Long-term failure of renal transplants: adding insult to injury

Although transplantation is the preferred choice for many end-stage renal disease patients, results are far from perfect and the demand for organs exceeds the available supply. After high initial success rates at one year, the subsequent course of randomly HLA matched cadaveric organs is an exponential loss of functioning grafts, with a half-life of seven to eight years. This process is one of progressive sclerosis and fibrosis which may result from the inability of available immunosuppressive agents to control a chronic type of rejection, or it may be the result of early immunological injury with progressive vascular injury occurring as a result of hemodynamically induced injuries, as seen in renal ablation animal models. Matching for HLA antigens has a major impact on this process, with half-lives of 20 years with HLA-A, HLA-B, HLA-DR matched cadaver donors. Various clinical risk factors, including the relative size of the donor kidney, ischemic injuries, and drug toxicities all predispose to a more rapid rate of chronic graft loss. These are likely to be additive to the damaging effects of rejection activity, with a final pathway of glomerulovascular sclerosis initiated when a critically low level of functioning nephrons is reached.