Background: Belatacept (bela) might be an alternative to Calcineurin Inhibitors (CNI) in order to avoid presumed nephrotoxicity. In this study we assessed the impact of bela conversion in a cohort of American kidney transplant patients (KT).

Methods: EBV seropositive adult patients were converted to bela from tacrolimus, based upon our prior published protocol, usually for biopsy proven acute CNI toxicity and/or interstitial fibrosis/tubular atrophy. A majority of patients (N=29; 71%) underwent a surveillance biopsy usually within 6-10 months of conversion. A subset of pre- and post-conversion biopsies underwent transcriptome analysis using the MMDx platform.

Results: Forty-one (mean age=45 years) patients were switched to bela at a median of 6 months post-KT. Many were sensitized (32%; cPRA range=29-100%); regrafts (22%); had delayed graft function (56%); and had a history of acute rejection (22%). Death-censored graft survival was 88% at a mean follow-up of 3.4 years post-conversion. Of the five grafts (12%) that failed, three were lost at least partly due to acute T-cell mediated rejection (TCMR). Surveillance biopsies revealed 2 additional cases of subclinical TCMR, giving an overall rejection rate of 12%. Overall, renal function improved from a peak mean serum creatinine (SCr) of 2.9±1.6mg/dL to 2.6±1.7mg/dL at 6 weeks (p=0.03), and 2.3±0.9mg/dL at 3 months (p=0.004). This improvement was sustained with a SCr of 2.4±1.6mg/dL at most recent follow-up. Paired pre- and post-conversion histologic analysis did not reveal significant worsening of microvascular inflammation or chronicity. Transcriptome analysis of a subset of patients (N=20) did not reveal any significant changes in markers of acute kidney injury, either in inflammation or in parenchymal injury transcripts.

Conclusions: In this study we demonstrate that belatacept conversion might be safe for KT patients, including those at high-immunologic risk. Paired biopsy analysis revealed no significant histologic or molecular changes overtime. Since renal function improved early and then stayed stable, it is possible that the primary reason for improvement is vasomotor, rather than a true change in fibrogenesis. Given the absence of reduction in molecular injury markers after conversion, the presence of CNIs might not, in of itself, induce parenchymal injury.

CITATION INFORMATION: Sanghi P, Gupta G, Kumar D, Reeve J, Levy M, Sharma A, Fattah H, Kimball P, Massey H, King A, Halloran P. Impact of Belatacept Conversion on Kidney Transplant Function, Histology and Gene Expression. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress