Calcineurin-based immunosuppression in renal transplantation : focus on efficacy, the role of steroids, and the cardiovascular risk

Tacrolimus has proven to be superior to cyclosporin-Sandimmune with regard to the prevention of acute rejections, but data comparing tacrolimus with Neoral are scarce. Studied were 128 consecutive renal transplant recipients. They were treated with Neoral-based (n=74) or tacrolimus-based (n=54) immunosuppressive regimens. Survival analyses (Cox regression analysis) were performed on an intention-totreat basis. Renal function and cardiovascular risk profile were analyzed with a repeated measures ANOVA up to 12 months post-transplantation. Immunological features were less favourable in the tacrolimus group. Two-year patient and graft survival were comparable. Acute rejection-free survival was 82% in the tacrolimus group versus 40% in the Neoral group (P<0.0001). The severity of the rejections (1997 Banff classification) was comparable (P=0.43). Immunological graft loss (3.7% versus 12.2%, P=0.02) and conversion because of rejection (0% versus 28.4%, P<0.001) were less in the tacrolimus group. A higher proportion (68.5% versus 14.9%, P<0.001) was successfully put on monotherapy. Creatinine clearance, proteinuria, and fractional uric acid clearance were similar. In the tacrolimus group mean blood pressure was comparable, but patients needed less anti-hypertensive drugs (P<0.001) and, even with fewer patients on lipidlowering drugs, total cholesterol was lower (5.2 versus 6.0 mmol/l, P=0.003). Treatment for post-transplant diabetes mellitus was 18.5% versus 10.8% (P=0.22). In both groups, most patients could be withdrawn from anti-diabetic medication. This study indicates that tacrolimus is superior to cyclosporin-Neoral in preventing acute rejection with comparable patient and graft survival rates. Because of a lower need for treatment of hypertension and hypercholesterolemia, the cardiovascular risk profile is more favourable. A considerable proportion of patients can be successfully weaned from co-medication and treated with tacrolimus monotherapy.