Department of Nephrology, School of Medicine, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Nephrology, School of Medicine, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Clin J Am Soc Nephrol. 2024 May 1;19(5):573-582. doi: 10.2215/CJN.0000000000000422. Epub 2024 Feb 29.
The aim of this study was to test whether a combined risk score on the basis of genetic risk and serology can improve the prediction of kidney failure in phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy.
We performed a retrospective analysis of 519 biopsy-proven PLA2R-associated primary membranous nephropathy patients with baseline eGFR ≥25 ml/min per 1.73 m 2 . 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.
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 m 2 (range: 26-167 ml/min per 1.73 m 2 ), 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 R 2 0.51). Although the addition of PLA2R antibody titer improved the performance of this model (C-statistic: 0.78 [0.72-0.84], adjusted R 2 0.61), replacing PLA2R antibody with the combined risk score improved the model further (C-statistic: 0.82 [0.77-0.87], adjusted R 2 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).
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.
本研究旨在检验基于遗传风险和血清学的联合风险评分是否能提高磷脂酶 A2 受体（PLA2R）相关性原发性膜性肾病患者发生肾衰竭的预测能力。
我们对 519 例经活检证实的 PLA2R 相关性原发性膜性肾病患者进行了回顾性分析，这些患者的基线肾小球滤过率（eGFR）≥25ml/min/1.73m 2 。通过将遗传风险评分与 PLA2R ELISA 抗体滴度相结合，计算出联合风险评分。主要终点是定义为 eGFR 降低 50%或肾衰竭的肾脏疾病进展。应用 Cox 比例风险回归分析和 C 统计量比较 PLA2R 抗体、遗传风险评分和联合风险评分与临床因素单独预测主要结局的性能。
中位年龄为 56 岁（范围：15-82 岁）；男女比例为 1:0.6，活检时的中位 eGFR 为 99ml/min/1.73m 2 （范围：26-167ml/min/1.73m 2 ），中位蛋白尿为 5.3g/24 小时（范围：1.5-25.8g/24 小时）。在中位随访 67（5-200）个月期间，有 66 例（13%）发生了肾脏疾病进展。在 Cox 比例风险回归模型中，PLA2R 抗体滴度、遗传风险评分和联合风险评分在不调整年龄、性别、蛋白尿、eGFR 和肾小管间质病变的情况下，均与肾脏疾病进展相关。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 R 2 0.51）。虽然 PLA2R 抗体滴度的加入提高了该模型的性能（C 统计量：0.78[0.72-0.84]，调整后 R 2 0.61），但用联合风险评分代替 PLA2R 抗体进一步改善了该模型（C 统计量：0.82[0.77-0.87]，调整后 R 2 0.69，与临床模型相比的 C 统计量差异=0.06[0.03-0.10]，P<0.001；与临床-血清学模型相比的 C 统计量差异=0.04[0.01-0.06]，P<0.001）。
在 PLA2R 相关性膜性肾病患者中，纳入遗传风险等位基因和 PLA2R 抗体的联合风险评分提高了对肾脏疾病进展的预测能力，优于 PLA2R 血清学和临床因素单独预测。
