What are the causes of nephrotic syndrome?

From the Guidelines

Nephrotic syndrome is primarily caused by damage to the glomeruli, resulting from various diseases and conditions, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and diabetic nephropathy, as well as systemic diseases, medications, infections, and genetic mutations. The most common causes of nephrotic syndrome include:

• Minimal change disease, particularly in children 1
• Focal segmental glomerulosclerosis (FSGS), which can be primary, genetic, secondary, or of undetermined cause 1
• Membranous nephropathy, an autoimmune disease 1
• Diabetic nephropathy, a common cause in adults 1 Other causes of nephrotic syndrome include:
• Systemic diseases like lupus nephritis, amyloidosis, and HIV-associated nephropathy 1
• Certain medications, such as NSAIDs, gold, penicillamine, and some chemotherapy drugs 1
• Infections like hepatitis B, hepatitis C, and malaria 1
• Genetic mutations affecting podocyte proteins, which can cause congenital forms of nephrotic syndrome 1 The underlying pathophysiology of nephrotic syndrome involves damage to the glomerular filtration barrier, particularly the podocytes, leading to increased permeability and allowing proteins to leak into the urine 1. This protein loss results in the characteristic symptoms of nephrotic syndrome: severe proteinuria (>3.5g/day), hypoalbuminemia, edema, and hyperlipidemia. Proper diagnosis requires identifying the specific cause through clinical evaluation, laboratory tests, and often kidney biopsy to guide appropriate treatment strategies 1.

From the Research

Causes of Nephrotic Syndrome

The causes of nephrotic syndrome can be categorized into primary and secondary causes.

• Primary causes in children include:
  • Idiopathic minimal change disease 2, 3
  • Focal segmental glomerulosclerosis (FSGS) 2, 3
• Primary causes in adults include:
  • FSGS 2
  • Membranous nephropathy (MN) 2, 4, 5
• Secondary causes include:
  • Diabetes 2, 5
  • Amyloidosis 2
  • Systemic lupus erythematosus 2, 4, 5
  • Hematologic malignancies 2
  • Infections 2, 4
  • Medication adverse effects 5

Diagnosis and Evaluation

Evaluation for nephrotic syndrome should assess for secondary causes, and may involve:

• Measuring proteinuria and serum albumin and lipid levels 2
• Genetic testing 2, 3
• Kidney biopsy 2, 3, 5
• Testing for serum anti-phospholipase A2 receptor antibodies, which is diagnostic of MN 2, 4