Abstract: We included 28 studies which randomised a total of 6851 patients. Risk of bias assessment indicated unclear to low risk of bias for most studies. For consistency regarding the direction of effects, continuous outcomes with negative values, and dichotomous outcomes with values less than one favour remote ischaemic preconditioning. Based on high quality evidence, remote ischaemic preconditioning made little or no difference to the reduction of serum creatinine levels at postoperative days one (14 studies, 1022 participants: MD -0.02 mg/dL, 95% CI -0.05 to 0.02; I2 = 21%), two (9 studies, 770 participants: MD -0.04 mg/dL, 95% CI -0.09 to 0.02; I2 = 31%), and three (6 studies, 417 participants: MD -0.05 mg/dL, 95% CI -0.19 to 0.10; I2 = 68%) compared to control. Serious adverse events occurred in four patients receiving remote ischaemic preconditioning by iliac clamping. It is uncertain whether remote ischaemic preconditioning by cuff inflation leads to increased adverse effects compared to control because the certainty of the evidence is low (15 studies, 3993 participants: RR 3.47, 95% CI 0.55 to 21.76; I2 = 0%); only two of 15 studies reported any adverse effects (6/1999 in the remote ischaemic preconditioning group and 1/1994 in the control group), the remaining 13 studies stated no adverse effects were observed in either group. Compared to control, remote ischaemic preconditioning made little or no difference to the need for dialysis (13 studies, 2417 participants: RR 0.85, 95% CI 0.37 to 1.94; I2 = 60%; moderate quality evidence), length of hospital stay (8 studies, 920 participants: MD 0.17 days, 95% CI -0.46 to 0.80; I2 = 49%, high quality evidence), or all-cause mortality (24 studies, 4931 participants: RR 0.86, 95% CI 0.54 to 1.37; I2 = 0%, high quality evidence). Remote ischaemic preconditioning may have slightly improved the incidence of acute kidney injury using either the AKIN (8 studies, 2364 participants: RR 0.76, 95% CI 0.57 to 1.00; I2 = 61%, high quality evidence) or RIFLE criteria (3 studies, 1586 participants: RR 0.91, 95% CI 0.75 to 1.12; I2 = 0%, moderate quality evidence). Remote ischaemic preconditioning by cuff inflation appears to be a safe method, and probably leads to little or no difference in serum creatinine, adverse effects, need for dialysis, length of hospital stay, death and in the incidence of acute kidney injury. Overall we had moderate-high certainty evidence however the available data does not confirm the efficacy of remote ischaemic preconditioning in reducing renal ischaemia reperfusion injury in patients undergoing major cardiac and vascular surgery in which renal ischaemia reperfusion injury may occur.

Plain-language summary: We performed a search off all available literature on 8 August 2016 to find all randomised controlled studies. 28 studies including 6851 patients were included in this analysis. Five studies included children undergoing cardiac surgery. Adult studies included patients undergoing major vascular surgery (three studies), cardiac surgery (nine studies), coronary bypass surgery (10 studies) and partial kidney resection (one study). The overall quality of the studies was acceptable. Twenty studies were funded without economical interest. One study was funded from a source with commercial interest. The other seven studies did not report funding. Remote ischaemic preconditioning performed with a blood pressure cuff appears to be safe as only two of 15 studies reported adverse effects (6/1999 in the remote ischaemic preconditioning group and 1/1994 in the control group). However remote ischaemic preconditioning by vascular clamping may cause vascular complications. Kidney injury in patients undergoing (surgical) procedures in which kidney injury may occur, was not reduced by remote Ischaemic preconditioning measured at day one, two or three after surgery. The need for dialysis, hospital stay and death were not reduced by remote ischaemic preconditioning. Although remote ischaemic preconditioning by cuff inflation is safe, available data do not confirm the efficacy of remote ischaemic preconditioning in reducing kidney injury.