Chronic allograft nephropathy.

Despite dramatic declines in acute rejection and early graft failure, long-term outcomes after kidney transplantation have improved little during the past 25 years. Most late allograft failure is attributed to chronic allograft nephropathy, but this is a clinicopathological description and not a diagnosis, and its pathogenesis and treatment are largely unknown. Recent studies suggest that acute rejection during the first few months, and calcineurin inhibitor toxicity thereafter, may both contribute to chronic allograft nephropathy. There is also accumulating evidence that injury from antibody-mediated rejection may play an important pathogenic role in at least some patients with chronic allograft nephropathy, particularly those with transplant glomerulopathy. Therapeutic measures, including protocols to reduce calcineurin inhibitor exposure, remain largely unproven. Understanding why so many kidney allografts fail, despite effective preventive measures for early acute rejection, is one of the most important areas of research in kidney transplantation today.