Ex vivo use of a Rho-kinase inhibitor during renal preservation improves graft function upon reperfusion

BackgroundActivation of the Rho–Rho-kinase pathway has been shown to cause vasoconstriction in renal afferent arterioles. Vascular dysfunction plays a pivotal role in triggering reperfusion injury after kidney transplantation. Therefore, the effect of a Rho-kinase inhibitor, added to the preservation solution, on renal function after 18 h of storage at 4 °C was evaluated.MethodsPorcine kidneys were preserved with cold HTK-solution. During preservation, in the study group, HTK was supplemented with the Rho-kinase inhibitor HA1077, whereas the control group received no further treatment (n = 6, respectively). Kidney function after 18 h of storage at 4 °C was evaluated by 90 min of isolated reperfusion in vitro.ResultsRho-kinase inhibition (RKI) was associated with significantly higher renal perfusate flow compared to the control group. Endothelial function, as measured by perfusate levels of nitric oxide and gene expression of eNOS, was significantly increased in the study group. In our model, RKI also significantly improved glomerular function (clearance of creatinine) as well as tubular cell integrity as reflected by reduced fractional sodium excretion and release of fatty acid binding protein, a specific tubular cell marker.ConclusionOur results indicate that blocking the Rho-kinase pathway during cold preservation may lead to a better graft function upon reperfusion.