Clinical correlates to chronic renal allograft rejection

Chronic rejection is a clinical syndrome characterized by a progressive decline in renal allograft function and nonspecific histologic findings of interstitial fibrosis, glomerulosclerosis, and fibrointimal proliferation of intrarenal arteries. Most late allograft failure that is not due to death with a functioning allograft is caused by chronic rejection. Although the pathogenesis and treatment of chronic rejection are unknown, a number of epidemiological studies have examined clinical correlates for possible clues to its pathogenesis. Clinical correlates for chronic renal allograft rejection can be classified in two broad categories: immune (alloantigen-dependent) and non-immune (alloantigen-independent). The strongest evidence that chronic rejection is immune mediated comes from its association with acute rejection and the degree of histocompatibility mismatching. However, not all acute rejection leads to chronic rejection, and there is little evidence that newer immunosuppression regimens which effectively prevent acute rejection have reduced the incidence and severity of chronic rejection. Therefore, many clinical investigators have also looked for potential non-immune causes of chronic rejection. Putative non-immune risk factors include donor source (living-related vs. cadaveric), cold ischemia time, delayed graft function, size mismatching, donor age, donor and recipient gender, recipient race, hyperlipidemia, and hypertension. Although there is little evidence supporting a cause and effect relationship between any immune or non-immune risk factor and chronic rejection, these clinical associations suggest a number of potentially important areas for further study.