The impact of calcineurin inhibitors on graft survival

Abstract

The discovery of the first calcineurin inhibitor (CNI), cyclosporine, represents a watershed event in the history of immunosuppression, as it was the first drug shown to reversibly inhibit T-lymphocyte function, therefore allowing for one of the major breakthroughs in modern medicine, that of organ transplantation. Calcineurin inhibitors remain the most effective and widely used immunosuppressive agents in organ transplantation today. The 2010 OPTN/SRTR Annual Report showed that 96% of renal transplant recipients were on CNI at the time of discharge from hospital. The prolonged use of CNI, however, may result in renal toxicity, renal dysfunction and eventual renal failure in both recipients of renal and other solid organ transplants, as well as in patients treated with these agents for autoimmune diseases. This brief review, while acknowledging that CNI toxicity does indeed exist, will focus on the successful use of CNI in renal transplant recipients, highlighting recent observations that provide alternative explanations for some of the adverse outcomes that have been attributed to CNI nephrotoxicity in the past.

Keywords: BPAR; Biopsy-proven acute rejection; CNI; Calcineurin inhibitors; CsA; Cyclosporine; DSA; Donor-specific antibodies; GIF; Graft interstitial fibrosis; Late graft failure; MMF; Mycophenolate mofetil; NODAT; Nephrotoxicity; New-onset diabetes after transplantation; TAC; Tacrolimus.