Ragy Omar, Abass Wessam, Kanigicherla Durga Anil K, Shinkins Bethany, Bestall Janine, King Natalie, Brenchley Paul, Smith Alison, Hamilton Patrick
Manchester Institute of Nephrology and Transplantation, Manchester University NHS Foundation Trust, Manchester, UK.
Division of Cardiovascular Sciences, University of Manchester, Manchester, UK.
Nephrol Dial Transplant. 2025 Aug 1;40(8):1458-1469. doi: 10.1093/ndt/gfaf012.
The phospholipase A2 receptor antibody (PLA2R-Ab) test is a valuable first-line diagnostic tool for primary membranous nephropathy (MN), helping to identify PLA2R-related MN and potentially eliminating the need for a kidney biopsy in some individuals. By reducing the reliance on biopsies, the test streamlines diagnosis and improves patient care. However, determining the optimal PLA2R measurement method and cut-off is critical to maximizing the benefits of the test and minimizing any harms. A systematic review and meta-analysis were performed to evaluate serum- and urine-based biomarkers for distinguishing between PLA2R-related MN and non-PLA2R MN. Searches were conducted in databases including Medline, Embase, Cochrane Library, Scopus, Web of Science, International HTA Database and ClinicalTrials.gov. The methodology followed Cochrane-recommended guidelines for systematic reviews and meta-analyses, and the QUADAS-2 tool was utilized to assess the overall risk of bias. Ninety-one studies met the eligibility criteria for inclusion in the review. Of these, 38 studies reporting the accuracy of the PLA2R-Ab test using the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) method and 27 using the EUROIMMUN immunofluorescence (IF) method were suitable for meta-analysis. The pooled sensitivity and specificity of EUROIMMUN ELISA at a cut-off value of 20 RU/mL were 0.64 [95% confidence interval (CI) 0.56-0.72] and 94.7% (95% CI 90.5-97.1%), respectively. The pooled sensitivity and specificity of EUROIMMUN IF at a threshold of 1:10 was 0.69 (95% CI 0.637-0.739) and 0.98 (95% CI 0.931-0.994), respectively. Risk of bias was higher for studies evaluating the IF compared with ELISA test. We also explored whether the timing of the index test had an impact on the pooled diagnostic accuracy results; no significant differences were found. By evaluating the specificity and sensitivity of EUROIMMUN ELISA PLA2R-Ab and IF, we demonstrate that at ELISA levels ≥20 RU/mL, alongside thorough secondary screening, a kidney biopsy may be unnecessary. However, lower or negative levels still warrant a biopsy.
磷脂酶A2受体抗体（PLA2R-Ab）检测是原发性膜性肾病（MN）的一项重要一线诊断工具，有助于识别与PLA2R相关的MN，并可能使一些患者无需进行肾活检。通过减少对活检的依赖，该检测简化了诊断过程并改善了患者护理。然而，确定最佳的PLA2R测量方法和临界值对于最大化检测益处并最小化任何危害至关重要。进行了一项系统评价和荟萃分析，以评估用于区分与PLA2R相关的MN和非PLA2R MN的基于血清和尿液的生物标志物。在包括Medline、Embase、Cochrane图书馆、Scopus、Web of Science、国际卫生技术评估数据库和ClinicalTrials.gov在内的数据库中进行了检索。该方法遵循Cochrane推荐的系统评价和荟萃分析指南，并使用QUADAS-2工具评估总体偏倚风险。91项研究符合纳入该评价的资格标准。其中，38项报告使用EUROIMMUN酶联免疫吸附测定（ELISA）方法检测PLA2R-Ab准确性的研究和27项使用EUROIMMUN免疫荧光（IF）方法的研究适合进行荟萃分析。EUROIMMUN ELISA在临界值为20 RU/mL时的合并敏感性和特异性分别为0.64[95%置信区间（CI）0.56-0.72]和94.7%（95%CI 90.5-97.1%）。EUROIMMUN IF在阈值为1:10时的合并敏感性和特异性分别为0.69（95%CI 0.637-0.739）和0.98（95%CI 0.931-0.994）。与ELISA检测相比，评估IF的研究偏倚风险更高。我们还探讨了索引检测的时间是否对合并诊断准确性结果有影响；未发现显著差异。通过评估EUROIMMUN ELISA PLA2R-Ab和IF的特异性和敏感性，我们证明在ELISA水平≥20 RU/mL时，除了进行全面的二次筛查外，可能无需进行肾活检。然而，较低或阴性水平仍需要进行活检。
