TY - JOUR
T1 - Deceased-Donor Acute Kidney Injury and Acute Rejection in Kidney Transplant Recipients
T2 - A Multicenter Cohort
AU - Reese, Peter P.
AU - Doshi, Mona D.
AU - Hall, Isaac E.
AU - Besharatian, Behdad
AU - Bromberg, Jonathan S.
AU - Thiessen-Philbrook, Heather
AU - Jia, Yaqi
AU - Kamoun, Malek
AU - Mansour, Sherry G.
AU - Akalin, Enver
AU - Harhay, Meera N.
AU - Mohan, Sumit
AU - Muthukumar, Thangamani
AU - Schröppel, Bernd
AU - Singh, Pooja
AU - Weng, Francis L.
AU - Parikh, Chirag R.
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2023/2
Y1 - 2023/2
N2 - 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.
AB - 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.
KW - Kidney transplantation
KW - acute kidney injury (AKI)
KW - biomarkers
KW - biopsy-proven acute rejection (BPAR)
KW - de novo DSA
KW - deceased organ donation
KW - donor-specific antibody (DSA)
KW - graft failure
KW - inflammation
KW - injury hypothesis
KW - organ acceptance
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U2 - 10.1053/j.ajkd.2022.08.011
DO - 10.1053/j.ajkd.2022.08.011
M3 - Article
C2 - 36191727
AN - SCOPUS:85144506125
SN - 0272-6386
VL - 81
SP - 222-231.e1
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 2
ER -