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

Publication/Presentation Date

2-1-2023

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.

Volume

81

Issue

2

First Page

222

Last Page

231

ISSN

1523-6838

Published In/Presented At

Reese, P. P., Doshi, M. D., Hall, I. E., Besharatian, B., Bromberg, J. S., Thiessen-Philbrook, H., Jia, Y., Kamoun, M., Mansour, S. G., Akalin, E., Harhay, M. N., Mohan, S., Muthukumar, T., Schröppel, B., Singh, P., Weng, F. L., & Parikh, C. R. (2023). Deceased-Donor Acute Kidney Injury and Acute Rejection in Kidney Transplant Recipients: A Multicenter Cohort. American journal of kidney diseases : the official journal of the National Kidney Foundation, 81(2), 222–231.e1. https://doi.org/10.1053/j.ajkd.2022.08.011

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

36191727

Department(s)

Administration and Leadership

Document Type

Article