New targets for immunosuppression in kidney transplantation: Focus on recent clinical trials

Significant advances have been made in post-kidney transplantation immunosuppression. The introduction of calcineurin inhibitors (CNIs) has led to a reduction in acute rejection and improved 1-year outcomes. However, long-term allograft survival has not improved. This may in part be due to the chronic nephrotoxicity of CNIs and negative effects on the cardiovascular and metabolic risk profile via worsening hypertension, diabetes, and dyslipidemia. New drug development now focuses on maintaining low rejection rates but maximizing long-term allograft survival and modulating the cardio-metabolic side effects seen with CNIs. Two small molecules are currently undergoing Phase 2 investigation. CP-690550 (tasocitinib) is a JAK 3 inhibitor, and AEB-071 (sotrastaurin) is a protein kinase C inhibitor. Two biologic agents are also undergoing development. Belatacept is a humanized antibody that blocks the T-cell co-stimulation pathway and has had promising results in both Phase 2 and 3 investigation. Alefacept is a humanized antibody that inhibits T-cell adhesion and is currently undergoing Phase 2 investigation. This article will review the mechanisms of these drugs and outline the available trial data results.