The effects of erythropoietin (EPO) and carbon monoxide (CO) on renal ischaemia/reperfusion (I/R) injury in an isolated porcine kidney model

Kidney transplantation remains the best modality for renal replacement therapy, the key problem being lack of suitable organs for transplantation. Thus renewed interest in non-heart-beating-donor (NHBD) organs is on the increase to bridge this gap. NHBD organs are subjected to ischaemia-reperfusion (I/R) injury; the underlying pathophysiology, a complex inter-related sequence leading to short and long term renal allograft dysfunction. The aim of the study was to validate normothermic resuscitation perfusion (NP) as a preservation model followed by investigating the use of erythropoietin (EPO) and carbon-monoxide (CO). Porcine kidneys were perfused with normothermic-autologus blood on an isolated-organ perfusion system (IOPS), design based on cardio-pulmonary bypass technology. Renal haemodynamics and functions were then measured during 3hr reperfusion. NP restored renal blood flow and improved renal function, as assessed by % serum creatinine fall, area under curve (AUC) of serum creatinine. EPO when added to NP did not seem to add any major benefit other than marginally improve oxygen consumption. Carbon monoxide delivered as carbon monoxide-releasing molecule-3 (CORM-3) was able to improve urine output, renal blood flow, reduce intrarenal resistance as well as improve renal function reflected by significant improvement in AUC of creatinine clearance. Normothermic resuscitation preservation not only reversed some of the deleterious effects of I/R injury, it also plays an important role as a versatile delivery system to assess various manipulatory agents that have potential in ameliorating I/R injury. This study provides further evidence that CO may be protective in renal perfusion injury and supports the use of low-dose CO releasing molecules as a method of CO delivery. Thus CORM-3 has the potential application in the field of NHBD kidney transplantation, which continues to be an expanding source of transplant kidneys. While EPO did not add any major benefits when used as a manipulating agent, may have its shortfall when applied to a NHBD kidney programme.