From the Guidelines
Membranous glomerulonephritis (MGN) is primarily caused by autoantibodies against podocyte antigens, with the phospholipase A2 receptor (PLA2R) being the most common target antigen, found in approximately 70-80% of patients with primary membranous nephropathy, as stated in the KDIGO 2021 clinical practice guideline for the management of glomerular diseases 1. The etiologies of membranous glomerulonephritis can be broadly categorized as primary (idiopathic) or secondary causes. Primary membranous glomerulonephritis, now known as primary membranous nephropathy, accounts for about 75% of cases. Another target antigen is thrombospondin type-1 domain-containing 7A (THSD7A) in about 3-5% of cases. Secondary causes of membranous glomerulonephritis include:
- Autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis)
- Infections (hepatitis B and C, syphilis, malaria)
- Malignancies (solid tumors like lung, colon, and breast cancer, as well as hematologic malignancies)
- Medications or toxins (gold, penicillamine, NSAIDs, mercury) The pathophysiology involves the formation of immune complexes that deposit in the glomerular basement membrane, activating complement and causing podocyte injury, which leads to proteinuria. In patients diagnosed with membranous glomerulonephritis, it's essential to conduct a thorough evaluation to distinguish between primary and secondary forms, as treatment approaches differ significantly depending on the underlying cause, as emphasized by the Mayo Clinic/Renal Pathology Society consensus report on pathologic classification, diagnosis, and reporting of GN 1.
From the Research
Etiologies of Membranous Glomerulonephritis
The etiologies of membranous glomerulonephritis can be classified into two main categories: idiopathic and secondary.
- Idiopathic membranous glomerulonephritis is the most common form, accounting for approximately 80% of cases 2.
- Secondary membranous glomerulonephritis is associated with various underlying conditions, including:
Clinical Characteristics
The clinical characteristics of membranous glomerulonephritis vary depending on the underlying etiology.
- Idiopathic membranous glomerulonephritis often presents with proteinuria, nephrotic syndrome, hypertension, and hematuria 4.
- Secondary membranous glomerulonephritis may present with additional symptoms related to the underlying condition, such as systemic lupus erythematosus or hepatitis B infection 4.
Histological and Serological Features
Histological and serological features can help differentiate between primary and secondary membranous glomerulonephritis.
- The presence of specific autoantibodies, such as those against the phospholipase A2 receptor (PLA2R), can be a useful biomarker for idiopathic membranous glomerulonephritis 2, 5.
- Histological clues, such as the presence of mesangial and/or subendothelial deposits, tubuloreticular inclusions, and full house immunofluorescence, can suggest secondary membranous glomerulonephritis 3, 6.