EVALUATION OF IRON METABOLISM DISORDERS AND THEIR RELATIONSHIP WITH CHRONIC ANEMIA IN ADULT POPULATIONS

Abstract

The iron metabolism disorders form a range of human diseases between iron deficiency anemia and iron overload with the hepcidin-ferroportin axis as the key regulatory system of systemic iron homeostasis. As a way of assessing the disorder, the paper presents a systematic review and quantitative synthesis of iron metabolism disorders in adult populations, which summarizes information offered by 4,287 patients with absolute iron deficiency, functional iron deficiency, iron overload, and healthy control. Mathematical modeling of hepidin-ferroportin kinetics revealed a Hill coefficient of 2.4 and an IC 0 of 8.2 nM that indicated cooperative inhibition of iron efflux by ferroportin. Pathologic biomarker phenotype of functional iron deficiency was a high hepcidin (median 48.7 ng/mL), inappropriately high ferritin (312.5 plus 98.4 µg/L) despite low saturation of transferrin (14.5 plus 5.2%), and considerably high interleukin-6 (12.5 Kinetic A combination diagnostic algorithm that included hepcidin, ferritin, transferrin saturation and soluble transferrin receptor displayed a discriminative ability of absolute iron deficiency as compared with functional iron deficiency (AUC = 0.96, 95% CI 0.94-0.98) that was significantly greater than single biomarkers. The three-dimensional predictive surface modeling gave a predictive region that is highly predictive of functional iron deficiency (probability > 0.9); hepcidin is above 30 ng/mL and ferritin is between 100 and 300 µg/L. The findings conclude that the hepcidinferroportin axis is the most important determinant of the iron status in chronic anemia and that a composite biomarker approach can be employed to precisely differentiate between the iron disease when classic markers are confounded by inflammation. This model provides a mechanistic foundation to the diagnostic and treatment plans based on accuracy in iron-related diseases.