Conversion from cyclosporine to tacrolimus in patients at risk for chronic renal allograft failure: 60-month results of the CRAF study

Background. This study compared the long-term effects of switching from cyclosporine to tacrolimus on the incidence, progression, and severity of chronic renal allograft failure in patients with elevated serum creatinine levels. Methods. Patients were assigned randomly (2:1) to switch to tacrolimus or remain on cyclosporine. Tacrolimus was initiated at 1/50th of the cyclosporine dose or 0.15 mg/kg/day, whichever dose was lower, to maintain trough concentrations between 5 and 15 ng/mL. Cyclosporine doses were adjusted to achieve trough concentrations between 100 and 300 ng/mL. Results. At 60 months, the median change from baseline in serum creatinine was -0.2 mg/dL in the tacrolimus group and 0.3 mg/dL in the cyclosporine group (P = 0.003). Median change in estimated creatinine clearance was 1.2 ml/min in the tacrolimus group and -4.1 mL/min in the cyclosporine group (P = 0.019). The incidence of new-onset diabetes, hyperglycemia, hypertension, lymphoma, and malignancies was generally low and comparable between groups. Fewer patients in the tacrolimus group than in the cyclosporine group developed new cardiac conditions (11% vs. 28%, P = 0.004), had low-density lipoprotein (LDL) cholesterol values more than 130 mg/dL (29% vs. 57%, P = 0.002), or developed hyperlipidemia (24% vs. 67%, P = 0.046) during the 60-month follow-up period. Despite these changes, patient and graft survival were similar for both groups. Conclusion. Switching from cyclosporine to tacrolimus resulted in improved renal function and a reduction in the occurrence of new-onset cardiac conditions and hyperlipidemia, with no increase in the incidence of new-onset diabetes or new-onset hyperglycermia. However, after 5 years there was no impact on patient or graft survival.