[Kidney transplantation: how shall we deal with marginal cases? Future prospects from basic research]

Abstract

The research performed at the Department of Urology Osaka University Graduate School of Medicine is overviewed. Renal ischemia-reperfusion (I/R) injury is inevitable in transplantation and is related to longterm graft function. MF-1, a bifunctional hepatocyte growth factor-macrophage stimulating protein chimera, was found to prevent apoptosis. In our study, MF-1 directly guarded cultured proximal tubular epithelial cells from hypoxia-induced necrosis and apoptosis in vitro, and MF-1 treatment ameliorated renal dysfunction by preventing apoptosis in rat I/R injury model. The erythropoietin molecule modified by carbamylation (CEPO) has been identified and was demonstrated to protect several organs without increasing the hemoglobin concentration. The therapeutic effect of CEPO was evaluated using an endothelial tube formation assay, and a rat ischemia-reperfusion injury model. CEPO treatment induced more capillarylike formation than EPO. CEPO-treated kidneys showed minimal tubular apoptosis with increased peritubular capillary endothelial cells. We identified a new therapeutic approach using CEPO to protect the kidney from ischemia-reperfusion injury by promoting angiogenesis.