Iron metabolism and management: focus on chronic kidney disease

Abstract

Anemia is common in patients with chronic kidney disease (CKD) and results from the dysregulation of iron metabolism and erythropoiesis. Hepcidin is a key regulator of iron availability and leads to iron sequestration during the state of iron repletion. Decreases in the level of hepcidin in the presence of hypoxia and/or iron limitation allow for greater iron availability for erythropoiesis. However, kidney excretion of hepcidin decreases as the severity of CKD increases, whereas production of hepcidin is increased under inflammatory conditions often present in patients with CKD, both of which contribute to anemia. Assessment of iron status is, therefore, essential in the treatment of anemia. However, current laboratory tests for the determination of the adequate supply of iron have many limitations, including diurnal variation in the levels of biomarkers, lack of standardized reference methods across laboratories, and confounding by the presence of inflammation. In addition, the current treatment paradigm for anemia of CKD can further disrupt iron homeostasis; for example, treatment with erythropoiesis-stimulating agents in the absence of supplemental iron can induce functional iron deficiency. Moreover, supplemental iron can further increase levels of hepcidin. Several novel therapies, including hypoxia-inducible factor prolyl hydroxylase inhibitors and hepcidin inhibitors/antagonists, have shown promise in attenuating the levels and/or activity of hepcidin in anemia of CKD, thus ensuring the availability of iron for erythropoiesis.

Serum hepcidin levels as indicator of anemia status in male hemodialysis patients

“…The results showed that HD patients have a high significant (p=0.0001) increase in mean of serum Hepcidin level of (622.3±139.6) pg/ml, as compared with the controls group about (465.16±80.31) pg/ml, Figure (1). Furthermore, hepcidin levels exhibited a significant (p< 0.05) increase in 37% of HD patients with severe anemia about (692.4±119.8) pg/ml more than patient with 49.2% of moderate about (605.3±117.7) pg/ml, (p=0.007) as compared with 13.8% of mild anemia groups (531.8±99.12) pg/ml, (p=0.001), but no significant between mild and moderate anemia groups (p=0.099), Figure (2).…”

“…The statistical analysis in the Table (1) indicated to 90 samples consisted of 65 HD patients with median (IQR) dialysis vintage was (12 (3-36) month, compared with 25 healthy participates as control group. No significant differences in the mean ages of the HD patients were (45.65±13.34) compared to control groups were (50±12.73) year, (p=0.164).…”

“…Hepcidin expression is stimulated by iron overload, inflammation, and erythropoietic activity (Nemeth et al;. Instead of conventional iron indices, Hepcidin, may have been a superior biomarker of anemia in HD patients because it is more fundamental; It reduces accessible blood iron levels by reducing iron export from whole-body iron storage , Agarwal, 2021. Few studies have examined at the varied relationships between hepcidin and iron indices with anemia severity depending on the anemia and kidney function.…”

Treatment of Anemia in Kidney Disease: Beyond Erythropoietin

“…Hepcidin, a peptide produced in the liver, was discovered in 2000 and is the key regulator of iron use, recycling, and transport. 19 , 20 , 21 Its physiologic role is to protect the organism against iron overload and to sequester iron in storage sites in the presence of infection by siderophilic pathogens. Hepcidin synthesis is stimulated by inflammation and increased storage iron and is decreased by iron deficiency and erythropoiesis.…”

Vitamin D supplementation on anemia markers and the impact on PTH in patients with chronic kidney disease

“…The main causes of anemia are: reduced production of erythropoietin (EPO), which stimulates the production of erythrocytes (Bueno & Frizzo, 2014;Naini et al, 2015;Oliveira et al, 2019;Agarwal, 2021), deficiency of iron, inflammation, and vitamin D axis deficiencies (Zughaier et al, 2014;Bacchetta et al, 2014;Lima, 2017;Al-shaer et al, 2020).…”