Belatacept Conversion in Kidney After Liver Transplantation

Abstract

Background. Costimulatory blockade with belatacept has demonstrated long-term benefits in renal transplantation, but de novo use in liver transplant recipients has resulted in increased rejection, graft loss, and death. However, belatacept conversion as a calcineurin inhibitor (CNI) avoidance strategy has not been studied and may be of benefit in liver transplantation where CNI-induced renal dysfunction and toxicity are barriers to improved outcomes. Methods. Using clinical data extracted from our institutional medical record, we report on 8 patients who underwent kidney after liver transplantation and were treated with belatacept-based immunosuppression and transient CNI therapy. Results. All patients tolerated belatacept therapy without any patient deaths or graft losses. No episodes of rejection, de novo donor-specific antibody formation, or major systemic infections were observed, and all patients demonstrated preserved liver and excellent renal allograft function. Patients received belatacept for a median duration of 13.2 mo, and at a median follow-up of 15.9 mo post–kidney transplant, 6 of 8 patients continued on belatacept with 3 completely off and 3 poised to transition off CNI. Conclusions. These findings are the first evidence that in liver transplant recipients requiring subsequent kidney transplantation, belatacept-based therapy can potentially facilitate CNI-free maintenance immunosuppression. This supports the possibility of belatacept conversion in stand-alone liver transplant recipients as a viable method of CNI avoidance.

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

“…Maintenance immunosuppression consisted of intra-operative belatacept, MMF 2000 mg/day, prednisone tapered to 5 mg daily and low-dose tacrolimus tapered off at 12 months posttransplant in the majority of patients. All patients had preserved kidney and liver allograft function, and no graft losses, patient deaths, rejection of liver of kidney allografts, or infectious complications reported [27 ▪ ]. These results suggest, that belatacept may be safe for kidney transplant patients with previous liver transplants in the context of a prolonged tacrolimus taper.…”

Costimulatory Blockade and Solid Organ Transplantation: The Past, Present, and Future

“…Although the initial multicenter trial of belatacept in liver transplant patients was terminated due to an increased risk of the composite outcome (rejection, graft loss, or death) within 6 months of transplant, 98 we reported the Emory experience with 8 patients who underwent kidney-after-liver transplantation who were treated with belatacept-based immunosuppression (in conjunction with transient CNI therapy). 99 No episodes of rejection, major systemic infection, or graft loss were observed, and all these patients demonstrated preserved liver and excellent renal allograft function, with 3 of the patients weaned completely off CNI and another 3 poised to transition off CNI at time of publication. Successful use of belatacept has also been published for kidney-after-heart transplantation, 100 isolated heart transplant, 101 and conversion trials in lung transplant recipients who developed renal insufficiency or hemolytic uremic syndrome on tacrolimus.…”

Targeting inflammation and immune activation to improve CTLA4-Ig-based modulation of transplant rejection

“…Moreover, a follow up study attempting to maintain the same patients on MMF monotherapy after Belatacept withdrawal indicated lack of operational tolerance, as patients experienced graft dysfunction following the switch (52). Other studies showed some benefits with Belatacept conversion as method for CNI withdrawal (53), or using Belatacept with MMF as bridge to CNI therapy (54).…”