Immunosuppression after renal transplantation

Abstract

Immunosuppression (IS) is administered to kidney transplant recipients to prevent rejection episodes and loss of the renal allograft. Most centers rely on a triple IS after induction with either interleukin‑2 receptor antibodies or antithymocyte globulin. The most frequently used substances for maintenance IS are glucocorticoids, antimetabolites, mTOR inhibitors (mTORi), calcineurin inhibitors (CNI) and the costimulation blocker belatacept. Guidelines recommend a triple combination consisting of CNIs, antimetabolites and corticosteroids for the majority of patients. The long-term risk for malignancy in general is increased in solid organ recipients compared to the general population. Modification of IS may result in reduced risk for non-melanoma skin cancers but results in higher graft rejection rates and in the case of mTORi, deaths. In the case of posttransplantation lymphoproliferative disorders (PTLD) treatment options are reduction of IS, rituximab, chemotherapy, radiation therapy or a combination of these. The optimal protocol has not yet been established and depends on patient age and status, tumor load, laboratory findings, organ functions (heart, kidney, liver) and PTLD subtype. Posttransplantation diabetes mellitus is a frequent complication after kidney transplantation. Tacrolimus more than cyclosporine A, sirolimus and corticosteroids are considered to be diabetogenic; however, tacrolimus remains the first choice as the mainstay of IS. In general, the IS regimen should be tailored for optimal kidney allograft survival rather than better diabetic control. Concerning infections, cytomegalovirus and Pneumocystis jerovecii are best managed by prophylaxis. In the case of virus reactivation or opportunistic infections, targeted therapy is applied and the net state of IS is most often reduced.