Oedema there may be dyspnoea. *Clinically hypertension & hematuria occur in 10% of children but are transitory. *There may be Flank pain, diarrhoea or Anorexia.

Investigations: 1. Urinalysis- Proteinuria 3+ or hr Protein excretion > 1g/m2/24 hrs urinary Protein & Creatinine ratio >3 2.Serum- albumin 250mg/dl Normal C3 Normal renal function 3.Others- CBC usually normal, ESR raised Mantoux test to rule out TB Cxr to rule out Pulmonary pathology or pleural effusion.

Indications of Renal Biopsy Age at onset 8 years Age at onset 8 years Hypertension Hypertension Hematuria Hematuria Low plasma C3 Low plasma C3 Renal insufficiency Renal insufficiency Steroid resistance Steroid resistance

Management: *Admit *No addet table Salt in diet *Treat infections with appropriate antibiotics *Steroids Prednisolone 60mg/m2/24hr in 4 d/d for 28 days(4wks) followed by 40mg/m2/day as a single dose on alternate days for 2-3m. *Diuretics- Used cautiously only when the child is having respiratory distress due to ascitis *Salt free albumin

Daily Monitoring: *weight *Intake-output *Urinary Albumin *Abdominal girth *Blood Pressure

Important Definitions: Remission – Urine negative for protein for 3 consecutive days. Steroid resistant – If the child continues to have Proteinuria (2 plus or more) on steroid therapy after 8 wks. Relapse – Proteinuria with Oedema. Steroid dependent – Relapse while on alternate day therapy or within 28 days of stopping Steroid therapy. Frequent relapser – Four or more relapses in 12 months.

Indications for Treatment other than steroids * Steroid resistance *Steroid dependence *Frequent relapser Alternative treatments *Levamisole *Cyclophosphamide *Chlorambucil *Cyclosporine

Complications

Complications: Infection – commmon infections are: cellulitis, UTI, Peritonitis, Pneumonia common organisms are– Gram negative bacilli, Strep. Pneumoniae, Staphylococcus 1.  Risk of infections is due to  Urinary loss of: immunoglobulins Factor B of the alternate complement activation path Transferin 2.T cell abnormalities 3.Steroid therapy / Immunosuppressive drugs Thrombosis & embolism – Decreased intravascular fluid volume Increase in plasma clotting factors (fibrinogen, V & VIII) Decrease in plasma antithrombin III Complications of treatment- Steroids- Cushingoid effects, poor growth, git upsets, HTN, DM, Electrolyte imbalance, Cataract, Infections.

Prognosis

Prognosis: *Best prognostic indicator is steroid sensitivity. *Most children ultimately ‘lose’ the nephrotic syndrome towards adolescence.

Steroid responsiveness *Minimal change disease 92% *Mesangial proliferative Glomerulonephritis 55% *Focal segmental glomerulosclerosis 20% Response time *First two weeks80% *Three weeks85% *Four weeks 92%

* Poor prognostic factors are Hematuria Hypertension Hypocomplementemia Focal segmental sclerosis Steroid resistance

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