Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
PLoS One. 2012;7(2):e32296. doi: 10.1371/journal.pone.0032296. Epub 2012 Feb 28.
Ischemic preconditioning (IPC) is a potent renoprotective strategy which has not yet been translated successfully into clinical practice, in spite of promising results in animal studies. We performed a unique systematic review and meta-analysis of animal studies to identify factors modifying IPC efficacy in renal ischemia/reperfusion injury (IRI), in order to enhance the design of future (clinical) studies. An electronic literature search for animal studies on IPC in renal IRI yielded fifty-eight studies which met our inclusion criteria. We extracted data for serum creatinine, blood urea nitrogen and histological renal damage, as well as study quality indicators. Meta-analysis showed that IPC reduces serum creatinine (SMD 1.54 [95%CI 1.16, 1.93]), blood urea nitrogen (SMD 1.42 [95% CI 0.97, 1.87]) and histological renal damage (SMD 1.12 [95% CI 0.89, 1.35]) after IRI as compared to controls. Factors influencing IPC efficacy were the window of protection (<24 h = early vs. ≥ 24 h = late) and animal species (rat vs. mouse). No difference in efficacy between local and remote IPC was observed. In conclusion, our findings show that IPC effectively reduces renal damage after IRI, with higher efficacy in the late window of protection. However, there is a large gap in study data concerning the optimal window of protection, and IPC efficacy may differ per animal species. Moreover, current clinical trials on RIPC may not be optimally designed, and our findings identify a need for further standardization of animal experiments.
缺血预处理（IPC）是一种强大的肾保护策略，但尽管在动物研究中取得了有希望的结果，它尚未成功转化为临床实践。我们对动物研究进行了独特的系统评价和荟萃分析，以确定影响肾缺血/再灌注损伤（IRI）中 IPC 疗效的因素，以便增强未来（临床）研究的设计。对肾 IRI 中 IPC 的动物研究进行了电子文献检索，共获得了符合纳入标准的 58 项研究。我们提取了血清肌酐、血尿素氮和组织学肾损伤以及研究质量指标的数据。荟萃分析显示，IPC 可降低 IRI 后血清肌酐（SMD 1.54 [95%CI 1.16, 1.93]）、血尿素氮（SMD 1.42 [95%CI 0.97, 1.87]）和组织学肾损伤（SMD 1.12 [95%CI 0.89, 1.35]）与对照组相比。影响 IPC 疗效的因素是保护窗口（<24 h =早期与≥24 h =晚期）和动物物种（大鼠与小鼠）。局部 IPC 和远程 IPC 的疗效无差异。总之，我们的研究结果表明，IPC 可有效减轻 IRI 后的肾损伤，晚期保护窗口的疗效更高。然而，关于最佳保护窗口的研究数据存在较大差距，IPC 的疗效可能因动物物种而异。此外，目前关于 RIPC 的临床试验设计可能并不理想，我们的研究结果表明需要进一步规范动物实验。
