Biomarkers of iron metabolism in chronic kidney disease

Abstract

Iron is the most abundant transition metal in the human body and an essential element required for growth and survival. Our understanding of the molecular control of iron metabolism has increased dramatically over the past 20 years due to the discovery of hepcidin, which regulates the uptake of dietary iron and its mobilization from macrophages and hepatic stores. Anemia and iron deficiency are common in chronic kidney disease. The pathogenesis of anemia of chronic kidney disease is multifactorial. Correction of anemia requires two main treatment strategies: increased stimulation of erythropoiesis, and maintenance of an adequate iron supply to the bone marrow. However, there are still many uncertainties in regard to iron metabolism in patients with chronic kidney disease and in renal replacement therapy. The aim of this review was to summarize the current knowledge on iron metabolism in this population, including new biomarkers of iron status. There is an area of uncertainty regarding diagnostic utility of both erythroferrone (ERFE) and hepcidin in end-stage renal disease (ESRD) patients. Higher concentration of hepcidin in oligoanuric patients may reflect decreased renal clearance. Furthermore, the hepcidin-lowering effect of ERFE in ESRD patients treated with erythropoiesis-stimulating agents (ESAs) may be blunted by underlying inflammation and concomitant iron treatment. Thus, future studies should validate the use of ERFE as a biomarker of erythropoiesis and predictor of response to iron and ESA therapy in dialysis-dependent patients.

Circulating Omentin-1 levels and altered iron balance in chronic haemodialysis patients

“…Importantly, in order to minimize bias, such longitudinal changes were only ascertained in individuals who presented baseline evidence of absolute iron depletion and who maintained evidence of iron correction up to 1 month after the end of the replacement therapy. Of note, this observation parallels similar findings previously reported for other biomarkers [ 27 ], thus indicating that Omentin-1 might represent a potentially useful tool also for the management of iron replacement therapy.…”

Benefits and risks of essential trace elements in chronic kidney disease: a narrative review

“…The disadvantage of traditional threshold values is that they are insensitive to Fe deficiency detection and cannot distinguish absolute and functional Fe deficiency, making it impossible to predict Fe stores and treatment response. In the last two decades, several new biomarkers of Fe status in CKD have been discovered, including the hepcidin-ferroportin axis, erythroferrone, hypoxiainducible factors (HIFs), soluble transferrin receptor, reticulocyte hemoglobin content, and percentage of hypochromic red blood cells (13). However, many of these are influenced by renal failure alone and concomitant inflammation, and because of these confounding effects on the interpretation of most of the biomarkers, the assessment of Fe status in CKD remains a challenge (14).…”

Changes in Iron Availability with Roxadustat in Nondialysis- and Dialysis-Dependent Patients with Anemia of CKD

“…While erythropoiesis is regulated by erythropoietin, the process is also iron-dependent because iron is required for the differentiation of erythroblasts into reticulocytes (4). Iron is absorbed from the gastrointestinal tract and is subsequently bound to serum transferrin for transport to the liver and spleen, where it is bound to ferritin for storage in macrophages and hepatocytes or to the bone marrow for utilization in erythropoiesis (4,5). Some of the processes involved in iron metabolism are regulated by the hormone hepcidin, whose production in the liver is stimulated in response to increased iron availability or inflammation (4).…”