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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)222-231.e1
JournalAmerican Journal of Kidney Diseases
Issue number2
StatePublished - Feb 2023


  • Kidney transplantation
  • acute kidney injury (AKI)
  • biomarkers
  • biopsy-proven acute rejection (BPAR)
  • de novo DSA
  • deceased organ donation
  • donor-specific antibody (DSA)
  • graft failure
  • inflammation
  • injury hypothesis
  • organ acceptance

ASJC Scopus subject areas

  • Nephrology


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