Use of belatacept in kidney transplantation: what's new?

Abstract

Purpose of reviewThe advent of calcineurin inhibitors have led to a significant improvement in short term outcomes after kidney transplantation. However, long term outcomes are hindered by the cardiovascular, metabolic and chronic renal toxicity associated with these agents. Belatacept is a selective T cell costimulation blocker that is approved for prevention of rejection in kidney transplantation, and has been associated with favorable cardiovascular, metabolic and renal outcomes in kidney transplant recipients. This review provides an overview of recent updates in the use of belatacept in kidney transplant recipients.Recent findingsBelatacept may be a safe alternative to calcineurin inhibitors for select kidney transplant populations. Patients converted to belatacept from a calcineurin inhibitor-based immunosuppression generally experience improvement in renal function, and may be less likely to develop de novo donor specific antibodies or new onset diabetes after transplantation. Although, belatacept based immunosuppression may increase the risk of early acute cellular rejection, it may however be beneficial in stabilization of long-term renal function and improvement in inflammation in patients with chronic active antibody mediated rejection. These benefits need to be counterweighed with risks of lack of response to severe acute respiratory syndrome coronavirus 2 vaccination and other adverse infectious outcomes.SummaryBelatacept may be an alternative to calcineurin inhibitors and may contribute to improved long term metabolic and allograft outcomes in kidney transplant recipients. Careful selection of patients for belatacept-based immunosuppression is needed, to obviate the risk of acute rejection shown in clinical studies.

Management of kidney transplant recipients for primary care practitioners

“…Of note, there have been reports of increased incidence of cytomegalovirus infection, slower viral clearance, and ganciclovir-resistance. Its use is contraindicated in patients seronegative to EBV given the risk of posttransplant lymphoproliferative disorder [ 27 ].…”

Back to the Future With Co-Stimulation Blockade

“…Belatacept, a fusion protein of the Fc fragment of a human IgG1 linked to the extracellular domain of CTLA-4 [ 6 ] was engineered to overcome slightly weaker binding avidity to CD80/86 of the progenitor molecule Abatacept, which differs just by 2 amino acids. These changes increased in vitro T-cell inhibitory activity and demonstrated superior protection from allograft rejection in pre-clinical models but were limited to the i.v.…”

“…formulation of Belatacept. Extensive clinical trials and followups have confirmed the efficacy of Belatacept for kidney transplantation [6][7][8], and the drug is often employed as a substitute or conversion agent to overcome intolerance to CNIs. Common reasons for switching include nephrotoxicity, thrombotic microangiopathy, posterior reversible encephalopathy syndrome, reducing cardiovascular risk factors, etc.…”