Update on costimulatory blockade in transplantation: a review of recent literature

PURPOSE OF REVIEW: Calcineurin inhibitors (CNIs) and steroids remain the major components of immunosuppressive regimens despite long-term side effects including nephrotoxicity and derangements in metabolic parameters. Belatacept, the first costimulatory blockade molecule approved for prophylaxis of kidney transplant rejection, has been shown to improve renal function over long-term use compared with CNIs, though concerns regarding increased rates of acute rejection has limited its widespread use. This update describes the initial development of belatacept and costimulation blockade; reviews the current state of its use as a clinically applicable immunosuppressant; and discusses the future direction of costimulation blockade and its use with newly emerging immunosuppressive strategies. RECENT FINDINGS: Iterative refinements to belatacept-containing protocols have reduced the incidence of acute rejection to rates comparable to those seen in CNI-based regimens, while preserving both a glomerular filtration rate advantage as well as improvements in long-term patient and graft survival. Increasingly sophisticated mechanistic understanding of immunology has allowed belatacept to be combined with newly developed, targeted therapies to expand its use. Transplant of organs other than kidney have begun to use belatacept with encouraging results. SUMMARY: Belatacept offers significant advantages in kidney transplantation, minimizing the negative effects of steroids and CNIs. New combinations with standard and emerging medications, along with new indications and clinical applications, continues to widen its use and allow increasing access.