Investigation of renal ischaemia reperfusion injury using an isolated haemoperfused porcine kidney model

The aim of this study was to design and validate an isolated kidney haemoperfusion system while investigating the effects of three key factors influencing early graft injury and function; leucocyte activity, warm ischaemic time (WIT) and perfusion pressure.;Porcine kidneys were perfused with normothermic oxygenated autologous blood on an isolated organ perfusion system (IOPS) designed using cardiopulmonary bypass technology. Physiological and biochemical parameters were measured throughout the 6 hour perfusion period. Interval serum, urine and tissue samples were taken for physiological analysis, histological evaluation and assays measuring oxidative tissue injury, apoptosis and endovascular injury.;Kidneys perfused with leucocyte-depleted blood functioned significantly better than those perfused with whole blood in terms of creatinine clearance, oxygen consumption, acid-base homeostasis and renovascular haemodynamics. Haemoperfused kidneys demonstrated functional deterioration in parallel with increasing periods of warm ischaemia (7, 15, 25 and 40 minutes). Increasing WIT was also associated with elevated serum markers of oxidative protein and lipid injury and these correlated accurately with functional parameters. In contrast, elevated caspase 3 activity was associated with better renal function. A higher perfusion pressure of 95mmHg was associated with significantly improved renal function compared to sub-physiological pressures without increasing endovascular injury.;The IOPS represents a reliable and versatile model of IRI and as such has demonstrated that leucocyte depletion, WIT and perfusion pressure significantly affect early graft injury and function. The system offers extensive scope as a tool for evaluating IRI ameliorating interventions and in clinical organ viability assessment and preservation.