Hamdy AF et al. (2005) Comparison of sirolimus with low-dose tacrolimus versus sirolimus-based calcineurin inhibitor-free regimen in live donor renal transplantation. Am J Transplant 5: 2531–2538

Watson CJE et al. (2005) A randomized controlled trial of late conversion from CNI-based to sirolimus-based immunosuppression following renal transplantation. Am J Transplant 5: 2496–2503

Calcineurin inhibitors (CNIs) such as ciclosporin and tacrolimus are nephrotoxic, and contribute to late dysfunction of renal grafts. New results from two randomized controlled trials, published in the American Journal of Transplantation, support a CNI-free maintenance immunosuppression regimen based on the less-toxic drug sirolimus.

In a study of 132 live-donor kidney transplant recipients randomized 1:1 to either sirolimus plus low-dose tacrolimus or sirolimus plus mycophenolate mofetil, Hamdy et al. found rates of patient and graft survival to be similar. There was a trend towards less-frequent acute rejection in the CNI-free group. Renal function—measured by serum creatinine and glomerular filtration rate (GFR)—was superior in the CNI-free group after 24 months of follow-up (P = 0.017 for serum creatinine and P = 0.005 for GFR). This finding was repeated in a trial by Watson and co-workers, in which patients with suboptimal graft function transplanted 6 months to 8 years earlier were randomized to either remain on a CNI-based protocol (n = 19) or switch to a sirolimus-based regimen (n = 19). At 3 and 12 months, the GFR of patients who had switched to sirolimus had improved, such that it significantly exceeded that of the control group (P <0.001).

Despite reporting a relatively high incidence of adverse events in sirolimus-treated patients—including herpes zoster infection, proteinuria, hyperlipidemia, rashes and mouth ulcers—the authors of both studies contend that long-term follow up of CNI-free immunosuppression in kidney transplantation is warranted.