Iron, Hepcidin, and Death in Human AKI

• Published in: Journal of the American Society of Nephrology Vol. 30; no. 3; pp. 493 - 504
• Main Authors: Leaf, David E, Rajapurkar, Mohan, Lele, Suhas S, Mukhopadhyay, Banibrata, Boerger, Emily A S, Mc Causland, Finnian R, Eisenga, Michele F, Singh, Karandeep, Babitt, Jodie L, Kellum, John A, Palevsky, Paul M, Christov, Marta, Waikar, Sushrut S
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.03.2019
• Subjects: Acute Kidney Injury - blood; Acute Kidney Injury - mortality; Acute Kidney Injury - therapy; Aged; Biomarkers - blood; Clinical Research; Cohort Studies; Female; Ferritins - blood; Hemoglobins - metabolism; Hepcidins - blood; Humans; Iron - blood; Male; Middle Aged; Prognosis; Randomized Controlled Trials as Topic; Renal Replacement Therapy; Risk Factors; Transferrin - metabolism; United States - epidemiology; United States; acute renal failure; nephrotoxicity; outcomes; mortality risk
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2018100979

Iron is a key mediator of AKI in animal models, but data on circulating iron parameters in human AKI are limited. 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. 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. 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.