David E Leaf1, Mohan Rajapurkar2, Suhas S Lele3, Banibrata Mukhopadhyay4, Emily A S Boerger5, Finnian R Mc Causland5, Michele F Eisenga6, Karandeep Singh7,8, Jodie L Babitt9, John A Kellum10, Paul M Palevsky11,12, Marta Christov13, Sushrut S Waikar5. 1. Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts; DELEAF@bwh.harvard.edu. 2. Department of Nephrology. 3. Department of Cardiology, and. 4. Department of Biochemistry, Muljibhai Patel Urological Hospital, Gujarat, India. 5. Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 6. Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Departments of. 7. Learning Health Sciences and. 8. Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan. 9. Nephrology Division, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts. 10. Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. 11. Renal Section, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania. 12. Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and. 13. Department of Medicine, New York Medical College, Valhalla, New York.
Abstract
BACKGROUND: Iron is a key mediator of AKI in animal models, but data on circulating iron parameters in human AKI are limited. METHODS: We examined results from the ARF Trial Network study to assess the association of plasma catalytic iron, total iron, transferrin, ferritin, free hemoglobin, and hepcidin with 60-day mortality. Participants included critically ill patients with AKI requiring RRT who were enrolled in the study. RESULTS: Of the 807 study participants, 409 (51%) died by day 60. In both unadjusted and multivariable adjusted models, higher plasma concentrations of catalytic iron were associated with a significantly greater risk of death, as were lower concentrations of hepcidin. After adjusting for other factors, patients with catalytic iron levels in the highest quintile versus the lowest quintile had a 4.06-fold increased risk of death, and patients with hepcidin levels in the lowest quintile versus the highest quintile of hepcidin had a 3.87-fold increased risk of death. These findings were consistent across multiple subgroups. Other iron markers were also associated with death, but the magnitude of the association was greatest for catalytic iron and hepcidin. Higher plasma concentrations of catalytic iron and lower concentrations of hepcidin are each independently associated with mortality in critically ill patients with AKI requiring RRT. CONCLUSIONS: These findings suggest that plasma concentrations of catalytic iron and hepcidin may be useful prognostic markers in patients with AKI. Studies are needed to determine whether strategies to reduce catalytic iron or increase hepcidin might be beneficial in this patient population.
BACKGROUND:Iron is a key mediator of AKI in animal models, but data on circulating iron parameters in human AKI are limited. METHODS: We examined results from the ARF Trial Network study to assess the association of plasma catalytic iron, total iron, transferrin, ferritin, free hemoglobin, and hepcidin with 60-day mortality. Participants included critically illpatients with AKI requiring RRT who were enrolled in the study. RESULTS: Of the 807 study participants, 409 (51%) died by day 60. In both unadjusted and multivariable adjusted models, higher plasma concentrations of catalytic iron were associated with a significantly greater risk of death, as were lower concentrations of hepcidin. After adjusting for other factors, patients with catalytic iron levels in the highest quintile versus the lowest quintile had a 4.06-fold increased risk of death, and patients with hepcidin levels in the lowest quintile versus the highest quintile of hepcidin had a 3.87-fold increased risk of death. These findings were consistent across multiple subgroups. Other iron markers were also associated with death, but the magnitude of the association was greatest for catalytic iron and hepcidin. Higher plasma concentrations of catalytic iron and lower concentrations of hepcidin are each independently associated with mortality in critically illpatients with AKI requiring RRT. CONCLUSIONS: These findings suggest that plasma concentrations of catalytic iron and hepcidin may be useful prognostic markers in patients with AKI. Studies are needed to determine whether strategies to reduce catalytic iron or increase hepcidin might be beneficial in this patient population.
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