*Purpose: Prior studies on the conversion of tacrolimus (Calcineurin Inhibitor; CNI) to belatacept have been limited in scope due to either the absence of, post-conversion surveillance biopsies that could underestimate rejection rates, or a case-controlled design that makes attribution of improvement in kidney function to belatacept difficult.

*Methods: 53 adult kidney transplant (KT) patients were converted to belatacept from tacrolimus for allograft dysfunction. The slope of eGFR post-conversion was compared to a 1:3 propensity matched cohort of patients maintained on CNI (N=159; matched on clinical and histologic variables) derived from the Paris Transplant Group (PTG) registry. Most patients (N=37; 70%) underwent a post-conversion surveillance (at median 6 months) biopsy. Thirty (57%) consecutive patients also underwent transcriptome analysis of pre- and post-conversion biopsies using the molecular microscope (MMDx).

*Results: Patients (mean age: 48 years) were switched to belatacept at a median of 6 months post-KT. Many were sensitized (32%; cPRA range=29-100%); re-grafts (23%); had delayed graft function (60%); and had a history of recent acute rejection (15%). Death-censored graft survival was 85% at a median follow-up of 2.5 years post-conversion. Seven (13%) patients had TCMR (at median=6 months) post-conversion. Of these, two were subclinical TCMR. Overall, renal function improved (p=<0.001) from a peak mean eGFR of 31±15 to 38±17 mL/min/1.72m2 by 6 months post-conversion, but then stayed stable till most recent follow-up. This eGFR improvement was also observed (p<0.001) in comparison to the matched PTG cohort where eGFR did not improve overtime but stayed stable (mean~32mL/min/1.72m2) up till a comparative time-frame of 2 years. Paired pre- and post-conversion histologic analysis did not reveal worsening of inflammation or chronicity. Paired biopsy gene expression analysis also did not reveal significant changes in inflammation or acute kidney injury; although the atrophy-fibrosis score worsened (mean=0.28 to 0.44; p=0.005). An in-depth analysis of individual genes also did not reveal any patterns of improvement after belatacept conversion.

*Conclusions: In this study we report that belatacept conversion was safe for kidney transplant patients, including those at high-immunologic risk. Improvement in renal function with belatacept conversion was seen early and then sustained in comparison to a matched control cohort where there was neither an improvement nor worsening in renal function overtime. Of interest, the withdrawal of CNIs did not lead to any reduction of molecular injury features. Moreover, we were unable to show any molecular signals that could be related to CNI administration and regressed after withdrawal.

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