Nephrotic Syndrome

Urinary excretion of >3 g protein/day due to a glomerular disorder, plus oedema and hypoalbuminaemia. See nephritic-nephrotic-syndrome.md for the broader nephrotic-vs- nephritic overview.

Epidemiology

Occurs at any age but is more prevalent in children (primarily minimal change disease), mostly aged 1.5–4 years. Under age 8, boys are affected more than girls; equal at older ages.

Most common primary causes: minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy.

Secondary causes account for <10% of childhood cases but >50% of adult cases — most commonly diabetic nephropathy and pre-eclampsia. Amyloidosis (under-recognised) causes ~4%. HIV-associated nephropathy is a form of FSGS occurring in AIDS patients.

Clinical features

Anorexia, malaise, frothy urine (from high protein concentration). Fluid retention may cause dyspnoea (pleural effusion/laryngeal oedema), arthralgia (hydrarthrosis), abdominal pain (ascites, or mesenteric oedema in children), and peripheral oedema.

Complications

Complication	Contributing factor(s)
Oedema (± ascites, pleural effusions)	Generalised capillary leak from hypoalbuminaemia; possibly renal sodium retention
Infection (especially cellulitis; spontaneous bacterial peritonitis in 2–6%)	Possibly loss of opsonins/immunoglobulins
Anaemia	Loss of erythropoietin and transferrin
Thyroid function changes	Loss of thyroid-binding globulin
Hypercoagulability/thromboembolism (renal vein thrombosis, PE — up to 5% of children, 40% of adults)	Loss of antithrombin III; increased hepatic clotting-factor synthesis; platelet abnormalities; hyperviscosity
Protein undernutrition in children (brittle hair/nails, alopecia, stunted growth)	Protein loss; decreased hepatic production; reduced oral intake
Dyslipidaemia	Increased hepatic lipoprotein synthesis
Coronary artery disease (adults)	Dyslipidaemia-driven atherosclerosis
Hypertension (adults)	Renal sodium retention
Bone disorder	Corticosteroid use; vitamin D deficiency (loss of vitamin D binding protein)
CKD	Possibly hypovolaemia, interstitial oedema, NSAID use
Proximal tubular dysfunction (acquired Fanconi syndrome)	Toxic effect of reabsorbed protein on tubular cells

Diagnosis

• Urine spot protein:creatinine ratio ≥3, or proteinuria ≥3 g/24h (normal is <150 mg/day)
• Serum albumin often <25 g/L; total cholesterol and triglycerides typically raised
• Secondary-cause screening: glucose/HbA1c, ANA, hepatitis B/C serology, serum/urine protein electrophoresis, cryoglobulins, rheumatoid factor, syphilis serology, HIV antibody, complement (C3, C4)
• Renal biopsy is indicated in adults to diagnose idiopathic nephrotic syndrome

Management

• Treat the underlying cause
• ACEi/ARB for proteinuria (SGLT2 inhibitors are now an additional consideration in appropriate patients — see chronic-kidney-disease.md)
• Sodium restriction for oedema; diuretics for significant fluid overload
• Statins
• Rarely, nephrectomy (or renal artery embolisation as a less invasive alternative) for severe nephrotic syndrome with persistent hypoalbuminaemia