Introduction: The aim of this study was to test whether a combined risk score based on genetic risk and serology can improve the prediction of kidney failure in PLA2R-associated primary membranous nephropathy. Methods: We performed a retrospective analysis of 519 biopsy-proven PLA2R-associated primary membranous nephropathy patients with baseline eGFR ≥ 25ml/min/1.73m2. The combined risk score was calculated by combining the genetic risk score with PLA2R ELISA antibody titers. The primary endpoint was kidney disease progression defined as a 50% reduction in eGFR or kidney failure. Cox proportional hazard regression analysis and C-statistics were applied to compare the performance of PLA2R antibody, genetic risk score, and combined risk score, as compared to clinical factors alone, in predicting primary outcomes. Results: Median age was 56 years (range 15-82 years); male-to-female ratio was 1:0.6, median eGFR at biopsy was 99 ml/min/1.73m2 (range: 26-167 ml/min/1.73m2) and median proteinuria was 5.3 g/24h (range: 1.5-25.8 g/24h). During a median follow-up of 67 (5-200) months, 66 (13%) had kidney disease progression. In Cox proportional hazard regression models, PLA2R antibody titers, genetic risk score and combined risk score were all individually associated with kidney disease progression with and without adjustments for age, sex, proteinuria, eGFR and tubulo-interstitial lesions. The best-performing clinical model to predict kidney disease progression included age, eGFR, proteinuria, serum albumin, diabetes, and tubule-interstitial lesions [C-statistic 0.76 (0.69-0.82), adjusted R2 0.51]. While the addition of PLA2R antibody titer improved the performance of this model [C-statistic: 0.78 (0.72-0.84), adjusted R2 0.61], replacing PLA2R antibody with the combined risk score improved the model further [C-statistic: 0.82 (0.77-0.87), adjusted R2 0.69, difference of C-statistics with clinical model = 0.06 (0.03-0.10), P<0.001; difference of C-statistics with clinical-serological model = 0.04 (0.01-0.06), P<0.001 ]. Conclusion: In patients with PLA2R-associated membranous nephropathy, the combined risk score incorporating inherited risk alleles and PLA2R antibody enhanced prediction of kidney disease progression compared to PLA2R serology and clinical factors alone. Copyright © 2024 by the American Society of Nephrology

中文翻译：

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PLA2R 相关膜性肾病的血清学和遗传风险综合评分及预后

简介：本研究的目的是测试基于遗传风险和血清学的综合风险评分是否可以改善 PLA2R 相关原发性膜性肾病肾衰竭的预测。方法：我们对 519 例经活检证实的 PLA2R 相关原发性膜性肾病且基线 eGFR ≥ 25ml/min/1.73m2 的患者进行了回顾性分析。通过将遗传风险评分与 PLA2R ELISA 抗体滴度相结合来计算组合风险评分。主要终点是肾脏疾病进展，定义为 eGFR 降低 50% 或肾衰竭。应用 Cox 比例风险回归分析和 C 统计来比较 PLA2R 抗体、遗传风险评分和组合风险评分与单独的临床因素在预测主要结局方面的性能。结果：中位年龄为 56 岁（范围 15-82 岁）；男女比例为 1:0.6，活检时中位 eGFR 为 99 ml/min/1.73m2（范围：26-167 ml/min/1.73m2），中位蛋白尿为 5.3 g/24h（范围：1.5-25.8）克/24小时）。在中位随访 67 (5-200) 个月期间，66 名患者 (13%) 出现肾脏疾病进展。在 Cox 比例风险回归模型中，无论是否对年龄、性别、蛋白尿、eGFR 和肾小管间质病变进行调整，PLA2R 抗体滴度、遗传风险评分和综合风险评分均与肾脏疾病进展单独相关。预测肾脏疾病进展的最佳临床模型包括年龄、eGFR、蛋白尿、血清白蛋白、糖尿病和肾小管间质病变[C 统计量 0.76 (0.69-0.82)，调整后的 R2 0.51]。虽然添加 PLA2R 抗体滴度改善了该模型的性能 [C 统计量：0.78 (0.72-0.84)，调整 R2 0.61]，但用组合风险评分替换 PLA2R 抗体进一步改善了模型 [C 统计量：0.82 (0.77) -0.87），调整R2 0.69，C统计量与临床模型的差异= 0.06（0.03-0.10），P<0.001；C统计量与临床血清学模型的差异= 0.04（0.01-0.06），P<0.001]。结论：在 PLA2R 相关膜性肾病患者中，与单独的 PLA2R 血清学和临床因素相比，结合遗传风险等位基因和 PLA2R 抗体的综合风险评分增强了对肾脏疾病进展的预测。版权所有 © 2024 美国肾脏病学会