Cold ischemic injury of transplanted kidneys: new insights from experimental studies

Abstract

Kidney transplantation is the preferred and definitive treatment for end-stage renal disease (ESRD), and kidneys from deceased donors are a major source for it. These kidneys are routinely cold stored to prolong viability, which, however, when prolonged can cause injury, resulting in reduced graft function and survival. Recent experimental studies have identified the release of iron and free radicals, activation of calpain, and formation of F2-isoprostanes as important components of cold ischemic injury, as are the swelling of mitochondria and activation of mitochondrial apoptotic pathways. Moreover, studies have also suggested that fortifying the storage solution with deferoxamine or preconditioning the donor kidneys with hemeoxygenase-1 may prove viable clinical strategies to limit cold ischemic injury. This review will summarize these and other new experimental data that have implications for reducing cold ischemic transplant injury, a step necessary to improve deceased-donor allograft survival.

Cold Preservation Mediated Renal Injury: Involvement of Mitochondrial Oxidative Stress

“…[10,20] In a recent review by Salahudeen et al, it was stated that few (if any) studies had been designed to explore and compare the mechanism of reperfusion injury in cold preserved organs versus the more commonly studied warm I/R injury. [21] To measure the functional effect that cold preservation has on renal function, cold stored kidneys must be transplanted. For technical reasons related to transient immunosuppressive therapy (10 days) in our rat renal allograft transplant model, it is difficult to measure early (less than 24 hr) renal function of the transplanted organ.…”

Immediately Functioning Grafts from Brain-Dead Donors Treated with Extracorporeal Membrane Oxygenation

“…Its mechanisms of action may include protection against damage by oxygen free radicals 13 or reperfusion injury. 14 Alternatively, ECMO may reduce the severity of the subsequent innate immune response in the recipient, which stimulates the immunologic and inflam matory cascade and initiates a powerful response that can lead to graft rejection.…”

Cold Ischaemic Injury in Kidney Transplantation

“…This lowers the intracellular pH causing lysosomal instability and the activation of lytic enzymes [14,15]. The depletion of ATP also reduces a large number of cellular processes.…”

“…The binding of transition metals such as iron to their carrier proteins (transferrin, ferritin) is also inhibited which increases the intracellular concentration of free iron [16,17]. This is a strong catalyst for the generation of oxygen free radicals which promotes the production of other free radicals [14]. The impact of CI injury is evident immediately after transplantation when oxygenated blood is reintroduced into the kidney.…”