Rationale for using belatacept in combination with sirolimus

Kidney transplantation can be used to replace failing native kidneys; however, it requires long-term immunosuppression, and immunological tolerance for this is not yet achievable. The cornerstone of immunosuppression is based on calcineurin inhibitors, which are nephrotoxic. Therefore, new drugs are being developed that provide efficacious immunosuppression and almost no renal toxicity. The first family of drugs that have these properties are mammalian target of rapamycin inhibitors: these include sirolimus and everolimus. These two drugs, besides their immunosuppressive properties, also have beneficial effects regarding cytomegalovirus (CMV) infection, which is a very common posttransplantation complication. In phase III trials, belatacept, a costimulatory blocker, has also been shown to provide a good immunosuppressive effect and also gives a significantly better cardiovascular profile than cyclosporine-based immunosuppression. However, belatacept can potentially increase infections such as CMV. Thus, herein, we describe the rationale for combining belatacept with sirolimus for kidney transplant patients.