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

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

AUTHORS: 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, Meera N Harhay, Sumit Mohan, Thangamani Muthukumar, Bernd Schröppel, Pooja Singh, Francis L Weng, Chirag R Parikh

JOURNAL: Am J Kidney Dis. 2023 Feb;81(2):222-231.e1. doi: 10.1053/j.ajkd.2022.08.011. Epub 2022 Oct 1.

Abstract

Rationale & objective: 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 that manifested in deceased-donor urine biomarkers would be associated with higher rates of biopsy-proven acute rejection (BPAR) and allograft failure after transplantation.

Study design: Prospective cohort.

Setting & participants: 862 deceased donors for 1,137 kidney recipients at 13 centers.

Exposures: We measured concentrations of interleukin 18 (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 (AKIN) criteria to assess donor clinical AKI.

Outcomes: 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 posttransplant year.

Analytical approach: Multivariable Fine-Gray models with death as a competing risk.

Results: Mean recipient age was 54 ± 13 (SD) years, and 82% received antithymocyte globulin. We found no significant associations between donor urinary IL-18, KIM-1, and NGAL and the primary outcome (subdistribution hazard ratio [HR] for highest vs lowest tertile of 0.76 [95% CI, 0.45-1.28], 1.20 [95% CI, 0.69-2.07], and 1.14 [95% CI, 0.71-1.84], respectively). In secondary analyses, we detected no significant associations between clinically defined AKI and the primary outcome or between donor biomarkers and the composite outcome of BPAR, graft failure, and/or de novo DSA.

Limitations: BPAR was ascertained through for-cause biopsies, not surveillance biopsies.

Conclusions: In a large cohort of kidney recipients who almost all received induction with thymoglobulin, donor injury biomarkers were associated with neither graft failure and rejection nor 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.

For the full article, click here.

For a link to the abstract, click here.

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Kelsey Bennett

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