Remote ischemic preconditioning enhances renal function recovery after ischemia-reperfusion injury: potential role of lactate as a mediator

Remote ischemic preconditioning (RIPC) is a promising non-invasive approach to protect distant organs from ischemia reperfusion (IR) injury. However, the mediators involved in this process are not well understood. This study investigated the role of lactate as a potential mediator of RIPC-induced renoprotection in a rat model of renal IR injury. Male Sprague Dawley rats were assigned to four groups: Sham, IR (bilateral renal ischemia for 45 minutes followed by 24 h reperfusion), RIPC + IR (three cycles of 5-min hind limb ischemia/reperfusion before renal IR), and Lactate + IR (intraperitoneal sodium L-lactate before renal IR). Renal function was assessed by serum creatinine, blood urea nitrogen, and creatinine clearance. Renal histology was examined by light microscopy. Blood lactate levels were measured to confirm systemic effects of RIPC and lactate. IR caused significant renal injury, demonstrated by increased serum creatinine, BUN, and elevated histological damage. Both RIPC and lactate improved renal outcomes by lowering serum creatinine and BUN, and reducing tissue damage. RIPC and lactate also increased circulating lactate, supporting its role as a humoral mediator. RIPC protects against renal IR injury, potentially via increased circulating lactate. These findings highlight lactate as a promising target for interventions to mitigate renal IR injury.