From the Guidelines
PLA2R testing is indicated in patients with suspected or confirmed primary membranous nephropathy (MN), particularly before initiating immunosuppressive therapy, to distinguish primary from secondary forms of MN and to monitor disease activity and treatment response. This is based on the latest guidelines from the Kidney Disease: Improving Global Outcomes (KDIGO) 2021, which emphasize the importance of PLA2R antibody testing in the management of MN 1.
Key Indications for PLA2R Testing
- Evaluating patients with nephrotic syndrome and suspected primary MN
- Distinguishing primary from secondary forms of MN, as approximately 70-80% of primary MN cases are PLA2R-antibody positive
- Monitoring disease activity and treatment response, with decreasing antibody levels generally correlating with clinical improvement
- Guiding treatment decisions, including when to taper or discontinue immunosuppressive therapy
- Identifying treatment resistance and the need for alternative therapeutic approaches in patients with persistently high PLA2R antibody levels despite treatment
Clinical Context
In clinical practice, PLA2R testing is particularly useful in situations where kidney biopsy is contraindicated or when trying to differentiate disease relapse from other causes of proteinuria in patients with known membranous nephropathy 1. The test works because PLA2R is the major autoantigen in primary membranous nephropathy, with circulating antibodies forming immune complexes that deposit in the glomerular basement membrane, triggering the characteristic kidney damage seen in this condition.
Monitoring and Follow-Up
According to the KDIGO 2021 guidelines, anti-PLA2R antibodies should be measured at 3–6-month intervals, with the shorter interval being performed in patients with high anti-PLA2R antibodies levels at baseline 1. Changes in anti-PLA2R antibodies levels during follow-up likely add to risk estimation, and disappearance of anti-PLA2R antibodies precedes clinical remission and should lead to refraining from additional therapy.
From the Research
Indications for Checking PLA2R
- PLA2R should be checked in patients with idiopathic membranous nephropathy, as 70%-85% of patients have increased titer of antibodies to the podocyte membrane antigen PLA2R 2.
- Checking PLA2R is also indicated in patients with phospholipase A2 receptor (PLA2R)-associated membranous nephropathy and severe chronic kidney disease, as it can help predict the response to treatment with rituximab 3.
- PLA2R antibody levels can be used to assess the risk of development of nephrotic syndrome in patients with primary membranous nephropathy and non-nephrotic range proteinuria under treatment with inhibitors of the renin-angiotensin system 4.
- Measuring anti-PLA2R levels by immunoassay may be a method to follow and predict response to treatment with rituximab in membranous nephropathy 5.
Clinical Scenarios
- Patients with membranous nephropathy who are being considered for treatment with rituximab should have their PLA2R levels checked to assess their response to treatment 6, 5.
- Patients with non-nephrotic proteinuria at the time of diagnosis should have their PLA2R levels monitored closely, as high levels are associated with an increased risk of development of nephrotic-range proteinuria 4.
- Patients who have achieved remission with rituximab treatment should have their PLA2R levels monitored to detect any potential relapse 5.