According to the results of study published in Blood, inflammation overrides erythropoietic signals in determining hepcidin concentration in patients with tuberculosis, and these patients also have negligible iron absorption, contributing to anemia of inflammation—a hallmark of tuberculosis.
The investigators conducted a 26-week prospective study in eastern Tanzania between April 2015 and January 2017 to describe iron kinetics and changes in inflammation and iron metabolism indices during recovery from anemia of inflammation and to inform clinical practice on whether patients should be given iron supplementation during tuberculosis treatment.
To determine iron absorption and utilization, patients with tuberculosis (with body weight >40 kg and hemoglobin [Hb] >70 g/L) received oral and intravenous iron tracers before, during (at 8 and 12 weeks), and after treatment (24 weeks) and were evaluated in follow up visits every 2 weeks during the study.
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A total of 19 adult patients with tuberculosis (3 female, 16 male) participated in the study. Their mean age was 31.1 years (range, 18-45). After 7 weeks, 1 male patient withdrew due to lack of interest.
Before treatment, all participants had inflammation indicated by elevated α1-acidglycoprotein, C-reactive protein, and interleukin (IL)-6, and 11 patients (61%) had anemia of inflammation. Hepcidin (geometric mean, 21.4 nM), erythroferrone (130.1 pg/mL), and erythrocyte iron use (approximately 80%) were greatly elevated, whereas iron absorption was minimal (<1%).
During treatment, hepcidin and IL-6 levels decreased rapidly—by approximately 70% each—after 2 weeks (P <.001), and inflammation further resolved during treatment. The decrease in erythroferrone became significant at 8 weeks (P <.05).
In regression models, hepcidin was negatively associated erythroferrone (P <.05), while it was positively associated with IL-6 (P <.02). Increased erythroferrone was also associated with reticulocytosis and Hb repletion (P <.01).
During intensive phase treatment, dilution of the baseline tracer concentration was increased by 2.6-fold relative to baseline (P <.01), indicating enhanced erythropoiesis. After treatment completion, iron absorption increased by approximately 20-fold (P <.001) and Hb increased by approximately 25%, compared with baseline levels (11.1 vs 13.9 g/dL; P <.001).
The data provide evidence for guidelines on iron treatment of tuberculosis-associated anemia. “Our results suggest that iron supplementation before and during treatment of tuberculosis is likely to be ineffective, and, at least in our patients, unnecessary, as mobilization of sequestered iron provided ample iron for erythropoiesis and Hb recovery, as in previous studies,” the authors wrote. “Our data suggest that iron supplementation should only be given to tuberculosis patients who remain anemic after completion of treatment.”
The team did not evaluate the efficacy of iron supplementation in these patients. They called for additional clinical trials to determine the risks, benefits, and optimal timing of iron supplementation in patients with tuberculosis, both those with anemia of inflammation and those with iron-deficiency anemia.
Reference
Cercamondi CI, Stoffel NU, Moretti D, et al. Iron homeostasis during anemia of inflammation: a prospective study of patients with tuberculosis. Blood. 2021;138(15):1293-1303. doi:10.1182/blood.2020010562
