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Deceased-Donor Acute Kidney Injury and Acute Rejection in Kidney Transplant Recipients: A Multicenter Cohort
Journal article   Open access   Peer reviewed

Deceased-Donor Acute Kidney Injury and Acute Rejection in Kidney Transplant Recipients: A Multicenter Cohort

Peter P. Reese, Mona D. Doshi, Isaac E. Hall, Behdad Besharatian, Jonathan S. Bromberg, Heather Thiessen-Philbrook, Yaqi Jia, Malek Kamoun, Sherry G. Mansour, Enver Akalin, …
American journal of kidney diseases
30 Sep 2022
url
http://www.ajkd.org/article/S0272638622009209/pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1053/j.ajkd.2022.08.011View
Published, Version of Record (VoR) Open

Abstract

Acute kidney injury Biomarkers Deceased organ donation Graft failure Kidney transplantation
Donor acute kidney injury (AKI) activates innate immunity, enhances HLA expression in the kidney allograft, and provokes recipient alloimmune responses. We hypothesized that injury and inflammation manifested in deceased-donor urine biomarkers would be associated with higher rates of biopsy-proven acute rejection (BPAR) and allograft failure after transplantation. Prospective cohort. 862 deceased donors for 1137 kidney recipients at 13 centers. We measured concentrations of IL-18, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) in deceased donor urine. We also used the Acute Kidney Injury Network criteria to assess donor clinical AKI. The primary outcome was a composite of BPAR and graft failure (not from death). A secondary outcome was the composite of BPAR, graft failure, and/or de novo donor specific antibody (DSA). Outcomes were ascertained in the first post-transplant year. Multivariable Fine-Gray models with death as a competing risk. Mean recipient age was 54±13 years and 82% received anti-thymocyte globulin. We found no significant associations between donor urinary IL-18 (subdistribution hazard ratio [sHR] for highest vs. lowest tertile 0.76; 95% CI 0.45, 1.28), KIM-1 (sHR 1.2; 95% CI 0.69, 2.07) or NGAL (sHR 1.14; 95% CI 0.71, 1.84) and the primary outcome. In secondary analyses, we detected no significant associations between a) clinically-defined AKI and the primary outcome, or between b) donor biomarkers and the composite outcome of BPAR, graft failure and/or de novo DSA. BPAR ascertained through for-cause biopsies, not surveillance biopsies. In a large cohort of kidney recipients that were almost all induced with thymoglobulin, donor injury biomarkers were neither associated with graft failure and rejection, nor with a secondary outcome that included de novo DSA. These findings provide some reassurance that centers can successfully manage immunological complications using deceased-donor kidneys with AKI. [Display omitted]

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Urology & Nephrology
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