Belatacept As an Alternative to Calcineurin Inhibitors in Patients with Solid Organ Transplants

Abstract

The goal of immunosuppression in transplantation has shifted to improving long-term outcomes, reducing drug-induced toxicities while preserving the already excellent short-term outcomes. Long-term gains in solid organ transplantation have been limited at least partly due to the nephrotoxicity and metabolic side effects of calcineurin inhibitors (CNIs). The alloimmune response requires activation of the costimulatory pathway for T cell proliferation and amplification. Belatacept is a molecule that selectively blocks T cell costimulation. In June 2011, the U.S. Food and Drug Administration approved it for maintenance immunosuppression in kidney transplantation based on two open-label, randomized, phase III trials. Since its introduction, belatacept has shown promise in both short- and long-term renal transplant outcomes in several other trials. It exhibits a superior side effect profile compared to CNIs with a comparable efficacy. Across all solid organ transplants, the burden of chronic kidney disease, its associated cardiovascular morbidity, mortality, and inferior patient/allograft survival is a well-documented problem. In this review, we aim to discuss the evidence behind the use of belatacept in solid organ transplants as an effective alternative to CNIs for renal rescue in patients with acute and/or chronic kidney injury.

A Friend or Foe: Calcineurin across the Gamut of Neurological Disorders

“… 166 Other diagnostic suggestions involve the requirement for more sensitive Doppler devices to monitor intracranial pressure noninvasively, monitoring of EEG levels post-transplant, and impaired verbal and motor responsiveness without electrolyte imbalance, tinnitus, or hearing loss (improved after discontinuation of tacrolimus). 167 Alternative therapies to CNI involve monoclonal antibodies (belatacept), 168 combinations of mycophenolate mofetil and sirolimus, 169 along with newer CNI-free therapies in the pipeline. 170 CNI-free immunosuppressant therapy may prove to be beneficial in organ transplant patients in the future.…”

The Conundrum of High Body Mass Index in Kidney Transplant Patients

“…Alternative new drugs as belatacept with better metabolic risk profile look promising in order to reduce drug-induced toxicities, such as hypertension and diabetes [29], with the potential of improving long-term renal function. Studies in de novo belatacept recipients have shown higher mean non-HDL cholesterol and lower mean triglycerides blood levels when compared to Calcineurin Inhibitor (CNI) treated patients [30]. Although this interesting preliminary evidence in favour of belatacept, we do not encourage a complete CNI withdrawal, since it is associated with a higher rate of rejection in comparison to tacrolimus, the most commonly used CNI [31].…”

Does Mineralocorticoid Receptor Antagonism Prevent Calcineurin Inhibitor-Induced Nephrotoxicity?

“…Adverse event rates were similar ( 12 ). The use of belatacept as an alternative to CNI in solid organ transplantation has been summarized in a recent review ( 14 ).…”