Xia Tianyi, Zhu Sang, Wen Yan, Gao Shouhong, Li Mingming, Tao Xia, Zhang Feng, Chen Wansheng
Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Drug Des Devel Ther. 2018 Feb 28;12:417-428. doi: 10.2147/DDDT.S149340. eCollection 2018.
Nephrotoxicity of calcineurin inhibitors (CNIs) is the major concern for long-term allograft survival despite its predominant role in current immunosuppressive regime after renal transplantation. CNI nephrotoxicity is multifactorial with demographic, environmental, and pharmacogenetic flexibility, whereas studies indicating risk factors for CNI nephrotoxicity obtained incomplete or conflicting results.
A systematic review and meta-analysis of risk factors for CNI nephrotoxicity was performed on all retrieved studies through a comprehensive research of network database. Data were analyzed by Review Manager 5.2 with heterogeneity assessed using the Cochrane Q and tests. CNI nephrotoxicity was primarily indicated with protocol biopsy or index-based clinical diagnosis, and the secondary outcome was defined as delayed graft function.
Twelve observational studies containing a total of 2,849 cases were identified. Donor age (odds ratio [OR], 1.01; 95% CI, 1.01-1.03; =0.02), recipient zero-time arteriosclerosis (OR, 1.44; 95% CI, 1.04-1.99; =0.03), and genotype (OR, 2.80; 95% CI, 2.63-2.98; =0.00) were confirmed as risk factors for CNI nephrotoxicity. Subgroup and sensitivity analysis claimed donor age as a significant contributor in Asian and Caucasian areas.
Older donor age, recipient zero-time arteriosclerosis, and genotype might add up the risk for CNI nephrotoxicity, which could be interpreted into a robust biomarker system.
尽管钙调神经磷酸酶抑制剂（CNIs）在肾移植后的当前免疫抑制方案中起主要作用，但它对肾毒性的影响是长期同种异体移植存活的主要关注点。CNI肾毒性是多因素的，具有人口统计学、环境和药物遗传学方面的影响，而关于CNI肾毒性危险因素的研究结果并不完整或相互矛盾。
通过对网络数据库的全面检索，对所有检索到的关于CNI肾毒性危险因素的研究进行系统评价和荟萃分析。使用Review Manager 5.2对数据进行分析，并使用Cochrane Q检验和I²检验评估异质性。CNI肾毒性主要通过方案活检或基于指标的临床诊断来表明，次要结局定义为移植肾功能延迟。
共纳入12项观察性研究，总计2849例病例。供体年龄（比值比[OR]，1.01；95%置信区间[CI]，1.01 - 1.03；P = 0.02）、受体零时动脉粥样硬化（OR，1.44；95% CI，1.04 - 1.99；P = 0.03）和 基因型（OR，2.80；95% CI，2.63 - 2.98；P = 0.00）被确认为CNI肾毒性的危险因素。亚组和敏感性分析表明，供体年龄在亚洲和白种人地区是一个重要因素。
供体年龄较大、受体零时动脉粥样硬化和 基因型可能会增加CNI肾毒性的风险，这可以转化为一个强大的生物标志物系统。
