Nephrotoxicity of immunosuppressive drugs: Long-term consequences and challenges for the future

The calcineurin inhibitors cyclosporin A (CsA) and tacrolimus (FK506) are a ssociated with dose- and efficacy-limiting adverse events, including nephro toxicity, which may diminish their overall benefits for long-term graft sur vival. Nephrotoxicity is difficult to distinguish from chronic allograft re jection and is a particular problem in the setting of renal transplantation . Minimizing immunosuppressant-induced nephrotoxicity could improve long-te rm renal allograft survival. However, to obtain significant long-term impro vement in renal allograft outcomes, it may be necessary to adopt new immuno suppressive regimens that rely less on calcineurin inhibitors. Recipients o f other transplanted organs, as well as patients with autoimmune diseases w ho require immunosuppressant therapy, could also benefit from this change i n immunosuppressive drug strategy because their healthy, native kidneys are particularly susceptible to the nephrotoxic effects of CsA and FK506, CsA- and FK506-sparing regimens, which use reduced doses of CsA and FK506 in co mbination with other nonnephrotoxic immunosuppressants, may be the best cur rent option for reducing nephrotoxicity. The chemical immunosuppressant myc ophenolate mofetil (MMF) has been used as part of CsA- and FK506-sparing re gimens that provide improved renal function while maintaining adequate immu nosuppression, Such regimens should reduce patient morbidity and mortality. Also, because immunosuppressant-induced nephrotoxicity has been associated with significant financial costs, CsA- and FK506-sparing regimens should r esult in substantial savings in health care costs. (C) 2000 by the National Kidney Foundation, Inc.