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中华肾病研究电子杂志 ›› 2026, Vol. 15 ›› Issue (01) : 34 -38. doi: 10.3877/cma.j.issn.2095-3216.2026.01.006

综述

APOL1相关肾病:从遗传机制到靶向治疗的新进展
何智尧, 陈佳(), 陈客宏()   
  1. 400042 重庆,陆军特色医学中心肾脏内科、重庆市肾脏疾病精准诊治重点实验室
  • 收稿日期:2025-02-13 出版日期:2026-02-28
  • 通信作者: 陈佳, 陈客宏
  • 基金资助:
    国家自然科学基金(82270768); 重庆市科技创新引导课题-院士专项(2022YSZX-JCX0007CSTB); 重庆市自然科学基金(CSTB2023NSCQ-MSX0584)

APOL1-associated kidney disease: recent advances from genetic mechanisms to targeted therapy

Zhiyao He, Jia Chen(), Kehong Chen()   

  1. Department of Nephrology, Army Medical Center of Chinese PLA, Chongqing Key Laboratory of Precision Diagnosis and Treatment for Kidney Diseases, Chongqing 400042, China
  • Received:2025-02-13 Published:2026-02-28
  • Corresponding author: Jia Chen, Kehong Chen
引用本文:

何智尧, 陈佳, 陈客宏. APOL1相关肾病:从遗传机制到靶向治疗的新进展[J/OL]. 中华肾病研究电子杂志, 2026, 15(01): 34-38.

Zhiyao He, Jia Chen, Kehong Chen. APOL1-associated kidney disease: recent advances from genetic mechanisms to targeted therapy[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2026, 15(01): 34-38.

APOL1相关肾病是一种由载脂蛋白L1(apolipoprotein L1,APOL1)风险变异介导的肾脏疾病,主要表现为局灶节段性肾小球硬化。目前尚无特效疗法,现有非特异性治疗方案疗效有限。随着对APOL1 G1/G2风险变异及新近报道的p.T272I变异致病机制研究的深入,靶向APOL1的治疗药物(如小分子抑制剂、反义寡核苷酸、Janus激酶抑制剂)已陆续进入临床研究阶段。本文综述了近年来APOL1相关肾病从遗传机制到靶向治疗的最新进展。

Apolipoprotein L1-associated kidney disease is a renal disorder mediated by risk variants in the apolipoprotein L1 (APOL1) gene, predominantly manifesting as focal segmental glomerulosclerosis (FSGS). Currently, there is no specific therapy, and the efficacy of existing non-specific treatment regimens remains suboptimal. With the deepening understanding of the pathogenic mechanisms underlying APOL1 G1/G2 risk variants and the recently reported p. T272I variant, targeted therapeutic agents, such as small-molecule inhibitors, antisense oligonucleotides, and Janus kinase inhibitors, have successively entered clinical investigation. This article reviews the latest advances in APOL1-associated kidney disease, spanning from genetic mechanisms to targeted therapeutics.

图1 APOL1相关肾病发病机制注:IFN:interferon,干扰素;TNF:tumor necrosis factor,肿瘤坏死因子;TLR3:Toll-like receptor 3, Toll样受体3;Caspase-1:半胱氨酸天冬氨酸蛋白酶1;IL-1β:interleukin-1β,白细胞介素-1β;miR-193a:微小RNA-193a;SuPAR:可溶性尿激酶型纤溶酶原激活物受体
图2 APOL1基因检测结果阳性的分析与管理流程图
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