Noninvasive Diagnosis of PLA2R-Associated Membranous Nephropathy: A Validation Study
Shane A Bobart1,2, Heedeok Han3, Shahrzad Tehranian1
1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
Background And Objectives:
Kidney biopsy is the current gold standard to diagnose membranous nephropathy. Approximately 70%-80% of patients with primary membranous nephropathy have circulating anti-phospholipase A2 receptor antibodies. We previously demonstrated that in proteinuric patients with preserved eGFR and absence of associated conditions (e.g., autoimmunity, malignancy, infection, drugs, and paraproteinemia), a positive anti-phospholipase A2 receptor antibody test by ELISA and immunofluorescence assay confirms the diagnosis of membranous nephropathy noninvasively. These data have not been externally validated.
Design, Setting, Participants, & Measurements:
The clinical and pathologic characteristics of patients with a positive anti-phospholipase A2 receptor antibody test at the Mayo Clinic, the University Hospital Vall D'Hebron (Barcelona), and the Columbia University Medical Center (New York) were retrospectively reviewed. Biopsy findings and presence or absence of a potential associated condition were assessed.
Results:
From a total of 276 patients with positive anti-phospholipase A2 receptor serology, previously reported patients (n=33), kidney transplant recipients (n=9), pediatric patients (n=2), and patients without kidney biopsy (n=69) were excluded. Among the 163 remaining patients, associated conditions were identified in 47 patients, and 15 patients had diabetes mellitus. All 101 patients of the final cohort had a primary diagnosis of membranous nephropathy on kidney biopsy. In the 79 patients with eGFR≥60 ml/min per 1.73 m2, none of the biopsy findings altered diagnosis or management. Among the 22 patients with decreased eGFR, additional findings included superimposed acute interstitial nephritis (n=1).
Conclusions:
In patients with preserved eGFR and absence of associated conditions or diabetes, a positive anti-phospholipase A2 receptor test by either ELISA >20 RU/ml or a positive immunofluorescence assay confirms the diagnosis of membranous nephropathy, precluding the requirement for a kidney biopsy.
Insights
A positive anti-phospholipase A2 receptor antibody test can noninvasively diagnose membranous nephropathy in patients with normal kidney function and no other health conditions, eliminating the need for a kidney biopsy.
Area of Science:
- Nephrology
- Immunology
- Diagnostic Medicine
Background:
- Kidney biopsy is the gold standard for diagnosing membranous nephropathy.
- Anti-phospholipase A2 receptor (anti-PLA2R) antibodies are present in 70-80% of primary membranous nephropathy cases.
- Previous studies suggested noninvasive diagnosis via anti-PLA2R testing in specific patient groups, but external validation was lacking.
Purpose of the Study:
- To externally validate the noninvasive diagnosis of membranous nephropathy using anti-PLA2R antibody testing.
- To assess the diagnostic accuracy of anti-PLA2R serology in a multi-center cohort.
- To determine if kidney biopsy is necessary in patients with positive anti-PLA2R antibodies and preserved kidney function.
Main Methods:
- Retrospective review of clinical and pathological data from patients with positive anti-PLA2R antibody tests across three medical centers.
- Exclusion of patients with specific conditions (e.g., kidney transplant recipients, pediatric patients, those without biopsy).
- Assessment of biopsy findings and associated conditions in the final cohort.
Main Results:
- A final cohort of 101 patients with biopsy-confirmed membranous nephropathy was analyzed.
- In 79 patients with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m², biopsy findings did not alter diagnosis or management.
- Associated conditions were identified in 47 patients, and 15 had diabetes mellitus.
Conclusions:
- A positive anti-PLA2R antibody test (ELISA >20 RU/ml or positive immunofluorescence assay) confirms membranous nephropathy in patients with preserved eGFR and no associated conditions or diabetes.
- This noninvasive testing approach can preclude the need for kidney biopsy in eligible patients.
- External validation supports the use of anti-PLA2R serology for diagnosing membranous nephropathy.
