Nephrotic Syndrome
Nephrotic syndrome is a kidney condition in which damaged filtering units allow large amounts of protein to leak from the blood into the urine. It is one of the most common kidney diseases in children, and while it often requires long-term management, many children do very well with treatment. Our team has extensive experience managing all forms of nephrotic syndrome, from a first episode through complex, relapsing disease.
What Is Nephrotic Syndrome?
The kidneys contain millions of tiny filtering units called glomeruli. In nephrotic syndrome, these filters are damaged and become too “leaky,” allowing protein — especially albumin — to pass into the urine. When protein levels in the blood drop too low, fluid shifts out of the bloodstream and into body tissues, causing swelling (edema). The classic features of nephrotic syndrome are heavy protein in the urine, low protein in the blood, and swelling.
Causes
In most children, nephrotic syndrome has no identifiable external cause and is called idiopathic (or primary) nephrotic syndrome. The most common underlying types are:
- Minimal Change Disease (MCD) – the most common cause in young children; the kidneys look nearly normal under a microscope but don’t function properly
- Focal Segmental Glomerulosclerosis (FSGS) – some of the kidney’s glomeruli become scarred; more common in older children and teens, and more likely to be steroid-resistant
- Membranous Nephropathy – less common in children; may be associated with autoimmune conditions
In some cases, nephrotic syndrome is secondary to another condition such as lupus, infection, or a genetic disorder.
Signs and Symptoms
The hallmark symptom of nephrotic syndrome is swelling, which often appears first as puffiness around the eyes in the morning. Other signs include:
- Swelling in the ankles, feet, legs, or belly
- Foamy or frothy urine (caused by protein)
- Decreased urination
- Fatigue and loss of appetite
- Weight gain from fluid retention
These symptoms often appear suddenly and can be alarming for families. If you notice these signs in your child, contact your pediatrician promptly.
Diagnosis
Diagnosis is typically confirmed through:
- Urine tests – to measure protein levels (a urine protein-to-creatinine ratio is commonly used)
- Blood tests – to check albumin, cholesterol, kidney function, and other markers
- Kidney biopsy – performed when the diagnosis is uncertain, when a child does not respond to steroids, or in older children where FSGS is more likely; biopsies are performed on-site in our clinic
Treatment
The first-line treatment for most children with nephrotic syndrome is corticosteroids (prednisone). Approximately 85–90% of young children respond well to steroids and achieve remission within 4–6 weeks. However, relapses are common — 70–80% of children who initially respond will experience at least one relapse.
For children who relapse frequently or become dependent on steroids, additional medications may be used to reduce steroid exposure and maintain remission. These include:
- Mycophenolate mofetil (MMF)
- Calcineurin inhibitors (tacrolimus or cyclosporine)
- Cyclophosphamide
- Rituximab – an antibody-based therapy increasingly used for steroid-dependent or frequently relapsing disease
- Obinutuzumab
Children with steroid-resistant nephrotic syndrome require additional evaluation, including kidney biopsy and genetic testing, to guide individualized treatment. Our team offers genetic testing panels that cover more than two dozen genes associated with nephrotic syndrome and FSGS.
Living With Nephrotic Syndrome
Nephrotic syndrome is a condition that many children manage over the long term. During active disease or relapses, children may need temporary dietary adjustments (such as reduced salt intake), monitoring at home using urine dipsticks, and prompt contact with the care team when relapses are suspected. Between relapses, most children can participate in normal activities including school and sports.
Care at Rady Children’s
Children with nephrotic syndrome are seen in our General Nephrology and CKD Clinic, where urine studies and lab draws are performed on-site at every visit. Our team includes specialists experienced in both common and rare presentations of nephrotic syndrome, including steroid-resistant disease and complex genetic forms. We work closely with families to develop a management plan that fits their child’s specific diagnosis and their family’s needs.