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Transpl Int. 2019 May;32(5):502-515. doi: 10.1111/tri.13395. Epub 2019 Feb 8.

Factors at de novo donor-specific antibody initial detection associated with allograft loss: a multicenter study.

Author information

1
William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN, USA.
2
Department of Transplantation Medicine, New-York Presbyterian Hospital Weill NYP-WCM Medical College, New York, NY, USA.
3
Terasaki Research Institute, Los Angeles, CA, USA.
4
Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
5
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
6
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
7
Henry Ford Transplant Institute, Detroit, MI, USA.

Abstract

We aimed to evaluate patient factors including nonadherence and viral infection and de novo donor-specific antibody (dnDSA) characteristics [total immunoglobulin G (IgG), C1q, IgG3, and IgG4] as predictors of renal allograft failure in a multicenter cohort with dnDSA. We performed a retrospective observational study of 113 kidney transplant recipients with dnDSA and stored sera for analysis. Predictors of death-censored allograft loss were assessed by Cox proportional modeling. Death-censored allograft survival was 77.0% (87/113) during a median follow-up of 2.2 (IQR 1.2-3.7) years after dnDSA detection. Predictors of allograft failure included medication nonadherence [HR 6.5 (95% CI 2.6-15.9)], prior viral infection requiring immunosuppression reduction [HR 5.3 (95% CI 2.1-13.5)], IgG3 positivity [HR 3.8 (95% CI 1.5, 9.3)], and time post-transplant (years) until donor-specific antibody (DSA) detection [HR 1.2 (95% CI 1.0, 1.3)]. In the 67 patients who were biopsied at dnDSA detection, chronic antibody-mediated rejection [HR 11.4 (95% CI 2.3, 56.0)] and mixed rejection [HR 7.4 (95% CI 2.2, 24.8)] were associated with allograft failure. We conclude that patient factors, including a history of viral infection requiring immunosuppression reduction or medication nonadherence, combined with DSA and histologic parameters must be considered to understand the risk of allograft failure in patients with dnDSA.

KEYWORDS:

HLA-antibody post-transplantation; histocompatibility and immunogenetics; infection; kidney clinical; other; rejection

PMID:
30597643
PMCID:
PMC6483899
[Available on 2020-05-01]
DOI:
10.1111/tri.13395

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