Managing renal transplant ischemia reperfusion injury: novel therapies in the pipeline

Abstract

Ischemia reperfusion injury (IRI) is an early, non-specific inflammatory response that follows perfusion of warm blood into a cold asanguinous organ following transplantation. The occurrence of IRI may have a pivotal impact on acute and long-term renal allograft function. Initially, IRI contributes to delayed graft function (DGF), a term typically defined as the need for dialysis within one wk after renal transplantation. DGF frequently leads to prolonged hospital stay, increased healthcare costs, and potentially worse prognosis. Strategies to prevent IRI have so far been fairly limited, poorly defined, inadequately studied, and mostly anecdotal. The purpose of this review is to summarize the existing and novel therapies, which may mitigate IRI in renal transplantation. Agents currently in the pipeline include: Diannexin, which reduces endothelial cell injury by shielding phosphatidylserine; YSPSL, which mimics the binding portion of P-selectin glycoprotein ligand-1 to competitively inhibit translocation of P-selectin and recruitment of polymorphonuclear leukocytes to the surface of endothelial cells; and I5NP, a synthetic small interfering ribonucleic acid that results in the inhibition of p53 expression. These agents represent an exciting frontier in transplant pharmacotherapy; they are in various phases of investigation and may have broader benefits in reducing complications of DGF.