血清补体4与原发性膜性肾病复发的关联：一项多中心回顾性队列研究

The association between serum complement 4 and relapse of primary membranous nephropathy: a multicenter retrospective cohort study.

作者信息

Gan Wenyuan, Zhu Fan, Zeng Xingruo, Xiao Wei, Fang Xun, Su Licong, Chen Wenli

机构信息

Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China.

出版信息

Front Med (Lausanne). 2024 Nov 11;11:1451677. doi: 10.3389/fmed.2024.1451677. eCollection 2024.

DOI:10.3389/fmed.2024.1451677

PMID:39588186

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11586214/

Abstract

BACKGROUND

Relapse after initial remission reduces renal survival in patients with primary membranous nephropathy (PMN). In this study, we aim to identify risk factors of relapse in PMN and construct a model to identify patients at high risk of relapse early.

METHODS

We conducted a multi-center retrospective study using the China Renal Data System database, which includes data from 24 urban academic centers across China. A prediction model based on the Cox proportional hazards model was derived in the derivation group and validated in the validation group.

RESULT

515 patients with biopsy-proven PMN achieving initial remission were enrolled. 32.62% of patients subsequently relapsed during a median of 6.08 months. Lower serum albumin (Alb) (per 1 g/L decrease, hazard ratio [HR] =1.48, 95% confidence interval [CI] 1.29-1.78, < 0.001), lower estimated glomerular filtration rate (eGFR) (per 10 mL/min/1.73m decrease, HR =1.14, 95% CI 0.97-1.49, < 0.001), higher serum complement 4 (C4) (per 0.1 g/L increase, HR =1.89, 95% CI 1.32-3.22, = 0.012), partial remission (PR) (HR =2.28, 95%CI 1.74-4.04, < 0.001), and treatment with calcineurin inhibitors (CINs) (HR =1.33, 95%CI 1.04-1.64, < 0.001) at the time of remission were risk factors for relapse. C-statistic, time-dependent areas under the receiver operating characteristic curve, and calibration plots confirmed that the model had excellent discrimination and calibration in predicting PMN relapse. The anti-phospholipase A2 receptor antibody (aPLA2Rab) titers and pathologic features did not substantially improve the model.

CONCLUSION

Our study confirms the well-known low Alb and eGFR, PR, and treatment of CNIs at the time of remission as risk factors for PMN relapse, but aPLA2Rab and pathologic features may not predict relapse. In addition, it is the first study to show serum C4 is associated with PMN relapse. We suggest that complement-targeted therapies may be a potential therapy to prevent PMN relapse.

摘要

背景

原发性膜性肾病（PMN）患者初次缓解后复发会降低肾脏存活率。在本研究中，我们旨在确定PMN复发的危险因素，并构建一个模型以早期识别复发高危患者。

方法

我们使用中国肾脏数据系统数据库进行了一项多中心回顾性研究，该数据库包含来自中国24个城市学术中心的数据。在推导组中基于Cox比例风险模型推导预测模型，并在验证组中进行验证。

结果

纳入515例经活检证实为PMN且初次缓解的患者。32.62%的患者随后在中位6.08个月内复发。缓解时血清白蛋白（Alb）水平较低（每降低1 g/L，风险比[HR]=1.48，95%置信区间[CI] 1.29-1.78，P<0.001）、估算肾小球滤过率（eGFR）较低（每降低10 mL/min/1.73m²，HR =1.14，95% CI 0.97-1.49，P<0.001）、血清补体4（C4）水平较高（每升高0.1 g/L，HR =1.89，95% CI 1.32-3.22，P =0.012）、部分缓解（PR）（HR =2.28，95%CI 1.74-4.04，P<0.001）以及缓解时使用钙调神经磷酸酶抑制剂（CINs）治疗（HR =1.33，95%CI 1.04-1.64，P<0.001）是复发的危险因素。C统计量、受试者工作特征曲线下的时间依赖性面积以及校准图证实该模型在预测PMN复发方面具有出色的辨别力和校准能力。抗磷脂酶A2受体抗体（aPLA2Rab）滴度和病理特征并未显著改善该模型。