LONG-TERM FAILURE OF RENAL-TRANSPLANTS - ADDING INSULT TO INJURY

Long-term failure of renal transplants: Adding insult to injury. Altho ugh transplantation is the preferred choice for many end-stage renal d isease patients, results are far from perfect and the demand for organ s exceeds the available supply. After high initial success rates at on e year, the subsequent course of randomly HLA matched cadaveric organs is an exponential loss of functioning grafts, with a half-life of sev en to eight years. This process is one of progressive sclerosis and fi brosis which may result from the inability of available immunosuppress ive agents to control a chronic type of rejection, or it may be the re sult of early immunological injury with progressive vascular injury oc curring as a result of hemodynamically induced injuries, as seen in re nal ablation animal models. Matching for HLA antigens has a major impa ct on this process, with half-lives of 20 years with HLA-A, HLA-B, HLA -DR matched cadaver donors. Various clinical risk factors, including t he relative size of the donor kidney, ischemic injuries, and drug toxi cities all predispose to a more rapid rate of chronic graft loss. Thes e are likely to be additive to the damaging effects of rejection activ ity, with a final pathway of glomerulovascular sclerosis initiated whe n a critically low level of functioning nephrons is reached.