In vitro and in vivo models of renal ischemia reperfusion injury

Successful kidney transplantation is a life-saving procedure to patients with irreversible chronic renal failure. Despite the presence of various obstacles facing this surgery, preserving donor kidney and consequent ischemia reperfusion injury (IRI) are still major challenges affecting renal function as well as prognosis of transplant surgery. This study pursued two main aims: firstly, characterising changes in damage associated inflammatory gene expressions through developing, and analysis of an in vitro model of proximal tubular epithelial cells (PTEC) of normal human kidney mimicking renal IRI in vivo. The second aim was to simulate the concurrence of factors relevant to human intervention (renoprotective anaesthesia, peri- and postoperative analgesia, volume substitution) in mice deficient of properdin and congenic controls and to allow long-term observation of renal outcome after IRI. In this study, a reproducible and standardisable in vitro model was developed. It demonstrated the complexity of signalling where a multitude of factors affects the target cells. Secondly, the use of congenic properdin deficient mice showed that properdin has a significant role to play in renal injury (and recovery). There was significant impairment in renal function (and structure) compared to wildtype mice after IRI.