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.
Highlights
Transplantation is the treatment of choice for end stage organ failure
EGFR increased by 1.9 ml/min/ 1.73 m2 per year in the group switch to a belatacept-based immunosuppression regimen compared to 0.07 ml/min/1.73 m2 in the group who remained on a calcineurin inhibitors (CNIs)-based regimen (p = 0.01)
Progressive chronic kidney disease is a well-known complication of all solid organ transplants
Summary
Transplantation is the treatment of choice for end stage organ failure. In non-renal solid organ transplants, with no replacement therapies, transplantation is a lifesaving procedure. The leading causes of death and graft loss are cardiovascular disease and chronic allograft nephropathy [9]. These drugs that are the mainstay of modern day immunosuppression contribute to cardiovascular mortality due to their deleterious effects on blood pressure, dyslipidemias, and diabetes [10]. Five years after transplantation histological evidence of CNI induced nephrotoxicity is seen in greater than 50% of allografts, and by 10 years, this finding is universal [12] Many alternative regimens such as CNI minimization, withdrawal and avoidance with use of mammalian target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) have been tried but rejection risks are higher, and sustained improvement in kidney function has not been seen consistently across different studies [13,14,15]. Belatacept (Bristol-Myers Squibb, New York, NY, USA), a molecule that blocks T cell costimulation, has shown promise in both short- and long-term renal transplant outcomes with a superior side-effect profile compared to CNIs [16]
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