Nephrotic syndrome

Definition

Nephrotic syndrome is characterized by heavy glomerular proteinuria in the nephrotic range (> 3.5 g/day; some definitions use ≥ 3 g/day), hypoalbuminemia and edema; hyperlipidemia and lipiduria are usually also present. It is not a single disease but a syndrome caused by various glomerulopathies.

Occurrence & epidemiology

Nephrotic syndrome occurs at any age but is more common in children (mean age at diagnosis 5–6 years, mostly minimal change disease). Below 8 years, boys are affected more often than girls; at older ages both sexes equally. Congenital forms present in the first year of life.

Aetiopathogenesis

• Primary causes: minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy; less often membranoproliferative glomerulonephritis or IgA nephropathy
• Secondary causes (more common in adults): diabetic nephropathy, systemic lupus erythematosus, amyloidosis, preeclampsia, cancer (carcinomas, lymphomas, myeloma), infections (hepatitis B and C, HIV, syphilis, malaria), drugs and substances (e.g. NSAIDs, heroin), severe obesity, genetic syndromes

Pathophysiologically, the endothelial cells, glomerular basement membrane or podocytes that normally retain proteins by size and charge are damaged. Besides albumin, antibodies, opsonins, antithrombin III, transferrin and binding proteins for hormones and vitamin D are lost in the urine, which explains the complications.

Clinical features

Symptoms and complications

Leading symptoms are edema (peripheral edema, plus ascites and pleural effusions), frothy urine, anorexia and malaise. Effusions may cause dyspnea, joint symptoms or abdominal pain; white transverse lines on the fingernails (Muehrcke lines) may appear.

• Thromboembolism, especially renal vein thrombosis and pulmonary embolism (loss of antithrombin III, increased hepatic synthesis of clotting factors)
• Infections such as cellulitis and spontaneous bacterial peritonitis (loss of antibodies and opsonins)
• Dyslipidemia with increased atherosclerotic risk, hypertension, anemia, vitamin D deficiency and chronic kidney disease

Diagnosis

• Proteinuria: protein-to-creatinine ratio in a spot urine or 24-hour urine collection (normal < 150 mg/24 h)
• Urine sediment: lipiduria with oval fat bodies and fatty casts; cholesterol shows a Maltese cross pattern under polarized light
• Blood: serum albumin often < 2.5 g/dL (25 g/L), elevated total cholesterol and triglycerides, creatinine and urea depending on kidney function
• Search for secondary causes depending on the clinical context: HbA1c, antinuclear antibodies, hepatitis B and C serology, HIV and syphilis serology, serum and urine protein electrophoresis, cryoglobulins, complement C3 and C4
• Kidney biopsy: in adults with an unclear cause to diagnose the underlying glomerulopathy; in children with a typical presentation, minimal change disease is usually presumed

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Overview of Nephrotic Syndrome
2. MSD Manual Professional: Proteinuria

Cross-references