Severe acute renal failure after exposure to sirolimus-tacrolimus in two livin donor kidney reciplents

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Abstract
We began a clinical trial in African Americans comparing sirolimus-tacrolimus to standard immunosuppression. We report two African American male living donor kidney recipients who developed acute renal failure after exposure to sirolimus-tacrolimus. Both patients received similar doses of sirolimus and tacrolimus to achieve target levels of 5 to 15 ng/mL and prednisone in tapering doses. Renal function and tacrolimus and sirolimus levels were systematically monitored. Although both kidneys functioned immediately, acute oliguric renal failure developed approximately 2 weeks after transplantation. Transplant kidney biopsy showed acute tubular necrosis in patient 2. Sirolimus-tacrolimus was then stopped in both patients. Both patients required temporary hemodialysis. Renal function returned 2 weeks later and was normal 2 months after transplantation on tacrolimus plus mycophenolate mofetil. Combination sirolimus-tacrolimus may cause nephrotoxicity in some patients by mechanisms that are presently unexplained.