title: Deferasirox at therapeutic doses is associated with dose-dependent hypercalciuria.
abstract: Deferasirox is an oral iron chelator used widely in the treatment of thalassemia major and other transfusion-dependent hemoglobinopathies. Whilst initial long-term studies established the renal safety of deferasirox, there are now increasing reports of hypercalciuria and renal tubular dysfunction. In addition, urolithiasis with rapid loss of bone density in patients with β thalassemia major has been reported. We conducted a cross-sectional cohort study enrolling 152 adult patients comprising of β thalassemia major (81.5%), sickle cell disease (8%), thalassemia intermedia (2%), HbH disease (6.5%) and E/β thalassemia (2%). Cases were matched with normal control subjects on age, gender and serum creatinine. Iron chelator use was documented and urine calcium to creatinine ratios measured. At the time of analysis, 88.8% of patients were receiving deferasirox and 11.2% were on deferoxamine. Hypercalciuria was present in 91.9% of subjects on deferasirox in a positive dose-dependent relationship. This was not seen with subjects receiving deferoxamine. At a mean dose of 30.2±8.8mg/kg/day, deferasirox was associated with an almost 4 fold increase in urine calcium to creatinine ratio (UCa/Cr). Hypercalciuria was present at therapeutic doses of deferasirox in a dose-dependent manner and warrants further investigation and vigilance for osteoporosis, urolithiasis and other markers of renal dysfunction.
authors.affiliation: Hudson Institute of Medical Research, Victoria, Australia; Department of Endocrinology, Monash Health, Victoria, Australia; Department of Medicine, Monash University, Victoria, Australia. Electronic address: phillip.wong@hudson.org.au.
authors.forename: Phillip
authors.initials: P
authors.lastname: Wong
authors.affiliation: Department of Medicine, Monash University, Victoria, Australia; Department of Nephrology, Monash Health, Victoria, Australia.
authors.forename: Kevan
authors.initials: K
authors.lastname: Polkinghorne
authors.affiliation: Department of Medicine, Monash University, Victoria, Australia; Department of Nephrology, Monash Health, Victoria, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kerr
authors.affiliation: Department of Medicine, Monash University, Victoria, Australia; Department of Pathology, Monash Health, Victoria, Australia.
authors.forename: James C G
authors.initials: JC
authors.lastname: Doery
authors.affiliation: Hudson Institute of Medical Research, Victoria, Australia; Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Gillespie
authors.affiliation: Department of Pharmacy, Monash Health, Victoria, Australia.
authors.forename: I
authors.initials: I
authors.lastname: Larmour
authors.affiliation: Hudson Institute of Medical Research, Victoria, Australia; Department of Endocrinology, Monash Health, Victoria, Australia; Department of Medicine, Monash University, Victoria, Australia; Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Fuller
authors.affiliation: Thalassemia Service, Monash Health, Victoria, Australia.
authors.forename: Donald K
authors.initials: DK
authors.lastname: Bowden
authors.affiliation: Hudson Institute of Medical Research, Victoria, Australia; Department of Endocrinology, Monash Health, Victoria, Australia; Department of Medicine, Monash University, Victoria, Australia.
authors.forename: Frances
authors.initials: F
authors.lastname: Milat
mesh_terms: D000328:Adult; D001565:Benzoates / Q000009:adverse effects* / Q000627:therapeutic use*; D002118:Calcium / Q000652:urine; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine; D000077588:Deferasirox; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D053565:Hypercalciuria / Q000139:chemically induced* / Q000652:urine; D008297:Male; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D001565:Benzoates; D014230:Triazoles; D003404:Creatinine; D002118:Calcium; D000077588:Deferasirox
keywords: Deferasirox; Disorders of calcium; Hypercalciuria; Iron overload; Thalassemia