Impact of Belatacept Conversion on Renal Function, Histology and Gene Expression in Kidney Transplant Patients With Chronic Active Antibody-mediated Rejection.

Background Here, we present our initial experience with a prospective protocol of belatacept conversion in patients with caAMR and a high degree of chronicity at the time of diagnosis. Methods We converted 19 patients (mean age=45 ± 12 years) with biopsy-proven chronic active antibody mediated rejection (caAMR) from tacrolimus to belatacept at a median of 44 months postkidney transplant. Results At a median of 29 months (IQR: 16-46 months) postconversion, death-censored graft and patient survivals were 89% and 95%, respectively. When compared to a 1:2 propensity matched control cohort from the INSERM U970 registry maintained on Calcineurin Inhibitor (CNI), the belatacept group had progressive improvement (p=0.02) in estimated glomerular filtration rate from a mean of 33.9 ± 10 at baseline to 37.8 ± 13 at 6 months and 38.5 ± 12 ml/min/1.73m at 12 months postconversion, as compared to a steady decline noted in the controls [36.2 (baseline) ->33.1 (6 months) ->32.7 ml/min/1.73m (12 months) of follow-up]. A paired histologic comparison of preconversion and postconversion (performed at median 9.5 months postconversion) biopsies showed no worsening in microvascular inflammation or chronicity. The paired tissue gene expression analysis showed improved mean total rejection score (0.68 ± 0.26 to 0.56 ± 0.33; p=0.02) and a trend towards improved Amr score (0.64 ± 0.34 to 0.56 ± 0.39; p=0.06). These results are bolstered by molecular evidence of improved inflammation. Conclusions Here, we report that in patients diagnosed with caAMR who were not subjected to intensive salvage immunosuppressive therapies; isolated belatacept conversion alone was associated with stabilization in renal function.