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Analysis of Rejection, Rejection Therapy and Renal Function in the BEST Trial

H. Kuzaro1, A. R. Shields2, A. Wiseman3, S. Tremblay1, A. Christianson1, D. Kaufman4, J. Leone5, A. Matas6, P. West-Thielke7, R. R. Alloway1, E. S. Woodle1

1U Cincinnati, Cincinnati, OH, 2The Christ Hospital, Cincinnati, OH, 3U Colorado, Denver, CO, 4U Wisconsin, Madison, WI, 5Tampa General, Tampa, FL, 6U Minnesota, Minneapolis, MN, 7UIC, Chicago, IL

Meeting: 2020 American Transplant Congress

Abstract number: 456

Keywords: Co-stimulation, Immunosuppression, Kidney, Rejection

Session Information

Date: Saturday, May 30, 2020

Session Name: Kidney: Acute Cellular Rejection

Session Time: 3:15pm-4:45pm

 Presentation Time: 3:15pm-3:27pm

Location: Virtual

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*Purpose: The BEST Trial (Belatacept-based Early Steroid Withdrawal) compared two belatacept (BELA)-based early corticosteroid withdrawal (ESW) regimens and alemtuzumab (ALEM) or rabbit antithymocyte globulin (rATG) induction with a tacrolimus (TAC)-based ESW regimen and rATG induction. The purpose of this study was to compare the impact of rejection on renal function in BELA-treated pts vs TAC-treated pts.

*Methods: Pts with biopsy-proven acute rejection (BPAR) were identified. Protocol treatment of BPACR Banff IA or IB was high dose CS with a taper; BPACR >IIA, was rATG for 7-14 days of CD3 suppression. TAC rescue (10-15 ng/mL goal trough) was used for AR refractory to CS or rATG. Rejection reversal was defined as return of serum creatinine to 115% of baseline or histologic reversal. Data analysis was performed using descriptive statistics.

*Results: Outcomes of pts with and without BPAR are in Table 1. 53 BPAR episodes were reported: ALEM/BELA (Grp A n=20/107, 18.7%), rATG/BELA (Grp B n=26/104, 25%) and rATG/TAC (Grp C n=7/105, 7%). There was significantly more early BPAR in Grp A vs B (p=0.006). BPACR was more frequent in Grp B vs C (p=0.009) with first BPACR >IIA in Grp B greater than Grp C (p=0.032) (Table 2). In African American pts, BPAR was significantly more frequent in Grp B vs A (p=0.002). Grps A and B had 20% and 23.1% steroid resistant BPAR respectively compared to 0% in Grp C. eGFR values were similar in BPAR pts, however renal function was better in pts without BPAR, particularly in BELA groups. For pts without BPAR, a higher % of pts with low eGFR (eGFR <45 ml/min/1.73m2) at 24 mos was observed in Grp C vs B (p=0.001). For pts without BPAR, proteinuria was more common in Grp C vs B (p=0.003). BELA treated pts (Grps A and B) with BPAR who remained on BELA experienced higher eGFRs with a reduced % of pts with eGFR <45ml/min at 24 mo (Table 3). Pts with BPAR in Grp A or B who were converted to TAC-based regimens experienced lower eGFRs similar to those with BPAR in Grp C. Graft and patient survival were similar between groups. The majority of BPAR pts in Grp A and B continued on a BELA-based regimen.

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*Conclusions: BPAR was associated with worse renal function irrespective of treatment regimen, but was more evident in TAC pts and in BELA pts who were converted to a TAC-based regimen. Longer-term observations are required to determine if the impact of BPAR on renal function is overcome when a BELA-based regimen is maintained.

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To cite this abstract in AMA style:

Kuzaro H, Shields AR, Wiseman A, Tremblay S, Christianson A, Kaufman D, Leone J, Matas A, West-Thielke P, Alloway RR, Woodle ES. Analysis of Rejection, Rejection Therapy and Renal Function in the BEST Trial [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/analysis-of-rejection-rejection-therapy-and-renal-function-in-the-best-trial/. Accessed March 8, 2021.

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