*Purpose: Chronic active antibody mediated rejection (cABMR) is a major cause of long-term kidney transplant (KT) loss. Current therapies have unclear efficacy and significant side effects. Basic and clinical science data suggests that belatacept might alter germinal center responses and improve renal function in patients with chronic allograft dysfunction with chronic interstitial fibrosis/tubular atrophy (IFTA).

*Methods: 19 patients with biopsy-proven cABMR+IFTA were converted to belatacept with a modified tacrolimus taper performed over 12 weeks. All patients underwent pre- and post-conversion biopsies and also underwent transcriptome analysis using the molecular microscope (MMDx). The trend and slope of eGFR post-conversion was compared to a 1:2 propensity matched control cohort of cABMR patients. This cohort had been treated with rituximab/IVIg, maintained on Calcineurin Inhibitor (CNI) based immunosuppression and derived from the Paris Transplant Group (PTG) registry (N=38; matched on clinical and histological variables).

*Results: Patients (mean age: 45years) were converted from tacrolimus to belatacept at a median of 44 months post-KT. At a median follow-up of 22 months (range=7-40), renal function trended towards improvement from a mean eGFR of 34±10 ml/min/1.73m2 to 39±16 ml/min/1.73m2 (p=0.15) while proteinuria remained unchanged (1.3±1.1 mg/mg vs 1.6±1.6 mg/mg; p=0.62). At most recent follow-up, there were no cases of acute rejection with a death-censored graft and patient survival of 89% and 95%, respectively. When compared to the matched PTG cohort, the belatacept group had a significant improvement (p=0.02) in GFR from a mean of 33.9±10 at baseline to 37.8±13 at 6 months and 38.5±12 ml/min/1.73m2 at 12 months post conversion, as compared to a steady decline noted in the PTG group [36.2 (baseline) to 33.1 (6 months) to 32 ml/min/1.73m2 (12 months)]. A paired histologic comparison of pre- and post-conversion biopsies showed no worsening in MVI (G+PTC) and chronicity (CI+CT+CG+CV) scores. A paired MMDx comparison showed a trend towards improvement in mean total rejection (0.68 to 0.56; p=0.02), ABMR (0.64 to 0.56; p=0.06), PTC (0.67 to 0.58; p=0.05), and glomerulitis (0.63 vs 0.53; p=0.06) scores.

*Conclusions: In this first report, we find that in patients with cABMR who were not recently subjected to intensive immunosuppressive therapies, belatacept conversion was associated with an improvement in renal function. These results are further bolstered by molecular evidence of improved microvascular inflammation and rejection scores on follow-up biopsies as well as an improvement in renal function when compared to a propensity-matched control group maintained on CNI therapy.

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