The INCORRECT Statement is C
Statement C is incorrect: Membranous nephropathy is NOT a rare cause of nephrotic syndrome in adults—it is actually one of the most common causes of nephrotic syndrome in adults 1, 2.
Analysis of Each Statement
A) Associated with thrombotic episodes - CORRECT
Membranous nephropathy is indeed strongly associated with thromboembolic complications. The KDIGO 2021 guidelines specifically address anticoagulation strategies for membranous nephropathy patients, with algorithms based on serum albumin levels and thromboembolism risk 3. The hypercoagulable state in nephrotic syndrome can lead to serious complications including pulmonary embolism and venous thromboses 4. Prophylactic anticoagulation should be considered when serum albumin falls below 25 g/L (2.5 g/dL) due to high venous thromboembolism risk 3.
B) Hepatitis B is a secondary cause - CORRECT
Hepatitis B virus is well-established as a secondary cause of membranous nephropathy 3. The KDIGO guidelines recommend screening for hepatitis B (along with HCV, HIV, TB, and syphilis) in clinically appropriate patients with glomerular disease 3. Multiple antigens discovered in membranous nephropathy have been associated with specific secondary causes, with substantial overlap between primary and secondary forms 5.
C) Rare cause of nephrotic syndrome in adults - INCORRECT
This statement is definitively false. Membranous nephropathy is a major etiology and one of the most common causes of nephrotic syndrome in adults 1, 2. The literature consistently identifies it as among the most common adult causes, though less frequent in children 2. The KDIGO 2021 guidelines dedicate an entire chapter to membranous nephropathy, reflecting its clinical significance as one of the "most common adult glomerulonephritides" 3.
D) Can be caused by NSAIDs - CORRECT
Pharmacological agents including NSAIDs are recognized causes of membranous nephropathy. The disease can be linked to drug use in approximately 20% of cases where specific etiology is identified 6. Drug-induced membranous nephropathy represents an important secondary form that clinicians must consider.
E) Candidates for kidney transplantation - CORRECT
Patients with primary membranous nephropathy who progress to end-stage kidney disease are indeed candidates for kidney transplantation. Transplantation is considered optimal therapy for ESKD in membranous nephropathy patients 7. However, clinicians should be aware that recurrence is common post-transplant, particularly in PLA2R-positive cases, and may require protocol biopsies and consideration of rituximab therapy 7.
Clinical Implications
The high prevalence of membranous nephropathy in adults presenting with nephrotic syndrome means:
- Always consider membranous nephropathy in the differential diagnosis of adult nephrotic syndrome
- Screen for secondary causes including hepatitis B, malignancy, and drug exposures
- Assess thromboembolism risk early, particularly when albumin <2.5 g/dL
- Consider PLA2R antibody testing for diagnosis and monitoring (positive in 60-70% of primary cases) 5, 6
- Approximately one-third of patients may achieve spontaneous remission, one-third progress to ESKD, and one-third maintain non-remitting proteinuria 7, 6