From the Guidelines
PLA2R (phospholipase A2 receptor) is a crucial biomarker in diagnosing and monitoring primary membranous nephropathy, guiding treatment decisions and predicting disease outcomes. The presence of anti-PLA2R antibodies, found in approximately 70-80% of patients with primary membranous nephropathy, is a valuable diagnostic tool to distinguish primary from secondary forms of the disease 1. Testing for PLA2R antibodies can be done through blood tests that measure antibody levels, which correlate with disease activity, with higher levels indicating active disease and decreasing levels suggesting response to treatment 1.
Treatment Decisions
The levels of anti-PLA2R antibodies help guide treatment decisions, as patients with positive antibodies may require immunosuppressive therapy such as rituximab, cyclophosphamide, or calcineurin inhibitors 1. According to the KDIGO 2021 guideline, for patients with MN and at least one risk factor for disease progression, consider using rituximab or cyclophosphamide and alternate month glucocorticoids for 6 months, or tacrolimus-based therapy for ≥ 6 months, depending on the estimate of risk 1.
Monitoring and Outcome Prediction
Regular monitoring of PLA2R antibody levels during treatment provides valuable information about treatment effectiveness and can help determine when therapy might be reduced or discontinued 1. The presence and levels of these antibodies can also help predict disease outcomes and the risk of progression to kidney failure. A decline in anti-PLA2R antibody levels precedes and predicts changes in clinical parameters, such as proteinuria, allowing for the limitation of immunosuppressive treatment to the shortest duration necessary to achieve an immunologic remission 1.
Key Considerations
- Immunosuppressive Therapy: Should be considered when at least one risk factor for disease progression is present or when serious complications of nephrotic syndrome have occurred.
- Monitoring: Longitudinal monitoring of anti-PLA2R antibody levels after starting therapy may be useful for evaluating treatment response and guiding adjustments to therapy.
- Treatment Adjustment: Persistence of anti-PLA2R antibodies should lead to continued therapy or a change to another agent, while disappearance of these antibodies (immunologic remission) can indicate the limitation of further immunosuppression.
From the Research
PLA2R Overview
- PLA2R (phospholipase A2 receptor) is an antigen associated with primary membranous nephropathy (MN), a kidney-specific autoimmune disease 2, 3, 4, 5, 6
- MN is characterized by the diffuse thickening of the glomerular basement membrane secondary to immune complex deposition, leading to nephrotic syndrome (NS) 2
PLA2R Antibodies and Membranous Nephropathy
- Approximately 70-85% of patients with idiopathic membranous nephropathy have increased titers of antibodies to PLA2R 3
- The presence of anti-PLA2R antibodies is a key factor in the pathogenesis of MN, and their levels can be used to predict disease activity and response to treatment 5, 6
- High levels of PLA2R antibodies (>150 RU/ml) are associated with more severe disease and poorer prognosis 6
Treatment of PLA2R-Associated Membranous Nephropathy
- Standard therapy for MN includes immunosuppressive agents such as rituximab, cyclophosphamide, and calcineurin inhibitors, often combined with corticosteroids 2, 3, 4, 6
- Rituximab, a B-cell depleting agent, has been shown to be effective in inducing remission in patients with MN, particularly those with high levels of PLA2R antibodies 4, 5
- Plasmapheresis, a procedure that removes antibodies from the blood, has also been used to treat patients with MN who are refractory to standard therapy or have high levels of PLA2R antibodies 3