Acquired Proximal Renal Tubular Dysfunction in β-Thalassemia Patients Treated With Deferasirox

Abstract

Deferasirox is a recently approved oral iron chelator for treatment of patients with transfusion-related iron overload. Although renal function disturbances were recognized, proximal renal tubulopathy was not addressed in published safety reports for deferasirox. Although subclinical proximal tubulopathy was described in β-thalassemia homozygotes, overt Fanconi kidney is not an established disease complication. We describe 4 cases out of 50 children and adults with transfusion-dependent β-thalassemia, treated with deferasirox for iron overload, who developed clinically significant Fanconi syndrome. Three had concomitant infectious events; the fourth case was entirely spontaneous. In addition, all 4 patients were moderately to well chelated. Cessation of deferasirox resulted in prompt recovery. We propose the necessity for diligent monitoring for proximal tubule nephropathy, possibly related to infectious events, during treatment with deferasirox.

Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up

“…No progressive increases in serum creatinine or liver transaminase levels were observed during long-term deferasirox treatment, and creatinine clearance remained stable. Fanconi-like syndrome in the kidney during deferasirox treatment has been reported rarely [32][33][34] but was not observed in this study. Patients with 2 consecutive increases in serum creatinine Ͼ 33% above the start of deferasirox and Ͼ ULN were most frequently in higher average actual dose categories, but such increases were manageable and did not lead to permanent discontinuation of deferasirox.…”

Deferasirox nephrotoxicity—the knowns and unknowns

“…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.…”

“…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. 34,36 Fanconi syndrome related to deferasirox use has most commonly been reported to occur in very young (aged ≤16 years) and elderly patients (aged ≥65 years; Table 3).…”

A case of hypophosphatemic osteomalacia secondary to deferasirox therapy

“…(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.…”

“…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.…”