title: Iron metabolism in the pathogenesis of iron-induced kidney injury.
abstract: In the past 8 years, there has been renewed interest in the role of iron in both acute kidney injury (AKI) and chronic kidney disease (CKD). In patients with kidney diseases, renal tubules are exposed to a high concentration of iron owing to increased glomerular filtration of iron and iron-containing proteins, including haemoglobin, transferrin and neutrophil gelatinase-associated lipocalin (NGAL). Levels of intracellular catalytic iron may increase when glomerular and renal tubular cells are injured. Reducing the excessive luminal or intracellular levels of iron in the kidney could be a promising approach to treat AKI and CKD. Understanding the role of iron in kidney injury and as a therapeutic target requires insight into the mechanisms of iron metabolism in the kidney, the role of endogenous proteins involved in iron chelation and transport, including hepcidin, NGAL, the NGAL receptor and divalent metal transporter 1, and iron-induced toxic effects. This Review summarizes emerging knowledge, which suggests that complex mechanisms of iron metabolism exist in the kidney, modulated directly or indirectly by cellular iron content, inflammation, ischaemia and oxidative stress. The potential exists for prevention and treatment of iron-induced kidney injury by customized iron removal or relocation, aided by detailed insight into the underlying pathological mechanisms.
authors.affiliation: Department of Laboratory Medicine, Laboratory of Genetic Endocrine and Metabolic diseases, Radboud University Medical Centre, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, the Netherlands.
authors.forename: A M F
authors.initials: AM
authors.lastname: Martines
authors.forename: R
authors.initials: R
authors.lastname: Masereeuw
authors.forename: H
authors.initials: H
authors.lastname: Tjalsma
authors.forename: J G
authors.initials: JG
authors.lastname: Hoenderop
authors.forename: J F M
authors.initials: JF
authors.lastname: Wetzels
authors.forename: D W
authors.initials: DW
authors.lastname: Swinkels
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000150:complications* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000378:metabolism
chemical_list: D007501:Iron