Session Time: 3:15pm-4:45pm
Presentation Time: 4:03pm-4:15pm
*Purpose: Chronic active antibody mediated rejection (cABMR) is a major cause kidney transplant (KT) loss. Current therapies have unclear efficacy and side effects. Basic and clinical science data suggests that belatacept may alter germinal center responses and improve renal function in patients with chronic allograft dysfunction. We have previously presented our experience with belatacept conversion and comparison of eGFR trend with propensity matched controls. Here we present our extended experience with additional patients.
*Methods: 27 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 between 6-12 months post-conversion and also underwent transcriptome analysis using the molecular microscope (MMDx; ATAGC).
*Results: Patients (mean age: 44years) were converted from tacrolimus to belatacept at a median of 44 months post-KT. At a median follow-up of 27 months (range=11-56), renal function remained stable with a mean eGFR of 34±15ml/min/1.73m2 to 34±19ml/min/1.73m2 (p=0.79) and so did proteinuria (1.2±1.1mg/mg vs 1.3±1.6mg/mg; p=0.55). At the most recent follow-up, there were no new cases of acute rejection with a death-censored graft and patient survival of 89% and 93%, respectively. The average decline in eGFR from 12 months prior to conversion was -1.6±2.4ml/min/1.73m2. For the 12 months post conversion the slope stabilized and improved to 0.34±0.86 ml/min/1.73m2 (p=0.002). A paired histologic comparison of pre and post-conversion biopsies showed no worsening in microvascular inflammation (G+PTC) and chronicity scores. A paired MMDx comparison showed a trend towards improvement in mean total rejection (0.71±0.24 to 0.64±0.31; p=0.08), peritubular capillaritis score (0.70±0.20 to 0.64±0.28; p=0.09), and glomerulitis (0.66±0.23 vs 0.60±0.29; p=0.07) scores.
*Conclusions: In this extended report, we find that belatacept conversion in patients with cABMR not recently subjected to intensive immunosuppressive therapies; resulted in intermediate-term stability in renal function. This may translate to improved long-term outcomes in light of recent data that a 30% change in eGFR over 2 years can be used as a surrogate marker for long-term outcomes. These results are further bolstered by molecular evidence of improved microvascular inflammation and rejection scores.
To cite this abstract in AMA style:Kumar D, Yakubu I, Paluri S, Chachar A, Chang J, Moinuddin I, Kamal L, Levy M, Bhati C, King A, Kimball P, Halloran P, Gupta G. Impact of Belatacept Conversion on Renal Function, Histology and Gene Expression in Kidney Transplant Patients with Chronic Active Antibody-Mediated Rejection [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/impact-of-belatacept-conversion-on-renal-function-histology-and-gene-expression-in-kidney-transplant-patients-with-chronic-active-antibody-mediated-rejection-2/. Accessed December 5, 2020.
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