What are the indications for checking Phospholipase A2 Receptor (PLA2R)?

From the Guidelines

PLA2R (phospholipase A2 receptor) antibody testing is primarily indicated for patients with suspected or confirmed primary membranous nephropathy (MN), particularly those with heavy proteinuria (>3.5g/day), normal kidney function, and no evidence of secondary causes, as stated in the 2023 guideline 1. Testing should be considered in adults presenting with nephrotic syndrome, where PLA2R testing can help differentiate primary from secondary membranous nephropathy, as approximately 70-80% of primary MN cases are PLA2R-antibody positive 1. The test is especially valuable in patients where kidney biopsy is contraindicated or when biopsy results are inconclusive. Additionally, PLA2R antibody levels can be used to monitor disease activity, predict response to immunosuppressive therapy, and assess risk of relapse, with serial measurements guiding therapeutic decisions, as declining antibody levels often precede clinical remission 1. PLA2R testing is also beneficial in transplant recipients with recurrent proteinuria to evaluate for disease recurrence, based on the autoimmune nature of primary MN, where antibodies target the PLA2R antigen on podocytes, leading to immune complex formation and subsequent proteinuria 1. Some key points to consider when interpreting PLA2R antibody test results include:

• A positive test result indicates immunologically active MN, while a negative result may suggest secondary MN or other causes of nephrotic syndrome 1.
• Serial measurements of PLA2R antibody levels can help monitor disease activity and response to treatment, with decreasing levels often preceding clinical remission 1.
• The test can also be used to assess risk of relapse and guide adjustments to therapy, particularly in patients with persistent proteinuria or declining kidney function 1.
• In patients with suspected MN, a kidney biopsy may still be necessary to confirm the diagnosis and rule out other causes of nephrotic syndrome, especially if the PLA2R antibody test result is negative or inconclusive 1. Overall, PLA2R antibody testing is a valuable tool in the diagnosis and management of primary membranous nephropathy, and should be considered in patients with suspected or confirmed disease, particularly those with heavy proteinuria and normal kidney function.

From the Research

Indications to Check PLA2R

The following are indications to check PLA2R:

• Idiopathic membranous nephropathy (IMN) diagnosis and monitoring 2, 3, 4, 5, 6
• Nephrotic syndrome (NS) diagnosis and monitoring 2, 3, 4, 5, 6
• Non-nephrotic range proteinuria under treatment with inhibitors of the renin-angiotensin system 3
• Primary membranous nephropathy (PMN) diagnosis and monitoring 2, 3, 4, 5, 6
• PLA2R-associated membranous nephropathy and severe chronic kidney disease (CKD) diagnosis and monitoring 6
• Assessment of risk for development of nephrotic proteinuria in patients with non-nephrotic proteinuria at the time of diagnosis 3
• Monitoring of response to treatment with rituximab in membranous nephropathy 2, 4, 6

Clinical Scenarios

PLA2R should be checked in the following clinical scenarios:

• Patients with IMN or PMN who are not responding to standard therapy 2
• Patients with NS or non-nephrotic range proteinuria who are at risk of developing nephrotic proteinuria 3
• Patients with PLA2R-associated membranous nephropathy and severe CKD who are being considered for treatment with rituximab 6
• Patients with primary MN who are being considered for a non-invasive diagnostic test instead of a kidney biopsy 5