Remote Ischemic Preconditioning to Prevent Acute Kidney Injury After Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials

Abstract

Objective: Randomized controlled trials (RCTs) evaluating the influence of remote ischemic preconditioning (RIPC) on acute kidney injury (AKI) after cardiac surgery showed inconsistent results. We performed a meta-analysis to evaluate the efficacy of RIPC on AKI after cardiac surgery.Methods: Relevant studies were obtained by search of PubMed, Embase, and Cochrane's Library databases. A random-effect model was used to pool the results. Meta-regression and subgroup analyses were used to determine the source of heterogeneity.Results: Twenty-two RCTs with 5,389 patients who received cardiac surgery −2,702 patients in the RIPC group and 2,687 patients in the control group—were included. Moderate heterogeneity was detected (p for Cochrane's Q test = 0.03, I2 = 40%). Pooled results showed that RIPC significantly reduced the incidence of AKI compared with control [odds ratio (OR): 0.76, 95% confidence intervals (CI): 0.61–0.94, p = 0.01]. Results limited to on-pump surgery (OR: 0.78, 95% CI: 0.64–0.95, p = 0.01) or studies with acute RIPC (OR: 0.78, 95% CI: 0.63–0.97, p = 0.03) showed consistent results. Meta-regression and subgroup analyses indicated that study characteristics, including study design, country, age, gender, diabetic status, surgery type, use of propofol or volatile anesthetics, cross-clamp time, RIPC protocol, definition of AKI, and sample size did not significantly affect the outcome of AKI. Results of stratified analysis showed that RIPC significantly reduced the risk of mild-to-moderate AKI that did not require renal replacement therapy (RRT, OR: 0.76, 95% CI: 0.60–0.96, p = 0.02) but did not significantly reduce the risk of severe AKI that required RRT in patients after cardiac surgery (OR: 0.73, 95% CI: 0.50–1.07, p = 0.11).Conclusions: Current evidence supports RIPC as an effective strategy to prevent AKI after cardiac surgery, which seems to be mainly driven by the reduced mild-to-moderate AKI events that did not require RRT. Efforts are needed to determine the influences of patient characteristics, procedure, perioperative drugs, and RIPC protocol on the outcome.

Analysis of Risk Factors for Perioperative Acute Kidney Injury and Management Strategies

“…Zarbock et al (122) conducted a large, multicenter, randomized, double-blind clinical trial in 2015, which suggested that remote ischemic preadaptation significantly reduced the incidence of major adverse renal events at 90 days in patients undergoing high-risk cardiac surgery compared to controls, while suggesting that remote ischemic preadaptation may promote renal recovery in patients with perioperative AKI. Similarly, the results of two recent metaanalyses confirm this view (123,124). However, like others, this conclusion still faces contrary opinions.…”

Remote ischemic postconditioning protects against crush-induced acute kidney injury via down-regulation of apoptosis and senescence

“…It was shown that IPC ameliorated AKI induced by limb ischemia/reperfusion via inhibiting TLR4 and NF-κB signaling in rats [8]. A metaanalysis by Liu et al also supported the theory that remote ischemic preconditioning would effectively prevent AKI in patients after cardiac surgery [20]. However, the culminating events in the kidney after IPC are still ambiguous, especially in a crush syndrome model, which varies from typical ischemia-reperfusion injury models.…”

Remote ischemic conditioning improves rat brain antioxidant defense in a time-dependent mechanism

“…The different patterns observed in the muscle and in remote organs are possibly related to the underlying mechanisms of RIC. Longer cycles are necessary to activate different pathways supposed to be related to this technique and to evoke a protective effect in distant tissues, for instance, a neural pathway, in which sublethal ischemic stimulus provides an afferent signal to the central nervous system 16 , 20 , 21 . Consequently, there is an efferent response, through activation of parasympathetic nerves, that plays a role in modulating vascular activity and increasing anti-inflammatory substances 16 .…”