Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase

Clinical trials shows that remote ischemic preconditioning (IPC) can protect against contrast induced nephropathy (CIN) in risky patients, however, the exact mechanismis unclear. In this study, we explored whether renalase, an amine oxidase that has been previously shown to mediate reno-protection by local IPC, would also mediate the same effect elicited by remote IPC in animal model. Limb IPC was performed for 24 h followed by induction of CIN. Our results indicated that limb IPC prevented renal function decline, attenuated tubular damage and reduced oxidative stress and inflammation in the kidney. All those beneficial effects were abolished by silencing of renalase with siRNA. This suggests that similar to local IPC, renalase is also critically involved in limb IPC-elicited reno-protection. Mechanistic studies showed that limb IPC increased TNF alpha levels in the muscle and blood, and up-regulated renalase and phosphorylated I kappa B alpha expression in the kidney. Pretreatment with TNFa antagonist or NF-kappa B inhibitor, largely blocked renalase expression. Besides, TNFa preconditioning increased expression of renal renalase in vivo and in vitro, and attenuated H2O2 induced apoptosis in renal tubular cells. Collectively, our results suggest that limb IPC-induced reno-protection in CIN is dependent on increased renalase expression via activation of the TNF alpha/NF-kappa B pathway. (C) 2016 The Authors. Published by Elsevier B.V.