Definition and epidemiology
Nephrotic syndrome is a triad of heavy proteinuria, hypoalbuminaemia and oedema, with hyperlipidaemia as a frequent fourth feature. In children it is defined by proteinuria ≥40 mg/m²/h (or ≥1 g/m²/day, or a spot urine protein:creatinine ratio ≥200 mg/mmol / ≥2 mg/mg) plus serum albumin <25 g/L. It is the commonest chronic glomerular disease of childhood, with an incidence of roughly 1.2–16 per 100,000 children; incidence is several-fold higher in South Asian children. Peak onset is 2–6 years, with a male predominance in early childhood.
The overwhelming majority of cases are idiopathic (primary) nephrotic syndrome. The original ISKDC cohort showed that ~90% of children who respond to steroids have minimal change disease on biopsy; focal segmental glomerulosclerosis and mesangioproliferative lesions account for most of the remainder. Response to steroids — not histology — is the strongest prognostic marker, which is why most children are treated empirically without a biopsy.
Clinical features
Periorbital and dependent oedema is the presenting sign, often misattributed to allergy. Look for facial puffiness on waking, ankle/scrotal/labial oedema, ascites, and weight gain. Frothy urine and oliguria are common. Children are usually normotensive; significant hypertension, gross haematuria or impaired renal function point away from minimal change disease and toward a secondary or non-MCD cause.
Complications drive much of the morbidity: hypovolaemia (abdominal pain, cool peripheries, tachycardia), infection (spontaneous bacterial peritonitis and pneumococcal sepsis — the nephrotic child is functionally immunodeficient), and a prothrombotic state with risk of venous and arterial thrombosis.
Diagnosis
The diagnosis is biochemical: confirm nephrotic-range proteinuria and hypoalbuminaemia. Baseline workup includes urinalysis and microscopy, urine protein:creatinine ratio, serum albumin, creatinine and electrolytes, lipid profile, and complement (C3/C4). Low C3 should prompt consideration of post-infectious GN, membranoproliferative GN or lupus nephritis. Indications for renal biopsy include age <1 year or >12 years, steroid resistance, persistent hypertension or haematuria, low complement, or impaired GFR.
See the full criteria: Childhood Nephrotic Syndrome
Red flags
- Age <1 year (consider congenital/genetic causes) or onset >12 years
- Steroid resistance — no remission after 4–6 weeks of daily corticosteroids
- Macroscopic haematuria, sustained hypertension, or rising creatinine
- Low serum C3/C4
- Acute abdomen, fever or shock — peritonitis/sepsis or hypovolaemia until proven otherwise
- Calf swelling, headache or focal neurology — thromboembolism
Management overview
First-episode SSNS is treated with prednisolone 60 mg/m²/day (max 60 mg) for 4–6 weeks, then 40 mg/m² (max 40 mg) on alternate days, tapered over subsequent weeks — IPNA recommends a total duration of 8–12 weeks. About 80–90% of children achieve remission. Supportive care: salt restriction, judicious diuretics only in significant oedema (with caution in hypovolaemia), 20% albumin for symptomatic hypovolaemia or refractory oedema, and pneumococcal/varicella vaccination once feasible. Penicillin prophylaxis is considered during gross oedema/ascites in some protocols.
Relapses are common; frequently-relapsing, steroid-dependent and steroid-resistant disease are managed with steroid-sparing agents (levamisole, mycophenolate mofetil, calcineurin inhibitors, cyclophosphamide or rituximab) and warrant pediatric nephrology referral. Steroid-resistant disease requires biopsy and genetic evaluation. Long-term concerns include steroid toxicity (growth, bone, ophthalmic) and progression to CKD in the steroid-resistant group.
References
- ISKDC. Kidney Int. 1978;13:159–165.
- Trautmann A, et al. IPNA recommendations for steroid-sensitive nephrotic syndrome. Pediatr Nephrol. 2023;38:877–919.
- ISPN revised guidelines for steroid-sensitive nephrotic syndrome, 2021.
Decision support for qualified clinicians only — verify against current primary guidelines and your clinical judgement.