Impact of belatacept conversion on kidney transplant function, histology, and gene expression ‐ a single‐center study. (7th September 2020)

• Record Type: Journal Article
• Authors: Gupta, Gaurav; Raynaud, Marc; Kumar, Dhiren; Sanghi, Pooja; Chang, Jessica; Kimball, Pam; Kang, Le; Levy, Marlon; Sharma, Amit; Bhati, Chandra S.; Kamal, Layla; Yakubu, Idris; Massey, Hugh D.; Kidd, Chelsea; King, Anne L.; Halloran, Philip F.
• Is Part Of: Transplant international. Volume 33:Number 11(2020)
• Page Start: 1458
• Page End: 1471
• Publication Date: 2020-09-07
• Subjects: belatacept -- calcineurin inhibitors -- immunosuppression -- immunosuppression clinical -- kidney clinical -- molecular diagnostics -- novel immunosuppressants; Transplantation of organs, tissues, etc -- Periodicals; 617.95405
• DOI: 10.1111/tri.13718
• Languages: English
• ISSNs: 0934-0874

Abstract

Abstract: Prior studies on belatacept conversion from calcineurin inhibitor (CNI) have been limited by an absence of postconversion surveillance biopsies that could underestimate subclinical rejection, or a case‐controlled design. A total of 53 adult patients with allograft dysfunction underwent belatacept conversion (median: 6 months) post‐transplant. At a median follow‐up = 2.5 years, patient survival was 94% with a death‐censored graft survival of 85%. Seven (13%) patients had acute rejection (including 3 subclinical) at median 6 months postconversion. Overall, eGFR improved ( P = <0.001) from baseline = 31±15 to 40.2 ± 17.6 ml/min/1.73m 2 by 6 months postconversion, but then stayed stable. This improvement was also observed ( P < 0.001) in comparison with a propensity matched control cohort on CNI, where eGFR stayed stable (mean ~ 32ml/min/1.72m 2 ) over 2‐year follow‐up. Patients converted < 6 months post‐transplant were more likely to have a long‐term improvement in kidney function. Paired gene expression analysis of 30 (of 53) consecutive pre‐ and postconversion surveillance biopsies did not reveal changes in inflammation/acute injury; although atrophy–fibrosis score worsened (mean = 0.28 to 0.44; P = 0.005). Thus, improvement in renal function with belatacept conversion occurred early and then sustained in comparison with controls where renal function remained unchanged overtime. We were unable to show molecular signals that could be related to CNI administration and regressed after withdrawal.