P SANGHI1, P HALLORAN2, D KUMAR1, J REEVE2, M LEVY1, A SHARMA1, H FATTAH1, P KIMBALL1, HD MASSEY1, AL KING1, G GUPTA1
1Virginia Commonwealth University, Richmond, USA; 2Alberta Transplant Applied Genomics Center, Edmonton, Canada
Background: Belatacept (bela) might be an alternative to Calcineurin Inhibitors (CNI) in order to avoid nephrotoxicity. In this study we assessed the impact of bela conversion in a cohort of kidney transplant patients (KT).
Methods: EBV seropositive adult patients were converted to bela from tacrolimus, as per our protocol, for biopsy proven interstitial fibrosis/tubular atrophy. A majority of patients (N=29; 71%) underwent a surveillance biopsy within 6 months of conversion. A subset of pre- and post-conversion biopsies underwent transcriptome analysis (N=20) using the Molecular microscope system (MMDx).
Results: Forty-one (mean age=45 years) patients were switched to bela at a median of 6 months post-KT. Many were sensitized (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 allograft failures, three were lost partially due to acute rejection. The median time to conversion was 5.6 months and median time on bela was 17months.
Renal function improved from an eGFR of 31.6±15.8ml/min/1.73m2 to 38.7±17.7ml/min/1.73m2 at 3 months (p=0.003) post conversion. This improvement was sustained with an eGFR of 40.7±15.8ml/min/1.73m2 at most recent follow-up (p<0.001). Paired pre- and post-conversion histologic analysis did not reveal any worsening of microvascular inflammation or chronicity. Similarly, MMDx analysis did not reveal any significant changes in markers of acute kidney injury.
Conclusions: In this study we demonstrate that belatacept conversion might be safe for KT patients, including the high-immunologic risk group. 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.