Nephrotic syndrome has a way of appearing suddenly and dramatically. A child who had puffy eyes at breakfast has a face that parents barely recognise by the afternoon. The abdomen swells, the legs become oedematous, and a parent who has never heard the word nephrotic is sitting in A&E trying to take in information about protein and kidneys while watching their child look very unwell.
Once the initial diagnosis and treatment have happened, nephrotic syndrome becomes a condition that families manage largely at home – learning to read urine dipstick results, recognising a relapse early, and knowing when to go straight to hospital. That management literacy is genuinely empowering. It also reduces the number of relapses that become medical emergencies.
Healthbooq (healthbooq.com/apps/healthbooq-kids) covers kidney and urinary conditions in children.
What Is Happening in the Kidney
The kidney's glomeruli are tiny filtering units that should allow water and small molecules to pass into the urine while retaining proteins in the blood. In nephrotic syndrome, the glomerular filtration barrier becomes abnormally permeable, allowing protein – mainly albumin – to leak out in large quantities.
The loss of albumin from the blood has downstream consequences. Albumin normally holds fluid inside blood vessels by osmotic pressure; when albumin levels fall, fluid leaks out of blood vessels into body tissues, causing oedema. The liver compensates by making more lipoprotein, causing high blood lipid levels (hyperlipidaemia). The combination of protein in urine, low blood albumin, oedema, and high lipids defines the nephrotic syndrome.
In children, over 90% of cases have minimal change disease (MCD) as the underlying pathology on biopsy: a condition in which the glomeruli appear normal under light microscopy but have characteristic changes on electron microscopy. MCD is extremely steroid-responsive. The reason MCD occurs is not fully understood; current understanding implicates T-cell dysfunction affecting the glomerular podocytes.
Who Gets It
Nephrotic syndrome affects approximately 2-7 per 100,000 children per year. It is most common between 2 and 5 years of age. Boys are more frequently affected than girls (ratio approximately 2:1) in childhood, though this sex difference narrows after puberty. There is a higher incidence in children of South Asian origin.
Signs and Symptoms
Swelling around the eyes (periorbital oedema) is often the first sign and is most noticeable in the morning. It can be dismissed as a restless night or an allergic reaction. Oedema progressively spreads to the ankles, legs, genitals, and abdomen (ascites). In severe cases, fluid accumulates in the pleural space (pleural effusion), causing breathlessness.
Urine becomes foamy due to the high protein content. Children often have reduced urine output despite normal fluid intake (because fluid is leaking into tissues rather than passing through the kidneys). Lethargy, irritability, and reduced appetite accompany significant fluid retention.
Treatment
Prednisolone (oral corticosteroid) is first-line treatment. NICE CG89 recommends high-dose prednisolone at 2mg/kg/day (maximum 60mg) for the initial episode, continuing for 4-6 weeks, then tapering. Most children with minimal change disease are in remission (urine protein-negative or trace on dipstick) within 2-4 weeks.
During a relapse, parents are trained to check urine protein with a dipstick daily when a child has a cold or illness (common relapse triggers) and to restart prednisolone promptly when protein ++ or +++ appears on the dipstick, according to their nephrologist's protocol.
Steroid side effects with repeated courses include growth suppression, weight gain, behavioural changes, increased infection susceptibility, and osteoporosis with very prolonged use. Calcium and vitamin D supplements are given during steroid courses. The psychological impact of repeated steroid courses on a growing child is significant.
Frequently relapsing or steroid-dependent nephrotic syndrome (defined as two or more relapses within 6 months, or relapse on dose reduction) requires additional immunosuppression. Options include levamisole, cyclophosphamide, mycophenolate mofetil (MMF), calcineurin inhibitors (tacrolimus, ciclosporin), and rituximab (an anti-CD20 biologic). Rituximab, developed by researchers at UCSF and used extensively in paediatric nephrology, can induce prolonged remission in many frequently relapsing cases and reduce cumulative steroid exposure.
Infection Risk
Children with nephrotic syndrome are at significantly increased risk of serious bacterial infections, particularly pneumococcal peritonitis and septicaemia. This is due to loss of immunoglobulins and complement factors in the urine, combined with steroid-related immunosuppression. Fever in a child with nephrotic syndrome, particularly with abdominal pain, requires urgent assessment. Pneumococcal vaccination (and catch-up vaccination) is important. Varicella is a particular concern in steroid-treated children: exposure to chickenpox in a non-immune child on steroids requires prompt assessment for varicella immunoglobulin (VZIG).
Key Takeaways
Nephrotic syndrome is a kidney condition in which the glomerular filtration barrier becomes abnormally leaky, allowing large amounts of protein (mainly albumin) to be lost in the urine. It causes significant oedema (swelling), most visibly around the eyes and ankles. It is most common in children aged 2-5 years. Over 90% of childhood nephrotic syndrome responds to steroids (prednisolone), and the majority of cases are minimal change disease on kidney biopsy. However, most children relapse at least once, and frequent relapsers need additional immunosuppressive agents. Parents are trained to monitor urine protein at home with dipstick tests and to initiate steroid treatment early during relapses.
