Nephrotic syndrome tends to arrive without warning. A child with puffy eyes at breakfast looks unrecognisable by tea time. The face fills, the legs swell, the tummy distends, and the family ends up in A&E being told about kidneys and protein and steroids when an hour ago everything was fine.
Once the diagnosis lands, most of the work happens at home: a urine dipstick on the kitchen counter, a written plan from the consultant, and parents who've learned to read the early signs of a relapse and act on them. That literacy is what keeps relapses from becoming emergencies.
Healthbooq covers paediatric kidney conditions and how families learn to manage them between hospital visits.
What Is Going Wrong
The glomerulus is the kidney's filter — a tuft of capillaries with a three-layer barrier (endothelium, basement membrane, podocyte foot processes) that lets water and small molecules through but holds proteins back. In nephrotic syndrome, the podocyte layer becomes leaky and albumin slips through into the urine. Once albumin levels in the blood drop, the osmotic pressure that normally holds water inside vessels falls, and water moves out into the tissues. That is the swelling.
The liver tries to compensate by churning out more proteins — including lipoproteins — and the result is high blood cholesterol and triglycerides. The classic four findings of nephrotic syndrome (heavy protein in urine, low blood albumin, oedema, high lipids) all flow from one underlying problem: a podocyte that has stopped doing its job.
In children, the underlying biopsy diagnosis in over 90% of cases is minimal change disease. Under a light microscope the glomeruli look normal; only electron microscopy shows the foot processes are flattened. The reason it happens is still being worked out — the leading theory implicates dysregulated T-cells releasing a permeability factor that targets podocytes. The good news: minimal change disease is highly steroid-responsive.
Who Gets It
About 2 to 7 per 100,000 children per year. The peak age is 2 to 5 years. Boys outnumber girls roughly 2:1 in childhood; that ratio evens out after puberty. South Asian children have a notably higher incidence — closer to 9 to 16 per 100,000 — for reasons not fully explained.
What Parents Notice First
Periorbital oedema is almost always the opening act. The eyelids look puffy, especially in the morning, and they don't bounce back the way an allergic reaction would. It often gets dismissed as "they slept funny" or "must be hayfever" for a day or two before the rest of the picture appears.
Then:
- Swelling spreads — first ankles and feet, then genitals (especially scrotal swelling in boys), then the abdomen as ascites builds
- Urine becomes foamy — the protein froths
- Output drops, even though the child is still drinking — fluid is going into tissues rather than through kidneys
- The child feels rotten: tired, irritable, off food
- In severe cases, fluid in the chest (pleural effusion) causes breathlessness
The abdominal swelling can become impressive — a child with massive ascites may put on 2 to 3 kg of fluid in a few days and look 6 months pregnant. That is the picture that lands a family in A&E.
How It's Treated
Prednisolone is the workhorse. NICE CG89 and current paediatric nephrology practice (KDIGO, BAPN guidance) is high-dose prednisolone at 60 mg/m² or 2 mg/kg per day, capped at 60 mg, for 4 to 6 weeks of induction, then tapered to alternate-day dosing for another 4 to 8 weeks before stopping.
Most children with minimal change disease are protein-negative on dipstick within 2 to 4 weeks of starting steroids. Time to remission is itself prognostic — a quick responder usually keeps responding well; a child who takes 8 weeks to clear protein, or doesn't clear at all, gets re-evaluated and often biopsied to look for focal segmental glomerulosclerosis or another cause.
After the first episode, the family is sent home with a plan and dipsticks. The drill:
- Dipstick first morning urine daily during any illness, especially viral upper respiratory infections (the commonest relapse trigger) and after vaccination
- Trace or 1+ for two days running: check with the team
- 2+ or 3+ for three consecutive days: this is a relapse — restart prednisolone per the written protocol
- Acting early shortens relapses and reduces the cumulative steroid dose
When the Steroid Course Itself Becomes a Problem
A single course of prednisolone is usually well tolerated. Repeat courses stack up side effects:
- Weight gain and the moon-face appearance — distressing for school-age children
- Mood changes, irritability, sleep disturbance (often within days of starting)
- Growth velocity slows during prolonged courses
- Increased infection susceptibility
- Long-term: osteopenia, glucose intolerance, cataracts (rare in short courses)
Calcium and vitamin D are given during steroid courses. Bone density may need checking in children on prolonged or frequent treatment.
A child is called a frequent relapser if they have 2 or more relapses in 6 months, or 4 in any 12 months. Steroid-dependent means relapsing on dose reduction or within 2 weeks of stopping. Both groups need a steroid-sparing strategy. Options used in UK paediatric nephrology, in rough order of escalation:
- Levamisole — well tolerated, reduces relapse frequency, often the first add-on
- Mycophenolate mofetil (MMF) — second-line, oral, reasonably well tolerated
- Calcineurin inhibitors (tacrolimus, ciclosporin) — more potent, need blood level monitoring, watch kidney function
- Cyclophosphamide — short course (8–12 weeks), can induce prolonged remission, but fertility considerations in older children
- Rituximab — IV infusions targeting B-cells; increasingly used in frequently relapsing cases, often gives 12+ months relapse-free, reduces cumulative steroid load substantially
The Infection Issues That Matter
Children with active nephrotic syndrome lose immunoglobulins and complement factors in the urine alongside the albumin. They are also usually on steroids. Two infections deserve specific attention:
Bacterial peritonitis. Streptococcus pneumoniae and gram-negatives can seed the ascitic fluid. Fever plus abdominal pain in a child with nephrotic syndrome is an emergency — same-day assessment, blood cultures, and IV antibiotics. It is one of the few situations where a paracentesis to sample ascitic fluid is justified.
Chickenpox in a steroid-treated, non-immune child. Varicella can be severe and occasionally fatal in immunosuppressed children. Any household, classroom, or playgroup exposure needs same-day contact with the nephrology team to discuss varicella zoster immunoglobulin (VZIG) and aciclovir prophylaxis. Check immune status at diagnosis — many children will have had a chickenpox vaccine or natural infection, but some haven't.
Vaccination strategy:- Pneumococcal vaccine (PCV13 + PPV23 boost) — important
- Annual flu vaccine
- Live vaccines (MMR, varicella) avoided during high-dose steroid courses; given in remission off treatment
- Catch up on anything missed at diagnosis once stable
What Long-Term Looks Like
Most children with steroid-responsive minimal change disease grow out of it. Roughly 80% are off all treatment by adolescence; the relapsing pattern becomes less frequent through the school-age years. Long-term kidney function is usually preserved.
The minority who don't respond to steroids — steroid-resistant nephrotic syndrome — are a different problem with different prognosis. Genetic testing (NPHS1, NPHS2, WT1, and other podocyte genes) is part of the workup; some forms are familial and don't respond to immunosuppression at all.
Key Takeaways
Nephrotic syndrome usually shows up first as puffy eyelids that don't go away with the day. The kidney filter is leaking albumin into the urine, water follows out of the bloodstream into tissues, and the child swells. In children, more than 90% of cases are minimal change disease and respond well to oral steroids. Most children relapse at least once. Families learn to dipstick urine at home, recognise the signs early, and call before things get severe. Two infection emergencies to remember: fever with abdominal pain (think bacterial peritonitis), and any chickenpox exposure on steroids.
