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Combined Serologic and Genetic Risk Score and Prognostication of Phospholipase A2 receptor-Associated Membranous Nephropathy
Clinical Journal of the American Society of Nephrology ( IF 9.8 ) Pub Date : 2024-02-29 , DOI: 10.2215/cjn.0000000000000422
Xiaofan Hu 1 , Jing Xu 1 , Wei Wang 2 , Lili Liu 3 , Yuanmeng Jing 1 , Chenni Gao 1 , Xialian Yu 1 , Yi Li 2 , Li Lin 1 , Jun Tong 1 , Qinjie Weng 1 , Xiaoxia Pan 1 , Wen Zhang 1 , Hong Ren 1 , Guisen Li 2 , Krzysztof Kiryluk 3 , Nan Chen 1 , Jingyuan Xie 1
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of 519 biopsy-proven PLA2R-associated primary membranous nephropathy patients with baseline eGFR ≥25 ml/min per 1.73 m2. The combined risk score was calculated by combining the genetic risk score with PLA2R ELISA antibody titers. The primary end point 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 with clinical factors alone, in predicting primary outcomes. Results The median age was 56 years (range, 15–82 years); the male-to-female ratio was 1:0.6, the median eGFR at biopsy was 99 ml/min per 1.73 m2 (range: 26–167 ml/min per 1.73 m2), and the median proteinuria was 5.3 g/24 hours (range: 1.5–25.8 g/24 hours). 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 tubulointerstitial lesions. The best-performing clinical model to predict kidney disease progression included age, eGFR, proteinuria, serum albumin, diabetes, and tubulointerstitial lesions (C-statistic 0.76 [0.69–0.82], adjusted R2 0.51). Although 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–serologic model=0.04 [0.01–0.06], P < 0.001). Conclusions In patients with PLA2R-associated membranous nephropathy, the combined risk score incorporating inherited risk alleles and PLA2R antibody enhanced the prediction of kidney disease progression compared with PLA2R serology and clinical factors alone....

中文翻译:

磷脂酶 A2 受体相关膜性肾病的血清学和遗传联合风险评分及预后

519 例活检证实的 PLA2R 相关原发性膜性肾病患者的基线 eGFR ≥25 ml/min 每 1.73 m2。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 每 1.73 m2(范围:26–167 ml/min 每 1.73 m2),中位蛋白尿为 5.3 g/24 小时(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,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,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。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)。尽管添加 PLA2R 抗体滴度改善了该模型的性能(C 统计量:0.78 [0.72–0.84],调整后的 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],调整后的 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肾脏疾病进展的预测。
更新日期:2024-02-29
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