Ischemia–reperfusion injury as the leading cause of primary non‐function in renal transplantation using donors with prolonged warm ischemic time

Renal transplantation (RTx) from marginal donors has been performed in most Japanese transplant centers because of severe donor organ shortage. RTx using marginal donors with prolonged warm ischemic time (WIT) has sometimes resulted in primary non-function (PNF). Among 53 cadaveric RTx performed at Kanazawa Medical University between October 1986 and May 2006, five cases using non-heart-beating donors resulted in PNF. In these five patients, histologic examination of one h RBx (graft biopsy one h after revascularization) revealed extensive congestion in glomerular and peritubular capillaries. Glomerular subendothelial swelling and mesangiolysis were also detected, and electron microscopic examination showed widening of the subendothelial spaces of glomerular capillaries. Such findings of endothelial damage were not detected in the other 48 cases without PNF. In contrast, no distinct abnormalities other than acute tubular necrosis were found in zero h RBx (graft biopsy before implantation) obtained from three patients with PNF. Prolonged WIT was the prominent feature of the five patients with PNF, and multiple logistic analysis showed that prolonged WIT was a significant risk factor for the development of endothelial damage on reperfusion. Paired allografts from the same donors of these five cases also ended in PNF. It is conceivable that the endothelial damage was caused by ischemia-reperfusion injury and extensive congestion followed as a result of endothelial injury. Ischemia-reperfusion injury is the leading cause of PNF in RTx using donors with prolonged WIT. Guidelines to assess the viability of marginal grafts should be established in the future to prevent transplantation of non-functioning grafts.