Tailoring tacrolimus-based immunotherapy in renal transplantation

Tacrolimus is a cornerstone immunosuppressive agent in renal transplantation and compared with ciclosporin, its use is associated with a reduced incidence of acute rejection. Optimizing immunosuppressive management in the early post-transplant period is important for achieving long-term graft function and survival. In attempts to improve the long-term outcomes of renal transplantation further, tacrolimus has been combined with two novel immunosuppressive agents, mycophenolate mofetil (MMF) and sirolimus, with encouraging results in terms of patient and graft survival, acute rejection rates and renal graft function. Tacrolimus in combination with MMF adjunctive therapy showed significantly better graft survival in patients with delayed graft function, fewer episodes of corticosteroid-resistant rejection and better renal function at the 3-year follow-up compared with ciclosporin microemulsion plus MMF immunosuppression. A tacrolimus plus MMF regimen was also effective for renal transplant recipients at our centre in Pennsylvania, resulting in excellent survival and rejection rates at I year post-transplantation. The 3-month results of a US multicentre study comparing tacrolimus in combination with either MMF or sirolimus showed these two treatment regimens to be equivalent in terms of patient and graft survival, delayed graft function, the incidence of biopsy-confirmed acute rejection and renal graft function, although differences were apparent in terms of acute tubular necrosis and hyperlipidaemia. In conclusion, the development of a new immunosuppressive regimen in renal transplantation should take account of factors that influence graft function, both in the short and long term, as a way of optimizing individual maintenance therapy.