Deferasirox treatment may be associated with reversible renal Fanconi syndrome

Even‐Or, Ehud; Becker-Cohen, Rachel; Miskin, Hagit

doi:10.1002/ajh.21588

Cited by 26 publications

(38 citation statements)

References 9 publications

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“…Deferasirox-associated Fanconi syndrome has been reported to develop within a mean of 17.8 months (range 1-36 months) following initiation of therapy and to be reversible within a mean of 3 weeks (range of 3 days to 6 weeks) following its discontinuation. 27,31,[34][35][36][37][38][39][40] Most reports indicated an absence of features of Fanconi syndrome before prescription of deferasirox. 27,31,35,[37][38][39][40] However, in two reports, baseline values were not presented.…”

Section: Proximal Tubular Injury and Fanconi Syndromementioning

confidence: 97%

Deferasirox nephrotoxicity—the knowns and unknowns

et al. 2014

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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.

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Section: Proximal Tubular Injury and Fanconi Syndromementioning

confidence: 97%

Deferasirox nephrotoxicity—the knowns and unknowns

et al. 2014

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“…Renal tubular dysfunction including generalized aminoaciduria, protein urine, and glycosuria also reversed after deferasirox was stopped. (2) In this case, reintroduction of low-dose deferasirox was possible without further compromising BMD. This case illustrates the dramatic effect of chronic hypophosphataemia secondary to renal phosphate loss on the skeleton and demonstrates the potential for renal tubular toxicity of deferasirox despite normal serum creatinine levels.…”

Section: Discussionmentioning

confidence: 78%

“…(13) However, more serious renal dysfunction had been associated with deferasirox use including biopsy proven acute interstitial nephritis. (14) More recently, reports of acquired Fanconi's syndrome have been reported with the use of deferasirox (1)(2)(3)(4) with recurrence after cessation and rechallenge. (2) The administration of parenteral iron has been shown to suppress renal phosphate reabsorption resulting in hypophosphatemia through increased levels of FGF-23.…”

Section: Discussionmentioning

confidence: 99%

“…(14) More recently, reports of acquired Fanconi's syndrome have been reported with the use of deferasirox (1)(2)(3)(4) with recurrence after cessation and rechallenge. (2) The administration of parenteral iron has been shown to suppress renal phosphate reabsorption resulting in hypophosphatemia through increased levels of FGF-23. (15) The presence of normal FGF-23 levels, hypophosphatemia, and reduced tubular phosphate reabsorption in this case, suggests that FGF-23 is not the major cause of renal phosphate wasting.…”

Section: Discussionmentioning

confidence: 99%

“…The availability of deferasirox (Exjade 1 ), an orally active iron chelator, over the past 4 years represented a necessary alternative for patients requiring chelation therapy. However, there have been increasing reports of proximal renal tubular dysfunction and Fanconi Syndrome (1)(2)(3)(4) associated with deferasirox in the literature. We report a case of hypophosphatemic osteomalacia secondary to deferasirox therapy.…”

Section: Introductionmentioning

confidence: 99%

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A case of hypophosphatemic osteomalacia secondary to deferasirox therapy

Milat

Wong

Fuller

et al. 2011

Journal of Bone and Mineral Research

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Patients with b-thalassemia major require iron-chelation therapy to avoid the complication of iron overload. Until recently, deferoxamine (DFO) was the major iron chelator used in patients requiring chronic hypertransfusion therapy, but DFO required continuous subcutaneous therapy. The availability of deferasirox (Exjade 1 ), an orally active iron chelator, over the past 4 years represented a necessary alternative for patients requiring chelation therapy. However, there have been increasing reports of proximal renal tubular dysfunction and Fanconi Syndrome associated with deferasirox in the literature. We report a case of hypophosphataemic osteomalacia secondary to deferasirox therapy. ß

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Thalassemia Bone Disease: A 19-Year Longitudinal Analysis

Wong

Fuller

Gillespie

et al. 2014

Journal of Bone and Mineral Research

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Thalassemia is an inherited disorder of alpha or beta globin chain synthesis leading to ineffective erythropoiesis requiring chronic transfusion therapy in its most severe form. This leads to iron overload, marrow expansion, and hormonal complications, which are implicated in bone deformity and loss of bone mineral density (BMD). In this 19-year retrospective longitudinal study, the relationships between BMD (determined by dual-energy X-ray absorptiometry) and risk factors for osteoporosis in 277 subjects with transfusiondependent thalassemia were examined. The mean age at first review was 23.2 AE 11.9 years and 43.7% were male. Hypogonadism was present in 28.9%. Fractures were confirmed in 11.6% of subjects and were more frequent in males (16.5%) compared with females (7.7%). Lumbar spine (LS), femoral neck (FN), and total body (TB) Z-scores were derived. Patients with transfusion-dependent thalassemia had a significant longitudinal decline in BMD at the FN and TB. In the linear mixed-model analysis of BMD and risk factors for bone loss, FN Z-score was more significantly associated with risk factors compared with the LS and TB. The rate of decline at the FN was 0.02 Z-score per year and was 3.85-fold greater in males. The decline in FN Z-score over the last 5 years (years 15 to 19) was 2.5-fold that of the previous 7 years (years 8 to 14) and coincided with a change in iron chelator therapy from desferrioxamine to deferasirox. Hemoglobin (Hb) levels positively correlated with higher TB and LS Z-scores. In conclusion, the FN is the preferred site for follow-up of BMD. Male patients with b-thalassemia experienced a greater loss of BMD and had a higher prevalence of fractures compared with females. Transfusing patients (particularly males) to a higher Hb target may reduce the decline in BMD. Whether deferasirox is implicated in bone loss warrants further study.

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Deferasirox treatment may be associated with reversible renal Fanconi syndrome

Cited by 26 publications

References 9 publications

Deferasirox nephrotoxicity—the knowns and unknowns

Deferasirox nephrotoxicity—the knowns and unknowns

A case of hypophosphatemic osteomalacia secondary to deferasirox therapy

Thalassemia Bone Disease: A 19-Year Longitudinal Analysis

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