Response to Treatment in Kidney Recipients with Acute T Cell-Mediated Rejection: Major Impact of Inflammation in Sclerotic Cortical Parenchyma (i-IF/TA) and Donor-Specific Antibodies

Y. Bouatou, D. Viglietti, D. Pievani, J. Duong Van Huyen, O. Aubert, D. Glotz, C. Legendre, A. Loupy, C. Lefaucheur

Paris Translational Research Center for Organ Transplantation, Paris, France

Meeting: 2019 American Transplant Congress

Abstract number: 425

Keywords: Graft failure, Kidney transplantation, Rejection

Session Information

Session Name: Concurrent Session: Kidney: Acute Cellular Rejection

Session Type: Concurrent Session

Date: Tuesday, June 4, 2019

Session Time: 2:30pm-4:00pm

Presentation Time: 2:42pm-2:54pm

Location: Ballroom C

*Purpose: The recent recognition of chronic TCMR phenotypes has fostered the need to better evaluate the response of acute TCMR to standard-of-care treatment.

*Methods: Among 2905 consecutive kidney recipients transplanted between 2004-2013, we prospectively included all patients with pure biopsy-proven acute TCMR who received standardized treatment with corticosteroids +/- thymoglobuline. All patients were assessed at the time of diagnosis and 3 months post-treatment for GFR, proteinuria, histology and DSAs, and followed annually up to 2018 to record allograft loss, de novo DSAs and AMR occurrence.

*Results: We included 256 patients diagnosed with acute TCMR at a median time of 4 (IQR, 2-12) months post-transplant. Distribution of TCMR grades was 90 (35%) grade IA, 113 (44%) grade IB, 36 (14%) grade IIA, 10 (4%) grade IIB and 7 (3%) grade III TCMR. Independent post-treatment determinants of allograft loss included: GFR (HR=0.94; 95%CI=0.92-0.96; p<0.001), proteinuria (HR=1.40; 95%CI=1.10-1.79; p=0.007), time since transplantation (HR=1.02; 95%CI=1.00-1.03; p=0.016), peritubular capillaritis (HR=2.27; 95%CI=1.13-4.55; p=0.022), i-IF/TA (HR=1.87; 95%CI=1.08-3.25; p=0.025) and DSAs (HR=2.67; 95%CI=1.46-4.88; p=0.001). Based on a classification tree, we identified 5 profiles of response to treatment (cross-validated accuracy: 0.80). Non-responders included patients with persisting acute TCMR and GFR <22 mL/min (n=28, 10-year graft survival: 12%), patients with i-IF/TA (n=40, 10-year graft survival: 55%) and patients with DSAs (n=33, 10-year graft survival: 57%). Responders included patients without i-IF/TA, without DSAs and with GFR between 22 and 44 mL/min (n=69, 10-year graft survival: 74%) or GFR >44 mL/min (n=86, 10-year graft survival: 93%). Compared with responders (n=155), non-responders (n=101) had a higher incidence of de novo DSAs and AMR at ten years (p<0.001 for both comparisons).

*Conclusions: Clinical, histological and immunological assessment of response to treatment of acute TCMR allowed to uncover different patterns of response to treatment with distinct outcomes, opening avenues for improved treatment and monitoring of patients with acute TCMR.

To cite this abstract in AMA style:

Bouatou Y, Viglietti D, Pievani D, Huyen JDuongVan, Aubert O, Glotz D, Legendre C, Loupy A, Lefaucheur C. Response to Treatment in Kidney Recipients with Acute T Cell-Mediated Rejection: Major Impact of Inflammation in Sclerotic Cortical Parenchyma (i-IF/TA) and Donor-Specific Antibodies [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/response-to-treatment-in-kidney-recipients-with-acute-t-cell-mediated-rejection-major-impact-of-inflammation-in-sclerotic-cortical-parenchyma-i-if-ta-and-donor-specific-antibodies/. Accessed November 22, 2024.

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