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

Rationale & Objective: Donor acute kidney injury (AKI) activates innate immunity, enhances HLA expression in the kidney allo-graft, and provokes recipient alloimmune re-sponses. 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 com-posite of BPAR and graft failure (not from death). A secondary outcome was the com-posite 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 thymoglo-bulin, donor injury biomarkers were associated with neither graft failure and rejection nor a secondary outcome that included de novo DSA. These find-ings provide some reassurance that centers can successfully manage immunological complications using deceased-donor kidneys with AKI.