南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (6): 1047-1050.doi: 10.12122/j.issn.1673-4254.2023.06.23

• • 上一篇    

药物基因检测在PLA2R相关性膜性肾病患者治疗中的效果

谭婷婷，郑义侯，李 芸，曾又佳   

  1. 深圳市中医院，广东 深圳 518000
  • 出版日期:2023-06-20 发布日期:2023-07-06

Pharmacogenetic testing improves treatment responses in patients with PLA2R-related membranous nephropathy

TAN Tingting, ZHENG Yihou, LI Yun, ZENG Youjia   

  1. Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518000, China
  • Online:2023-06-20 Published:2023-07-06

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摘要： 目的 本研究旨在探索药物基因检测对PLA2R相关性膜性肾病相关药物治疗的疗效及安全性的指导作用，以期为PLA2R相关性膜性肾病患者提供个体化精准药物治疗方案。方法 选取2019年1月~2021年10月在深圳市中医院肾病科住院的63例PLA2R相关性膜性肾病患者，其中33例为药物基因指导组，患者用药前均进行药物基因检测，通过筛选免疫抑制药物基因敏感性靶点给予免疫抑制药物，30例为对照组，患者按照指南经验性给予免疫抑制药物。回顾性分析两组人群免疫抑制药物的临床疗效及不良反应。比较两组患者性别、年龄、24 h尿蛋白定量、血清白蛋白、肾功能、血清抗磷脂酶A2受体抗体等，采用配对样本的t检验比较两组人群给药3月后，血清抗磷脂酶A2受体抗体、24 h尿蛋白定量、血清白蛋白、肾功能的差异；以及两组治疗前后的差异。结果 药物基因指导组33例患者中，环孢素表现为GG型的占51.5%，他克莫司表现为AG型的占61.6%，环磷酰胺表现为纯和缺失占51.5%、表现为AA型占63.6%。给药3月后血清抗磷脂酶A2受体抗体、24 h尿蛋白定量、血清白蛋白，药物基因指导组较对照组显著改善，差异有统计学意义（P<0.05）。结论 通过药物基因检测技术，个体化精准给予免疫抑制药物，有利于PLA2R相关性膜性肾病患者更精准地控制蛋白尿、血清抗磷脂酶A2受体抗体，提升血清白蛋白。

关键词: 药物基因组学；PLA2R相关性膜性肾病；个体化用药；免疫抑制药物

Abstract: Objective To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients. Methods A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment. Results Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (P<0.05). Conclusion Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.

Key words: pharmacogenomics; PLA2R-related membranous nephropathy; personalized medicine; immunosuppressive drugs