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. 2021 Dec;16(12):1833-1839.
doi: 10.2215/CJN.05480421. Epub 2021 Nov 15.

Noninvasive Diagnosis of PLA2R-Associated Membranous Nephropathy: A Validation Study

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Noninvasive Diagnosis of PLA2R-Associated Membranous Nephropathy: A Validation Study

Shane A Bobart et al. Clin J Am Soc Nephrol. 2021 Dec.

Abstract

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.

Keywords: glomerulonephritis; kidney biopsy; membranous; membranous nephropathy; phospholipase A2; receptors.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Patients testing positive for anti-phospholipase A2 receptor (PLA2R) antibodies for three cohorts. NSAID, nonsteroidal anti-inflammatory drug.

Comment in

References

    1. Beck Jr., LH, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, Klein JB, Salant DJ: M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 361: 11–21, 2009 - PMC - PubMed
    1. Tomas NM, Beck Jr., LH, Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G, Dolla G, Hoxha E, Helmchen U, Dabert-Gay AS, Debayle D, Merchant M, Klein J, Salant DJ, Stahl RAK, Lambeau G: Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med 371: 2277–2287, 2014 - PMC - PubMed
    1. Sethi S, Debiec H, Madden B, Vivarelli M, Charlesworth MC, Ravindran A, Gross L, Ulinski T, Buob D, Tran CL, Emma F, Diomedi-Camassei F, Fervenza FC, Ronco P: Semaphorin 3B-associated membranous nephropathy is a distinct type of disease predominantly present in pediatric patients. Kidney Int 98: 1253–1264, 2020 - PubMed
    1. Sethi S, Debiec H, Madden B, Charlesworth MC, Morelle J, Gross L, Ravindran A, Buob D, Jadoul M, Fervenza FC, Ronco P: Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy. Kidney Int 97: 163–174, 2020 - PubMed
    1. Sethi S: New ‘antigens’ in membranous nephropathy. J Am Soc Nephrol 32: 268–278, 2021 - PMC - PubMed

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