Date: Monday, June 3, 2019
Session Time: 4:30pm-6:00pm
Presentation Time: 4:42pm-4:54pm
Location: Veterans Auditorium
*Purpose: Switching from CNI- to Belatacept-based regimen has been associated with improved graft function in low-immunologic risk kidney recipients. We investigated the efficacy and safety of conversion to Belatacept in kidney recipients with post-transplant anti-HLA DSAs.
*Methods: We prospectively included 109 adult kidney recipients with post-transplant anti-HLA DSAs and biopsy-proven CNI nephrotoxicity who were converted to Belatacept (2012-2017). We excluded patients with acute AMR. Patients were systematically assessed for clinical and histological characteristics and DSA characteristics (specificity, MFI and IgG subclass composition using SAB) at the time of conversion and one year post-conversion, and compared to 109 historical controls receiving MMF, CNIs and corticosteroids transplanted between 2002 and 2016 identified by propensity score matching (overall n=5211). Patients were followed-up to 2018 to evaluate graft survival and adverse events.
*Results: Patients were converted at a median time of 13.0 (IQR, 3.0-66.1) months post-transplant and showed improved GFR at one year (39.8±14.4 vs. 29.5±13.9 mL/min, p<0.001), while controls showed stable GFR (28.7±14.5 vs. 29.2±14.3 mL/min, P=0.80). Converted patients exhibited decreased DSA MFImax levels at one year post-switch (4624±5398 vs. 5320±5553, p<0.001), while control patients had stable MFImax levels (5184±5712 vs. 5365±5510, p=0.81). Among converted patients, prevalence of complement-fixing IgG1 and IgG3 subclasses diminished from 38.5% to 26.6% under Belatacept treatment (p=0.002). Histologically, converted patients showed decreased prevalence of microcirculation inflammation (g>0 and/or ptc>0, 15.6% vs. 22.9%, p=0.027) and of C4d deposition (16.5% vs. 29.4%, p=0.004) at one year post-conversion. Converted patients showed similar incidences of adverse events compared with controls.
*Conclusions: Conversion from CNI- to Belatacept-based regimen in kidney recipients with post-transplant anti-HLA DSAs and nephrotoxicity is safe and associated with improved graft function and decreased pathogenicity of anti-HLA DSAs evidenced by the kinetics of their characteristics and of allograft injury.
To cite this abstract in AMA style:Louis K, Viglietti D, Pievani D, Aubert O, Glotz D, Legendre C, Zeevi A, Loupy A, Lefaucheur C. Conversion from Calcineurin Inhibitors to Belatacept in Kidney Recipients with Donor-Specific Anti-HLA Antibodies and Calcineurin Inhibitor Nephrotoxicity Decreases the Pathogenicity of Donor-Specific Anti-HLA Antibodies [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/conversion-from-calcineurin-inhibitors-to-belatacept-in-kidney-recipients-with-donor-specific-anti-hla-antibodies-and-calcineurin-inhibitor-nephrotoxicity-decreases-the-pathogenicity-of-donor-specific/. Accessed March 5, 2021.
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