Laurence Dubourg1,2,3,4,5, Céline Laurain6, Bruno Ranchin6, Corinne Pondarré7,8, Aoumeur Hadj-Aïssa9,7, Dominique Sigaudo-Roussel10, Pierre Cochat6,7,10. 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@chu-lyon.fr. 2. Exploration Fonctionnelle Rénale et Métabolique, Hospices Civils de Lyon, Lyon, France. laurence.dubourg@chu-lyon.fr. 3. Université Claude Bernard, Lyon I, France. laurence.dubourg@chu-lyon.fr. 4. FRE CNRS 3310, Université Claude Bernard, Lyon I, France. laurence.dubourg@chu-lyon.fr. 5. Exploration Fonctionnelle Rénale et Métabolique, Pavillon P-Hôpital Edouard Herriot, 5 place d'Arsonval, 69437, Lyon cedex 03, France. laurence.dubourg@chu-lyon.fr. 6. Centre de Référence des Maladies Rénales Rares, Service de Néphrologie et Rhumatologie Pédiatriques, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France. 7. Université Claude Bernard, Lyon I, France. 8. Institut d'Hématologie et d'Oncologie Pédiatrique et Centre de Références des Thalassémies, Hospices Civils de Lyon, Lyon, France. 9. Exploration Fonctionnelle Rénale et Métabolique, Hospices Civils de Lyon, Lyon, France. 10. FRE CNRS 3310, Université Claude Bernard, Lyon I, France.
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 m(2)) 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 m(2) and seven patients with a GFR of <100 mL/min per 1.73 m(2). 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.
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 m(2)) 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 m(2) and seven patients with a GFR of <100 mL/min per 1.73 m(2). 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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