Calcineurin inhibitor sparing immunosuppressive regimens in kidney allograft recipients

Calcineurin inhibitors (CNI), cyclosporine and tacrolimus, have had a potent impact on the success of organ transplantation. However, the nephrotoxicity associated with CNI can cause renal dysfunction, which is an independent risk factor for graft loss and mortality after kidney transplantation (KTx). Thus, the search for an optimal immunosuppressive therapy continues to be crucial in KTx. Strategies to limit CNI exposure include CNI minimization, avoidance, and withdrawal. We conducted a literature review (PubMed, Medline) on this issue. Maximum reduction in CNI is associated with a modest improvement in renal function; however, the kidney damage is observed as long as CNIs are maintained. Avoidance of CNI is associated with high acute rejection rates. CNI withdrawal may be the optimal strategy because it reduces early immuno logic graft injury after KTx, particularly when CNI withdrawal is initiated before irreversible renal damage. These strategies seem feasible with mycophenolate acid, sirolimus and induction therapy with inter leukin-2 receptor antibodies as concurrent immunosuppressants.