Assessment of Preservation Induced Reperfusion Injury via Intraoperative Renal Transplant Blood Flow and Endothelin Concentration Studies

Abstract

Purpose We investigated a possible relationship between levels of the vasoconstrictive peptide endothelin and renal transplant reperfusion injury, and modified a technique for measuring renal blood flow with an ultrasonic perivascular transit time flow probe. Materials and Methods Renal grafts in a swine transplant model were cold flushed with either Collins-2 or University of Wisconsin solution. Renal blood flow and renal vein endothelin levels after reperfusion of transplanted grafts, as well as histological parameters within the transplanted kidney were measured. The 5-minute post-reperfusion renal blood flow was used as the baseline allograft flow. The definition of reperfusion injury was a decrease in flow from baseline with no recovery within 1 hour of reperfusion. In 9 human recipients reperfusion injury was further verified by monitoring subsequent serum creatinine, urine output, graft survival and rejection episodes. Results In the swine model and human transplant recipients no evidence of post-reperfusion ischemia was noted by histological examination, supporting that moderate to mild reperfusion injury or ischemic injury cannot be clinically determined with this method. In the swine model the decrease flow from baseline in allograft post-reperfusion renal blood flow was significantly greater in kidneys preserved in Collins'-2 than in University of Wisconsin solution (41.75 −/− 5.69 versus 11.18 −/− 13.99 ml. per minute, p = 0.005), supporting that this technique can assess mild to moderate reperfusion injury. The increase in serum endothelin in the allografts from the swine model and in humans was not significantly different from baseline. Clinically, post-reperfusion renal blood flow changes correlated well with subsequent function. The 4 patients with renal transplant reperfusion injury had significantly higher serum creatinine values and lower urine output 1 week postoperatively than 5 patients with no evidence of injury (serum creatinine: 6.75 −/− 3.03 versus 2.08 −/− 1.28 mg./dl., p = 0.015). Reperfusion injury patients had more rejections (2 versus 1) and less graft survival (75% versus 100%) at 1-year followup compared to the nonreperfusion injury patients. Conclusions Vasoactive factors other than endothelin most likely contribute to reperfusion injury. Furthermore, the ultrasonic transit time flow probe accurately measures post-reperfusion renal blood flow and offers a practical method for assessing acute reperfusion injury, which may help to optimize immunosuppressive strategies to decrease allograft loss associated with delayed graft function.