Effect of an Early Switch to Belatacept Among Calcineurin Inhibitor–Intolerant Graft Recipients of Kidneys From Extended‐Criteria Donors

Abstract

Transplant recipients receiving a kidney from an extended-criteria donor (ECD) are exposed to calcineurin inhibitor (CNI) nephrotoxicity, as demonstrated by severe delayed graft function and/or a low GFR. Belatacept is a nonnephrotoxic drug that is indicated as an alternative to CNIs. We reported 25 cases of conversion from a CNI to belatacept due to CNI intolerance within the first 6 mo after transplantation. The mean age of the recipients was 59 years, and 24 of 25 patients received ECD kidneys. At the date of the medication switch, 12 of 25 patients displayed a calculated GFR (cGFR) <15 mL/min, six patients remained on dialysis, and the biopsies showed evidence of acute tubular damage associated with severe vascular or tubulointerstitial chronic lesions. Three patients did not recover renal function, and three patients died during the follow-up period. Among the remaining patients, renal function improved: The cGFR was 18.28 AE 12.3 mL/min before the medication switch compared with 34.9 AE 14.5 mL/min at 1 year after conversion to belatacept (p = 0.002). Tolerance of and compliance with belatacept were good, and only one patient experienced acute rejection. Belatacept is an effective therapy that preserves renal function in kidney transplant patients who are intolerant of CNIs.

Belatacept after kidney transplantation in adolescents: a retrospective study

“…Switching to belatacept has been shown to increase GFR, in general regardless of time after KTx or of GFR at the beginning of belatacept treatment . These positive effects of belatacept on graft function, even on patients with normal adherence, can obviously also be expected in adolescents with nonadherence to oral immunosuppressive therapy.…”

Short-Term Intensified Dosage Regimen of Mycophenolic Acid is Associated with Less Acute Rejection in Kidney Transplantation from Donation after Circulatory Death

“…Previous studies showed that MPA exposure decreased in patients with DGF [17,18]. Owing to nephrotoxicity, high exposure to calcineurin inhibitors (cyclosporine or tacrolimus) was restricted in patients with DGF [19][20][21]. An increased early exposure to MPA might aid in reducing the need for high exposure to calcineurin inhibitors.…”

Abatacept as rescue immunosuppression after calcineurin inhibitor treatment failure in renal transplantation

“…To date, alternative immunosuppressive strategies to circumvent CNI intolerance in kidney transplant recipients have included CNI minimization, discontinuation, or conversion to alternative agents . With the advent of costimulation blockade and its favorable toxicity profile and improved long‐term outcomes, more recent approaches have successfully utilized belatacept in both stable, low‐risk renal transplant recipients and more unstable, high‐risk patients with CNI toxicity, renal dysfunction, or prolonged DGF . However, to our knowledge, no reports exist on the use of abatacept in solid organ transplantation de novo or as conversion rescue therapy for CNI intolerance.…”

“…Costimulation blockade with belatacept, a second‐generation form of CTLA‐4‐Ig or abatacept, was US Food and Drug Administration approved in 2011 as a CNI alternative for maintenance immunosuppression following kidney transplantation . Belatacept has been successfully utilized in stable, low immunologic risk renal transplant recipients converted off CNI therapy with improvement in renal function and a low rate of rejection, and several reports have documented its use as rescue therapy in CNI‐intolerant recipients or those with prolonged DGF . However, despite belatacept's potential as an option for rescue therapy in renal transplant recipients, its future has been uncertain due to higher rates of acute rejection and recent unavailability for de novo clinical use as a result of a production shortage.…”