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Deferasirox-induced renal impairment in children: an increasing concern for pediatricians

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Abstract

Background

Deferasirox (DFX) is an oral iron chelator with an established dose-dependent efficacy in transfusion-related iron overload. Whereas emerging long-term data confirm the safety of the drug, with transient moderate elevation of serum creatinine level, several authors have reported renal tubular dysfunction. The aim of this study was to evaluate tubular and glomerular function before and after the initiation of DFX therapy in a pediatric patient population.

Methods

Ten children (4 girls, mean age 12.4 ± 3.9 years) enrolled in a routine blood transfusion program were treated with 24.8 ± 9.6 mg/kg per day of DFX, and renal function was assessed before and 17.2 ± 8.9 months after the initiation of DFX therapy.

Results

Prior to treatment with DFX, all patients had a normal glomerular function rate (GFR) (125 ± 15 ml/min per 1.73 m2) and normal tubular function. Following the initiation of DFX therapy, the GFR decreased by approximately 20 % with one patient with a GFR of <80 mL/min per 1.73 m2 and seven patients with a GFR of <100 mL/min per 1.73 m2. Two patients experienced a generalized proximal tubular dysfunction whereas nine patients presented at least one sign of proximal tubular dysfunction.

Conclusions

Renal toxicity is a frequent adverse event of DFX treatment, presenting as both glomerular and proximal dysfunction. A routine renal assessment is therefore required to prevent chronic kidney disease that may result from prolonged tubular injury.

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Abbreviations

DFX:

Deferasirox

eGFR:

Estimated glomerular filtration rate

FEUA:

Fractional excretion of uric acid

GFR:

Glomerular filtration rate

iGFR:

True glomerular filtration rate (inulin clearance)

Pcr:

Plasma creatinine

PO4 :

Plasma phosphate

TmP/GFR:

Tubular maximal phosphate reabsorption corrected by GFR

UA:

Plasma Uric acid

Ualb/Ucr:

Urinary albumin to creatinine ratio

Ualb:

Albuminuria

UCa/Ucr:

Urinary calcium to creatinine ratio

UMg/Ucr:

Urinary magnesium to creatinine ratio

β2 M:

Urinary β2-microglobulin level

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Authors and Affiliations

  1. Centre de Référence des Maladies Rénales Rares, Service de Néphrologie et Rhumatologie Pédiatriques, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France

    Laurence Dubourg, Céline Laurain, Bruno Ranchin & Pierre Cochat

  2. Exploration Fonctionnelle Rénale et Métabolique, Hospices Civils de Lyon, Lyon, France

    Laurence Dubourg & Aoumeur Hadj-Aïssa

  3. Université Claude Bernard, Lyon I, France

    Laurence Dubourg, Corinne Pondarré, Aoumeur Hadj-Aïssa & Pierre Cochat

  4. FRE CNRS 3310, Université Claude Bernard, Lyon I, France

    Laurence Dubourg, Dominique Sigaudo-Roussel & Pierre Cochat

  5. Institut d’Hématologie et d’Oncologie Pédiatrique et Centre de Références des Thalassémies, Hospices Civils de Lyon, Lyon, France

    Corinne Pondarré

  6. Exploration Fonctionnelle Rénale et Métabolique, Pavillon P–Hôpital Edouard Herriot, 5 place d’Arsonval, 69437, Lyon cedex 03, France

    Laurence Dubourg

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  1. Laurence Dubourg
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  2. Céline Laurain
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  3. Bruno Ranchin
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Correspondence to Laurence Dubourg.

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Dubourg, L., Laurain, C., Ranchin, B. et al. Deferasirox-induced renal impairment in children: an increasing concern for pediatricians. Pediatr Nephrol 27, 2115–2122 (2012). https://doi.org/10.1007/s00467-012-2170-4

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