Work

Iron, Hepcidin, and Death in Human AKI

Year: 2019

Type: article

Abstract: Significance Statement Dysregulated iron metabolism plays an important pathogenic role in AKI in animal models, but limited data are available on circulating iron parameters in human AKI. To assess the association of plasma catalytic iron, total iron, transferrin, TSAT, ferritin, free hemoglobin, and hepcidin with 60-day mortality, the authors examined observations in a cohort study of 807 critically ill patients with AKI (all requiring RRT) who were enrolled the ARF Trial Network study. They found that higher concentrations of catalytic iron and lower concentrations of hepcidin are each monotonically and independently associated with increased mortality. These findings identify plasma catalytic iron and hepcidin as potentially useful prognostic markers or therapeutic targets in patients with AKI requiring RRT. 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.

Source: Journal of the American Society of Nephrology

DOI: 10.1681/asn.2018100979