From the Guidelines
PLA2R is a crucial biomarker in the diagnosis and monitoring of primary membranous nephropathy (PMN), and its antibody levels should be regularly monitored every 3-6 months to assess therapeutic response and detect early signs of relapse. The use of anti-PLA2R antibody titers has been validated as a useful clinical tool in the prognosis of MN, with changes in antibody levels preceding and predicting changes in proteinuria and long-term prognosis 1. High antibody levels typically correlate with disease severity and risk of progression, while decreasing levels often indicate response to immunosuppressive therapy.
Key Points
- Testing for anti-PLA2R antibodies helps differentiate primary from secondary forms of membranous nephropathy, which is crucial for treatment decisions.
- The likelihood of spontaneous remission is inversely related to the degree of detectable antibody at the time of diagnosis, with spontaneous remission rates consistently highest among patients with low anti-PLA2R antibody levels 1.
- The trajectory of anti-PLA2R antibody levels over the course of several serial measurements is more important than a single autoantibody measurement, with increasing levels conferring greater risk of prolonged disease than decreasing levels 1.
- For patients diagnosed with PLA2R-positive membranous nephropathy, 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, with rituximab or cyclophosphamide and alternate month glucocorticoids being recommended treatment options 1.
Treatment and Monitoring
- Longitudinal monitoring of anti-PLA2R antibody levels after starting therapy may be useful for evaluating treatment response in patients with MN, and can be used to guide adjustments to therapy 1.
- In patients with MN and initial relapse of the nephrotic syndrome after therapy, the initial therapy can be repeated or treatment may be switched to rituximab in those initially treated with calcineurin inhibitors or cyclophosphamide 1.
- Prophylactic anticoagulant therapy in patients with MN and nephrotic syndrome should be based on an estimate of the risk of thromboembolic events, with regular monitoring of anti-PLA2R antibody levels and clinical parameters being essential for guiding treatment decisions 1.
From the Research
PLA2R-Associated Membranous Nephropathy
- PLA2R-associated membranous nephropathy is a common cause of nephrotic syndrome in adults, characterized by the presence of autoantibodies against the phospholipase A2 receptor (PLA2R) 2, 3.
- The disease can be primary or secondary, with secondary forms often associated with malignancy, infection, or autoimmune disease 4.
Treatment with Rituximab
- Rituximab, a B-cell depleting agent, has emerged as a safe and effective treatment for PLA2R-associated membranous nephropathy, inducing remission in approximately two-thirds of treated patients 2, 5, 3, 6.
- The treatment regimen typically consists of weekly infusions of rituximab, with the possibility of repeated courses to achieve immunological remission 2, 5.
- Rituximab has been shown to be effective in patients with stage 4 or 5 chronic kidney disease, as well as in those with malignancy-associated membranous nephropathy 2, 5.
Predictive Factors and Outcomes
- The urinary albumin-to-protein ratio before treatment has been identified as a predictive factor of renal response to rituximab 2.
- Immunological remission, characterized by the depletion of anti-PLA2R autoantibodies, is associated with a good clinical outcome and can be used as a biomarker to predict response to treatment 3.
- Patients who achieve complete or partial remission after rituximab treatment tend to have stable renal function and improved clinical parameters, such as reduced proteinuria and increased serum albumin levels 2, 5.