Nephrotic syndrome is a clinical state defined by heavy urinary protein loss exceeding 3.5 g per 24 hours in adults (or urine protein/creatinine ratio above 2.0 mg/mg in children), serum albumin below 3.0 g/dL, peripheral edema, and hyperlipidemia. The underlying defect is increased glomerular permeability driven by podocyte injury, immune-complex deposition, or genetic protein mutation.
Nephrotic syndrome (ICD-10: N04) is a glomerular disorder characterized by the triad of heavy proteinuria (>3.5 g/24 h in adults, urine protein/creatinine ratio >2.0 mg/mg in children), hypoalbuminemia (<3.0 g/dL), and peripheral edema, frequently accompanied by hyperlipidemia and a hypercoagulable state. The unifying pathophysiology is loss of the glomerular filtration barrier — specifically podocyte foot-process effacement and slit-diaphragm disruption — which allows albumin and other plasma proteins to spill into urine. In children, more than 85% of cases are minimal change disease, a podocytopathy responsive to corticosteroids. In adults, the spectrum is broader: primary glomerular diseases (membranous nephropathy, focal segmental glomerulosclerosis, minimal change disease, IgA-related variants) account for half of cases, while secondary causes (diabetes mellitus, systemic lupus erythematosus, amyloidosis, hepatitis B and C, HIV, malignancy, and certain drugs) explain the rest.
The key symptoms of Nephrotic Syndrome are: Bilateral lower-extremity pitting edema starting at the ankles, progressing to the calves, thighs, and abdominal wall, often worst at end of day and improved overnight., Periorbital puffiness on waking, frequently the earliest sign in children and mistaken for allergic conjunctivitis., Foamy or frothy urine that persists in the toilet bowl, reflecting heavy proteinuria., Rapid weight gain of 2-10 kg over days to weeks from fluid retention, with tightening of clothing and shoes., Generalized swelling (anasarca) with abdominal distension, scrotal or labial edema, and pleural effusions producing dyspnea in severe cases., Fatigue, malaise, reduced appetite, and easy bruising linked to protein loss, hypoalbuminemia, and altered coagulation., Decreased urine output and dark concentrated urine during marked fluid retention; conversely, polyuria from diuretic therapy once started..
Initial evaluation confirms nephrotic-range proteinuria with a 24-hour urine collection or spot urine protein/creatinine ratio (>3.5 g/24 h or PCR >3.5 mg/mg in adults; >2.0 mg/mg in children), measures serum albumin (<3.0 g/dL confirms hypoalbuminemia), and assesses kidney function (creatinine, eGFR), lipid panel, urinalysis with microscopy (bland sediment supports primary nephrotic disease; red-cell casts shift toward a mixed nephritic-nephrotic picture), and serum complement (C3, C4). Secondary-cause screening is mandatory: HbA1c, hepatitis B surface antigen, hepatitis C antibody, HIV serology, antinuclear antibody, anti-dsDNA, complement, anti-PLA2R antibody (positive in 70-80% of primary membranous nephropathy), serum free light chains and immunofixation (amyloidosis), and age-appropriate cancer screening in adults over 50. In children with classic presentation (age 2-10, normal kidney function, no hematuria, complement normal), empiric corticosteroid therapy is started without biopsy because minimal change disease is overwhelmingly likely. In adults, atypical pediatric cases, and steroid-resistant disease, percutaneous kidney biopsy provides definitive light microscopy, immunofluorescence, and electron microscopy. Imaging (renal ultrasound, Doppler for renal-vein thrombosis) screens for anatomic causes and complications. KDIGO 2021 guideline frames diagnostic workflow.
Outcome depends on histology, age, response to initial therapy, and degree of kidney function at presentation. Pediatric minimal change disease has the best prognosis: 80-90% achieve complete remission with corticosteroids, and even frequent relapsers usually maintain long-term kidney function with appropriate maintenance therapy. Adult minimal change disease responds similarly but with more relapses. Primary FSGS carries a 30-50% risk of progression to end-stage kidney disease over 10 years; partial or complete remission with treatment improves 10-year kidney survival to 80-90% versus 30-50% in unresponsive patients. Primary membranous nephropathy follows a thirds rule: roughly one-third remit spontaneously, one-third have persistent proteinuria with stable kidney function, and one-third progress; modern rituximab-based treatment improves long-term outcomes substantially. Diabetic kidney disease, lupus class V, and amyloidosis follow trajectories of their underlying systemic disease. Across all forms, achieving complete remission (proteinuria <0.3 g/day) is the strongest predictor of long-term kidney preservation, and SGLT2 inhibitors plus RAAS blockade now substantially slow progression even in residual proteinuria.
All patients with nephrotic syndrome require nephrology evaluation. Specialist input is essential for biopsy decisions in adults, choice of immunosuppression, monitoring for treatment toxicity and thromboembolic complications, and recognition of secondary causes that require systemic therapy. Pediatric nephrology manages childhood-onset disease through induction, taper, and relapse.
Find specialists →Children with minimal change disease typically remit within 2-4 weeks of starting prednisolone, with edema resolution and proteinuria clearance. Adult FSGS responses take 8-16 weeks of high-dose steroid therapy. Membranous nephropathy responds more slowly: rituximab effects on anti-PLA2R titres become apparent at 3-6 months and proteinuria clearance often takes 12-24 months. Maintenance immunosuppression and follow-up extend for years even after remission.
Moderate aerobic activity (walking, cycling, swimming) of 150 minutes per week is encouraged once major edema is controlled. Avoid contact sports during active heavy proteinuria due to bleeding risk if anticoagulated. Resume normal activity once stable; resistance training is safe and helps offset corticosteroid-induced muscle loss.
Choose a nephrologist or pediatric nephrologist affiliated with a center that performs percutaneous kidney biopsy, has on-site renal pathology with immunofluorescence and electron microscopy, and a glomerular disease clinic familiar with rituximab, cyclophosphamide, and calcineurin inhibitor regimens. Centers participating in registries (NephCure, Cure GN) typically follow current KDIGO guidance.
Medically reviewed by AIHealz Medical Editorial Board · May 13, 2026
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