title: Deferasirox nephrotoxicity-the knowns and unknowns.
abstract: In 2005, the oral iron chelator deferasirox was approved by the FDA for clinical use as a first-line therapy for blood-transfusion-related iron overload. Nephrotoxicity is the most serious and frequent adverse effect of deferasirox treatment. This nephrotoxicity can present as an acute or chronic decrease in glomerular filtration rate (GFR). Features of proximal tubular dysfunction might also be present. In clinical trials and observational studies, GFR is decreased in 30-100% of patients treated with deferasirox, depending on dose, method of assessment and population studied. Nephrotoxicity is usually nonprogressive and/or reversible and rapid iron depletion is one of several risk factors. Scarce data are available on the molecular mechanisms of nephrotoxicity and the reasons for the specific proximal tubular sensitivity to the drug. Although deferasirox promotes apoptosis of cultured proximal tubular cells, the trigger has not been well characterized. Observational studies are required to track current trends in deferasirox prescription, assess the epidemiology of deferasirox nephrotoxicity in routine clinical practice, explore the effect on outcomes of various monitoring and dose-adjustment protocols and elucidate the long-term consequences of the different features of nephrotoxicity. Deferasirox nephrotoxicity can be more common in the elderly; thus, specific efforts should be dedicated to investigate the effect of deferasirox use in this group of patients.
authors.affiliation: Escuela Superior de Medicina del Instituto Politécnico Nacional, Avenida Salvador Díaz Mirón s/n, 11340 Ciudad de México, México.
authors.forename: Juan Daniel
authors.initials: JD
authors.lastname: Díaz-García
authors.affiliation: IIS-Fundación Jiménez Díaz-UAM, Avenida Reyes Católicos 2, 28040 Madrid, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Gallegos-Villalobos
authors.affiliation: IIS-Fundación Jiménez Díaz-UAM, Avenida Reyes Católicos 2, 28040 Madrid, Spain.
authors.forename: Liliana
authors.initials: L
authors.lastname: Gonzalez-Espinoza
authors.affiliation: IDIPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Sanchez-Niño
authors.affiliation: Hospital Ramon y Cajal, Carretera de Colmenar Viejo km. 9,100, 28034 Madrid, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Villarrubia
authors.affiliation: Unidad de Diálisis, Fundación Jiménez Díaz-IRSIN, Avenida Reyes Católicos 2, 28040 Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D001565:Benzoates / Q000009:adverse effects*; D000077588:Deferasirox; D005919:Glomerular Filtration Rate; D006801:Humans; D007502:Iron Chelating Agents / Q000009:adverse effects*; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced*; D065227:Transfusion Reaction; D014230:Triazoles / Q000009:adverse effects*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox