The classical triad of hemolytic uremic syndrome (microangiopathic hemolytic anemia, severe thrombopenia, and renal failure) developed de novo in three of our renal transplanted patients under cyclosporin A treatment. The predominant morphologic findings in the grafts consisted of glomerular and arteriolar thrombosis as well as arteriolonecrosis, all features of the syndrome. In one instance, ischemic bowel disease supervened after graft removal and was associated with persistent low grade microangiopathic process. De novo hemolytic uremic syndrome has been reported in patients treated with cyclosporin A following bone marrow or liver transplantation as well as in a few renal graft recipients. This peculiar form of cyclosporin A nephrotoxicity should not be confused with acute rejection of the renal transplant.
The combined effects of RAD and Neoral were tested in a rat orthotopic small-bowel transplantation model. Seven groups (n = 6) were involved in this study, and each one was included in three rejection models for the evaluation of host-vs.-graft disease (HVG) (LBN-F1 to LEW), graft-vs.-host disease (GVH) (LEW to LBN-F1), and combined HVG and GVH immune responses (BN to LEW). Both drugs were administered orally throughout the study. Low doses of RAD (1.0-2.5 mg/kg/day) combined with Neoral (2.0-5.0 mg/kg/day) produced strong synergistic effects in the prolongation of small-bowel graft survival in HVG (combination index, CI = 0.095, 0.1212), GVH (CI = 0.027, 0.020), and combined HVG and GVH immune responses (CI = 0.070, 0.301). The combination therapy of RAD and Neoral produces a strong synergistic effect toward the inhibition of HVG, GVH, and combined HVG and GVH immune responses in a rat small-bowel transplantation model.
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