What are the causes of nephrotic syndrome?

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From the Guidelines

Nephrotic syndrome is primarily caused by damage to the glomeruli, with the most common causes including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and diabetic nephropathy, as outlined in the 2021 KDIGO clinical practice guideline for the management of glomerular diseases 1.

Causes of Nephrotic Syndrome

The causes of nephrotic syndrome can be categorized into primary and secondary glomerular diseases. Primary glomerular diseases include:

  • Minimal change disease, which is the most common cause in children
  • Focal segmental glomerulosclerosis (FSGS)
  • Membranous nephropathy Secondary glomerular diseases include:
  • Diabetic nephropathy, which is a common cause in adults
  • Systemic diseases such as lupus nephritis, amyloidosis, and HIV-associated nephropathy
  • Certain medications like NSAIDs, gold, penicillamine, and some chemotherapy drugs
  • Infections including hepatitis B, hepatitis C, and malaria
  • Genetic mutations affecting podocyte proteins, which can cause congenital forms of nephrotic syndrome

Pathophysiology

The fundamental pathophysiology of nephrotic syndrome involves damage to the glomerular filtration barrier, particularly the podocytes and their slit diaphragms, which normally prevent protein leakage 1. This damage allows proteins, especially albumin, to escape into the urine, resulting in the classic symptoms of proteinuria, hypoalbuminemia, edema, and hyperlipidemia that characterize nephrotic syndrome.

Management

The management of nephrotic syndrome depends on the underlying cause and may involve immunosuppressive therapy, supportive care, and treatment of any underlying systemic disease, as discussed in the KDIGO guideline 1. It is essential to accurately diagnose the cause of nephrotic syndrome to provide appropriate treatment and improve patient outcomes.

From the Research

Causes of Nephrotic Syndrome

The causes of nephrotic syndrome can be primary or secondary. Primary causes include:

  • Idiopathic minimal change disease, which is the most common cause in children 2, 3
  • Focal segmental glomerulosclerosis (FSGS), which is a common cause in both children and adults 2, 4, 3
  • Membranous nephropathy (MN), which is a common cause in adults 2, 5, 6

Secondary Causes

Secondary causes of nephrotic syndrome include:

  • Diabetes mellitus 2, 5, 6
  • Systemic lupus erythematosus 2, 5, 3
  • Amyloidosis 2
  • Hematologic malignancies 2
  • Infections 2
  • Gene mutations 3

Diagnosis and Evaluation

Diagnosis and evaluation of nephrotic syndrome involve:

  • Measuring proteinuria and serum albumin and lipid levels 2
  • Assessing for secondary causes 2
  • Renal biopsy, which is often recommended, especially in adults with suspected underlying systemic disease 2, 5, 6
  • Genetic testing, which may be warranted in children who do not respond to steroid treatment 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Nephrotic Syndrome.

Pediatric clinics of North America, 2019

Research

Diagnosis and Management of Nephrotic Syndrome in Adults.

American family physician, 2016

Research

Nephrotic Syndrome.

Primary care, 2020

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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