Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine. Sirolimus European Renal Transplant Study Group.

摘要: Background. Sirolimus (rapamycin) is a potent immunosuppressant with mechanism of action different from cyclosporine (CsA) or tacrolimus. Methods. In 11 European centers, first cadaveric renal allograft recipients were randomized to CsA (n=42) sirolimus (n=41). Dosing these agents was concentration-controlled and open-labeled. All patients received corticosteroids azathioprine. Results. At 12 months, graft survival (98% vs. 90% CsA), patient (100% 98%), incidence biopsy-confirmed acute rejection (41% 38%) similar. Serum creatinine lower sirolimus, significantly (P<0.05) so at 3 4 serum uric acid magnesium normal. Laboratory abnormalities reported more often included hypertriglyceridemia (51% 12%), hypercholesterolemia (44% 14%), thrombocytopenia (37% 0%), leukopenia (39% and, lesser importance, increased liver enzymes hypokalemia. These improved 2 months after transplantation when the target trough level lowered 30 15 ng/ml. Occurrence cytomegalovirus comparable (14% 12%); incidences herpes simplex (24% 10%, P=0.08) pneumonia (17% 2%, P=0.03) higher sirolimus. No gingival hyperplasia seen tremor rare, hypertension less frequent 33%). Two malignancies observed none Conclusions. Results suggest that can be used as base therapy in prophylaxis transplant rejection, has safety profile differs CsA.