Ischemia Reperfusion Injury in Kidney Transplantation

Ischemia and reperfusion have been a natural step during kidney transplantation. Impairment of blood flow starts with brain death due to severe hemodynamic disturbances in cadaveric donor. Clamping of renal artery causes an absolute ischemia during harvesting operation. Cold ischemia during allograft kidney storage may also cause additional ischemic damages (Southard et al. 1985; Ploeg et al.1988; Dong & Tilney 2001). On the other hand, allograft kidney transplantation from living related donor is also subjected to warm ischemia beginning from arterial clamping. Following the blood flow reconstruction in kidney transplantation, the final stage of injury occurs during reperfusion –so called reperfusion injury. Ischemia reperfusion injury is actually an immediate nonspecific inflammatory response (Koo & Fuggle 2000). In this response, endothelium is activated by reactive oxygen species and inflammatory cytokines, then adhesion molecules like P-selectin and E-selectin are involved and induce the adherence of platelets to the epithelium. Leukocytes, initially neutrophils then monocytes and macrophages infiltrate into the affected tissue besides T lymphocytes (Koo & Fuggle 2002). The pathophysiological changes associated with ischemia/reperfusion injury in renal transplantation are not yet well defined although it has been studied extensively (Koo et al 1998). However, it is well known that prolonged cold ischemia is associated with delayed graft function with elevated creatinine levels in addition to inferior graft survival on long term follow up (Homer-Vanniasinkam et al.1997; Land 1999). Animal studies showed that the main mechanisms were related to leukocyte-endothelium interactions, reactive oxygen species, and the complement system (Kurokawa & Takagi 1999). Many interrelated pathways also control these fundamental biological systems. Free radicals appear to mediate tissue injury through lipid peroxidation and the activation of endothelial cells, resulting in functional and structural cell damage. Apoptosis and cell necrosis also take place as a result of injury. The disturbance of microcirculation in the graft besides mitochondria and some other cellular organelles are parts of these changes (Jassem et al. 2002). The main pathological changes are cellular death of affected tissue. Many other factors including the duration of ischemia dictate the magnitude of injury (Massberg et al. 1998; Land 1999; Gulec et al. 2006). The age and types of tissue are strongly correlated to the magnitude of damages in ischemia and reperfusion (Homer-Vanniasinkam et al.1997; Torras et al 1999).