Prevention of Ischemia-Reperfusion Injury in Human Kidney Transplantation: A Meta-Analysis of Randomized Controlled Trials

Context: Using the marginal and expanded criteria organs increases the risk of ischemia-reperfusion injury (IRI), which remains unavoidable concerning issue after kidney transplantation (KT). While numerous trials have tested novel pharmaceutical approaches on animal models, little attempt has been made to assess the reproducibility of those results in the human setting. This study aimed to conduct a systematic review and meta-analysis to identify and abstract existing prophylactic strategies performed to reduce the risk of IRI after KT in human clinical trials. Evidence Acquisition: A comprehensive search was performed in MEDLINE, EMBASE, and Science Citation Index Expanded to detect relevant clinical trials until January 1, 2019. Two independent reviewers assessed the study eligibility, abstracted data, and evaluated the risk of bias. The prevention strategies in the included studies were categorized by one urologist. The fixed or random-effects model was selected based on the level of heterogeneity between studies in each category. The Cochran Q-test and I2 statistics were used to quantify the level of heterogeneity. The risk ratio (RR) of the delayed graft function (DGF) was calculated as the summary effect size of the primary outcome. Results: A total of 33 randomized controlled trials (31,334 patients) were categorized into seven groups based on the preventive hypotheses. Significant effects on DGF were observed in favor of the machine perfusion organ storage (RR = 0.73; 95% CI = 0.7 to 0.76; I2 = 0%) and use of antioxidant agents (RR = 0.6; 95% C = 0.46 to 0.78; I2 = 33%). There were no significant effects by innate inhibitors (RR = 0.86; 95% CI = 0.6 to 1.23; I2 = 58%), anti-inflammatory agents (RR = 0.86; 95% CI = 0.62 to 1.19; I2 = 0%), calcium-channel blockers (CCBs) (RR = 0.67; 95% CI = 0.3 to 1.49; I2 = 76%), conditioning (RR = 0.83; 95% CI = 0.59 to 1.16; I2 = 16%), and donor management techniques (RR = 0.88; 95% CI = 0.64 to 1.2; I2 = 57%). Conclusions: This review supports the use of machine perfusion organ storage and administration of antioxidant agents. However, the clinical application of innate inhibitors, anti-inflammatories, CCBs, conditioning, and donor management techniques needs further investigations in large scales (PROSPERO number: CRD42019132985).