Noninvasive Diagnosis of PLA2R-Associated Membranous Nephropathy

Abstract

Background and objectivesKidney 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, & measurementsThe 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.ResultsFrom 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).ConclusionsIn 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.

Challenges in Diagnosis and Management of Glomerular Disease in Resource-Limited Settings

“…Study of kidney tissue needs to be supplemented with other tests, such as serology and genetic testing. In some cases, these tests can obviate the need for a biopsy (16). For example, according to the latest KDIGO Guidelines a kidney biopsy is not required to confirm the diagnosis of membranous nephropathy in patients with nephrotic syndrome and a positive anti-PLA2R antibody test (7).…”

“…In some cases, these tests can obviate the need for a biopsy. 16 For example, according to the latest Kidney Disease Improving Global Outcomes Guidelines a kidney biopsy is not required to confirm the diagnosis of membranous nephropathy in patients with nephrotic syndrome and a positive antiphospholipase A2 receptor antibody test. 7 The survey identified major limitations to access these tests.…”

A case of Gitelman syndrome with membranous nephropathy

“…PLA2R-associated MN is an auto-immune disease, characterized by non-inflammation mediated subepithelial immune complex deposition with diffuse thickening of glomerular basement membrane. Approximately 70-80% of patients with primary MN have circulating PLA2R antibodies [ 22 ]. Renal pathology of this patient we described was MN, with increased titer of serum PLA2R antibody.…”

Incidence of Glomerulonephritis after SARS-CoV-2 mRNA Vaccination

“…We calculated incidence rate ratios for the total of all four glomerulonephritides and for each diagnosis separately by dividing the observed cases in 2021 by the expected cases and expressed uncertainty using 95% credible intervals. Because the availability of serologic testing for anti-PLA2R autoantibodies may have influenced biopsy practice over time, 16 we performed a sensitivity analysis excluding MN.…”