Preconditioning Strategies for Kidney Ischemia Reperfusion Injury: Implications of the “Time-Window” in Remote Ischemic Preconditioning

Remote ischemic preconditioning (IP) is a potential renoprotective strategy. However, there has been no demonstrated result in large animals and the role of time window in remote IP remains to be defined. Using a single-kidney porcine model, we evaluated organ protective function of remote IP in renal ischemia reperfusion injury. Fifteen Yorkshire pigs, 20 weeks old and weighing 35–38 kg were used. One week after left nephrectomy, we performed remote IP (clamping right external iliac artery, 2 cycles of 10 minutes) and right renal artery clamping (warm ischemia; 90 minutes). The animals were randomly divided into three groups: control group, warm ischemia without IP; group 1 (remote IP with early window [IP-E]), IP followed by warm ischemia with a 10-minute time window; and group 2 (remote IP with late window [IP-L]), IP followed by warm ischemia after a 24-hour time window. There were no differences in serum creatinine changes between groups. The IP-L group had lower urinary neutrophil gelatinase-associated lipocalin than control and IP-E at 72 hours post-ischemia. At 72 hours post-ischemia, the urinary kidney injury molecule-1 (KIM-1) was lower in the IP-L group than in the control and IP-E groups, and the IP-L group KIM-1 was near pre-ischemic levels, whereas the control and IP-E group KIM-1 levels were rising. Microalbumin also tended to be lower in the IP-L group. Taken together, remote IP showed a significant reduction in renal injury biomarkers from ischemia reperfusion injury. To effectively provide kidney protection, remote IP might require a considerable, rather than short, time window of ischemia.