Efficacy and Safety Outcomes of Extended Criteria Donor Kidneys by Subtype: Subgroup Analysis of BENEFIT-EXT at 7 Years After Transplant

Abstract

The phase III Belatacept Evaluation of Nephroprotection and Efficacy as First-Line Immunosuppression Trial-Extended Criteria Donors Trial (BENEFIT-EXT) study compared more or less intensive belatacept-based immunosuppression with cyclosporine (CsA)-based immunosuppression in recipients of extended criteria donor kidneys. In this post hoc analysis, patient outcomes were assessed according to donor kidney subtype. In total, 68.9% of patients received an expanded criteria donor kidney (United Network for Organ Sharing definition), 10.1% received a donation after cardiac death kidney, and 21.0% received a kidney with an anticipated cold ischemic time ≥24 h. Over 7 years, time to death or graft loss was similar between belatacept- and CsA-based immunosuppression, regardless of donor kidney subtype. In all three donor kidney cohorts, estimated mean GFR increased over months 1-84 for belatacept-based treatment but declined for CsA-based treatment. The estimated differences in GFR significantly favored each belatacept-based regimen versus the CsA-based regimen in the three subgroups (p < 0.0001 for overall treatment effect). No differences in the safety profile of belatacept were observed by donor kidney subtype.

Keywords: calcineurin inhibitor: cyclosporine A (CsA); clinical research/practice; donors and donation: deceased; donors and donation: donation after circulatory death (DCD); donors and donation: extended criteria; immunosuppressant; kidney transplantation/nephrology.

Figure 1

Patient numbers by donor kidney subgroup and treatment allocation. CIT, cold ischemia time; CsA, cyclosporine; DCD, donation after cardiac death; ECD, expanded criteria donor; LI, less intensive; MI, more intensive; UNOS, United Network for Organ Sharing.

Figure 2

Kaplan–Meier curve for the composite end point of time to death or graft loss in the (A) UNOS ECD, (B) DCD, and (C) anticipated CIT ≥24 h cohorts. CI, confidence interval; CIT, cold ischemia time; CsA, cyclosporine; DCD, donation after cardiac death; ECD, expanded criteria donor; HR, hazard ratio; LI, less intensive; MI, more intensive; UNOS, United Network for Organ Sharing.

Figure 3

Estimated mean GFR for months 1–84 (mixed‐effects modeling without imputation) in the (A) UNOS ECD, (B) DCD and (C) anticipated CIT ≥24 h cohorts. Data represent means and 95% CIs. CI, confidence interval; CIT, cold ischemia time; CsA, cyclosporine; DCD, donation after cardiac death; ECD, expanded criteria donor; LI, less intensive; MI, more intensive; UNOS, United Network for Organ Sharing.