Abstract
Purpose
We sought to investigate the utility of anti-PLA2R antibody as a non-invasive screening method for the diagnosis of primary MN in patients with nephrotic syndrome (NS).
Methods
All consecutive patients with NS admitted in our department, between 01.01.2015 and 31.12.2019 were screened for anti-PLA2R antibodies by an ELISA assay (EUROIMMUN, Lübeck, DE). A positive anti-PLA2R serology was defined as an ELISA value over 2 RU/ml. Subsequently, all patients underwent kidney biopsy to confirm the histological diagnosis.
Results
Of the 203 patients with NS, we identified 67 patients with “high” titer of anti-PLA2R antibodies (> 20 RU/ml) and 47 patients with “intermediate” titer (2–20 RU/ml). In the entire cohort, the area under the curve (AUC) was 0.83 (95% CI 0.78–0.89; p < 0.001). With a cutoff of 20 RU/ml, the anti-PLA2R antibodies had a 64% sensitivity (95% CI 53–73%) and 94% specificity (95% CI 88–97%) to discriminate MN from other causes of NS. In addition, the PPV and NPV were 91% (95% CI 82–95%) and 75% (95% CI 69–79%). When analyzing the posttest effect, we identified a LR+ of 11.56 (95% CI 5.2–25.2) and LR− of 0.38 (95% CI 0.29–0.5). The overall accuracy of the test was 80.3% (95% CI 74–85%) and the diagnostic odds ratio was 30.42. When performing subgroup analysis, we identified that in younger patients, in those with preserved renal function or with negative workup for secondary causes, the diagnostic performance of anti-PLA2R antibodies was improved, the sensitivity increasing to 68–71%, the PPV to 93–95% and the LR+ to 12.23–15.4.
Conclusion
Serum anti-PLA2R antibody screening in patients with NS is a useful method for the diagnosis of primary MN. In younger patients (less than 60 years old) who have a preserved renal function and a negative workup for secondary causes of NS, a positive anti-PLA2R test highly predicts a diagnosis of primary MN.
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Data availability
The data presented in this study are available in the article “Anti-phospholipase A2 receptor antibody screening in nephrotic syndrome may identify a distinct subset of patients with primary membranous nephropathy”.
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Conceptualization: RJ, BO, GMir, and GI; data curation: RJ, BO, CA, GMic, BS, RB, AV, MG, CC, GS, LV, GMir, and GI; formal analysis: BO, BS, GS, GMir, and GI; investigation: RJ, BO, CA, GMic, BS, RB, AV, MG, CC, GS, LV, GMir, and GI; supervision: GMir and GI; writing—original draft: RJ, BO, GMir, and GI; writing—review and editing: RJ, BO, CA, GMic, BS, RB, AV, MG, CC, GS, LV, GMir, and GI. All the authors have read and agreed to the published version of the manuscript.
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The study was conducted with the provisions of the Declaration of Helsinki and the protocol was approved by the local ethics committee (The Ethics Council of Fundeni Clinical Institute, Registration number: 8851).
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Jurubiță, R., Obrișcă, B., Achim, C. et al. Anti-phospholipase A2 receptor antibody screening in nephrotic syndrome may identify a distinct subset of patients with primary membranous nephropathy. Int Urol Nephrol 54, 1713–1723 (2022). https://doi.org/10.1007/s11255-021-03061-9
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DOI: https://doi.org/10.1007/s11255-021-03061-9