Optimizing early de novo immunosuppression with sirolimus.

In the past, renal transplant deterioration was approached as a problem of "chronic rejection," which implied that deterioration of kidney function occurred because of past injuries that programmed the kidney for loss of function. New evidence suggests that deterioration occurs because of a new or recent source of injury. If a graft is losing function, the cause of deterioration needs to be identified. Some causes are treatable; those that are not should be diagnosed and further studied. To this end, we need to approach deterioration (loss of function or proteinuria) of renal transplant function by identifying distinct entities or components of the problem. Early and late kidney graft survival has improved considerably, owing to advances in clinical care, particularly immunosuppression. Many of the kidney transplants functioning today should serve their new owners for their life expectancy. The main cause of late kidney function deterioration remains allograft nephropathy. Often this reflects a failure of the immunosuppressive prescription. Subclinical rejection, chronic nephrotoxicity, recurrent disease, infections, or diabetes may contribute to this process. Optimal early and late immunosuppression is required to provide efficacy without attendant risk for graft dysfunction owing to nephrotoxicity. Because 1-year serum creatinine levels often provide an indication of long-term graft function, early evaluation of subtle degrees of graft dysfunction should prompt a graft biopsy to identify treatable causes.