From the Guidelines
Membranous nephropathy is related to abnormal inflammatory responses, characterized by immune complex deposition in the glomerular basement membrane, triggering inflammation that damages the filtering structures of the kidneys. This kidney disorder involves autoantibodies (particularly anti-PLA2R antibodies) that target podocyte antigens, creating immune complexes that activate complement and initiate inflammatory cascades, as discussed in the KDIGO 2021 clinical practice guideline for the management of glomerular diseases 1. The primary form of membranous nephropathy is an autoimmune disease, and secondary forms can be associated with infections, autoimmune diseases, medications, or malignancies, but the common pathway involves immune-mediated inflammation 1.
Some key points to consider in the management of membranous nephropathy include:
- The disease is not linked to chromosomal abnormalities as a primary cause
- Inflammation is central to its pathophysiology and progression
- The disorder has some systemic manifestations like proteinuria and edema, but it is fundamentally a kidney-specific disorder rather than a systemic abnormality
- Risk assessment is crucial, and patients can be categorized into low-risk, moderate-risk, high-risk, and very high-risk groups based on clinical and laboratory criteria, including proteinuria levels, serum albumin, and eGFR 1
- Treatment strategies, including immunosuppression and supportive therapy, should be guided by the patient's risk category and response to therapy, with ongoing research aiming to improve therapy and make it more mechanism-directed 1
Overall, the pathophysiological mechanism of membranous nephropathy is closely tied to abnormal inflammatory responses, and its management should prioritize a comprehensive approach that addresses the underlying immune-mediated processes.
From the Research
Pathophysiological Mechanism of Membranous Nephropathy
The pathophysiological mechanism of membranous nephropathy is complex and involves the formation of immune complexes in the subepithelial space of the glomerulus, leading to complement activation and glomerular damage 2, 3, 4, 5. The exact mechanism is still not fully understood, but several hypotheses have been proposed, including the formation of preformed immune complexes, in situ immune-complex formation, and autoantibody against podocyte membrane antigen 2.
Role of Autoantibodies and Antigens
Autoantibodies against specific podocyte antigens, such as the phospholipase A2 receptor (PLA2R1) and thrombospondin type-1 domain-containing 7A (THSD7A), play a crucial role in the pathogenesis of membranous nephropathy 3, 5. The formation of antibodies against PLA2R1 is more common, accounting for 70-80% of idiopathic membranous nephropathy cases 5.
Involvement of Inflammation and Immune Response
While membranous nephropathy is considered a non-inflammatory disease, there is evidence to suggest that inflammation and immune response may play a role in its pathogenesis 4, 5. The exposure of PLA2R1 and other antigens may trigger an immune response, leading to the formation of autoantibodies and immune complexes 5.
Key Features of Membranous Nephropathy
Some key features of membranous nephropathy include:
- Formation of immune complexes in the subepithelial space of the glomerulus
- Complement activation and glomerular damage
- Autoantibodies against specific podocyte antigens, such as PLA2R1 and THSD7A
- Non-inflammatory disease, but with possible involvement of inflammation and immune response
- Characterized by nephrotic syndrome and associated complications 2, 3, 4, 5, 6
Systemic Abnormalities and Chromosome Abnormality
There is no direct evidence to suggest that membranous nephropathy is linked to chromosome abnormality or systemic abnormalities as a primary cause 2, 3, 4, 5, 6. However, secondary causes of membranous nephropathy may include autoimmune diseases, infection, drugs, and malignancy 2, 3.