What are the etiologies for Nephrotic Syndrome (NS)?

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From the Guidelines

Nephrotic syndrome is caused by several distinct etiologies, including primary causes such as minimal change disease, focal segmental glomerulosclerosis (FSGS), membranous nephropathy, and membranoproliferative glomerulonephritis, as well as secondary causes like diabetes mellitus, systemic lupus erythematosus, and infections, as noted in the 2023 study by 1.

Primary Causes

  • Minimal change disease: most common in children
  • Focal segmental glomerulosclerosis (FSGS): can be primary or secondary, with secondary causes including viral injury, medication-related injury, or adaptive changes, as described in the 2023 study by 1
  • Membranous nephropathy
  • Membranoproliferative glomerulonephritis

Secondary Causes

  • Diabetes mellitus: leading cause in adults
  • Systemic lupus erythematosus
  • Amyloidosis
  • Infections: HIV, hepatitis B and C, malaria
  • Medications: NSAIDs, gold, penicillamine
  • Malignancies: particularly lymphomas and solid tumors
  • Genetic disorders: congenital nephrotic syndrome

Pathophysiology and Treatment

The pathophysiology involves damage to podocytes and the glomerular basement membrane, leading to increased permeability and characteristic findings of heavy proteinuria, hypoalbuminemia, hyperlipidemia, and edema, as discussed in the 2007 study by 1. Treatment depends on identifying and addressing the underlying cause, with supportive measures including ACE inhibitors or ARBs to reduce proteinuria, diuretics for edema management, statins for hyperlipidemia, and immunosuppressive therapy for certain primary glomerular diseases, as recommended in the 2023 study by 1. Prompt diagnosis and management are essential to prevent complications like thromboembolism, infections, and progression to end-stage renal disease.

Recent Guidelines

The 2023 study by 1 provides guidance on the management of glomerular diseases, including the use of glucocorticoids and immunosuppressive therapy for patients with idiopathic immune complex glomerulonephritis. The 2023 study by 1 also proposes a novel classification system for FSGS, dividing patients into four subclasses: primary FSGS, genetic FSGS, secondary FSGS, and FSGS of undetermined cause.

Key Considerations

  • Identifying and addressing the underlying cause of nephrotic syndrome is crucial for effective treatment, as noted in the 2014 study by 1
  • Supportive measures, such as ACE inhibitors or ARBs, diuretics, and statins, can help manage symptoms and prevent complications, as discussed in the 2019 study by 1
  • Immunosuppressive therapy may be necessary for certain primary glomerular diseases, but its use should be carefully considered due to potential side effects, as described in the 2014 study by 1

From the Research

Etiologies of Nephrotic Syndrome

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

  • Primary causes are diseases specific to the kidneys, while secondary causes are due to systemic disorders.

Primary Causes

Some of the primary causes of nephrotic syndrome include:

  • Minimal change disease, which is the most common cause in children 2, 3, 4
  • Membranous nephropathy, which is the most common cause in white adults 2, 3, 5
  • Focal segmental glomerulosclerosis (FSGS), which is the most common cause in populations of African ancestry and also common in adults 2, 3, 4

Secondary Causes

Secondary causes of nephrotic syndrome include:

  • Diabetic nephropathy, which is the most common multisystem disease that can cause nephrotic syndrome 2
  • Systemic lupus erythematosus 2, 3, 5
  • Amyloidosis 2, 3
  • Hematologic malignancies 3
  • Infections 3

Diagnosis and Evaluation

Diagnosis and evaluation of nephrotic syndrome involve documenting proteinuria and hypoalbuminemia, and assessing for secondary causes 2, 3, 5. A renal biopsy is often performed to establish the underlying glomerular disease responsible for the syndrome 2, 3, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diagnosis and Management of Nephrotic Syndrome in Adults.

American family physician, 2016

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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