Deferasirox-induced renal impairment in children: an increasing concern for pediatricians.
ABSTRACT 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.
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.
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.
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.
- SourceAvailable from: Shinya Toyokuni[Show abstract] [Hide abstract]
ABSTRACT: Asbestos was used worldwide in huge quantities in the past century. However, because of the unexpected carcinogenicity to mesothelial cells with an extremely long incubation period, many countries face this long-lasting social problem. Mesothelioma is often diagnosed in an advanced stage, for which no effective therapeutic protocols are yet established. We previously reported based on animal experiments that the major pathology in asbestos-induced mesothelial carcinogenesis is local iron overload. Here we undertook to find an effective strategy to prevent, delay or lower the malignant potential of mesothelioma during asbestos-induced carcinogenesis. We used intraperitoneal injections of crocidolite to rats. We performed a 16-week study to seek the maximal tolerated intervention for iron reduction via oral deferasirox administration or intensive phlebotomy. Splenic iron deposition was significantly decreased with either method, and we found that Perls' iron staining in spleen is a good indicator for iron reduction. We injected a total of 10 mg crocidolite at the age of 6 weeks, and the preventive measures were via repeated oral administration of 25-50 mg/kg/day deferasirox or weekly to bimonthly phlebotomy of 4-10 ml/kg/day. The animals were observed till 110 weeks. Deferasirox administration significantly increased the fraction of less malignant epithelioid subtype. Although we found a slightly prolonged survival in deferasirox-treated female rats, larger sample size and refinement of the current protocol are necessary to deduce the cancer-preventive effects of deferasirox. Still, our results suggest deferasirox serves as a potential preventive strategy in people already exposed to asbestos via iron reduction.Cancer Prevention Research 09/2013; · 4.89 Impact Factor
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ABSTRACT: Red blood cell transfusions are increasingly used in the management of various anemias, including thalassemia and sickle cell disease. Because the body lacks physiologic mechanisms for removing excess iron, transfusional iron overload is a common complication in children receiving regular transfusions. Iron chelation is necessary to remove the excess iron that causes injury to the heart, liver, and endocrine organs. Three chelators, deferoxamine, deferasirox, and deferiprone, are currently available in the United States. When choosing a chelator regimen, patients, parents, and providers may consider a variety of factors, including the severity of iron overload, administration schedule, and adverse effect profile.Pediatric Clinics of North America 12/2013; 60(6):1393-406. · 1.78 Impact Factor
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ABSTRACT: Transfusion-dependent children, mostly with thalassaemia major, but also and occasionally to a more significant degree, with inherited bone marrow failures, can develop severe iron overload in early life. Moreover, chronic conditions associated with ineffective erythropoiesis, such as non-transfusion-dependent thalassaemia (NTDT), may lead to iron overload through increased gut absorption of iron starting in childhood. Currently, the goal of iron chelation has shifted from treating iron overload to preventing iron accumulation and iron-induced end-organ complications, in order to achieve a normal pattern of complication-free survival and of quality of life. New chelation options increase the likelihood of achieving these goals. Timely initiation, close monitoring and continuous adjustment are the cornerstones of optimal chelation therapy in children, who have a higher transfusional requirements compared to adults in order to reach haemoglobin levels adequate for normal growth and development. Despite increased knowledge, there are still uncertainties about the level of body iron at which iron chelation therapy should be started and about the appropriate degree of iron stores' depletion.British Journal of Haematology 03/2014; · 4.94 Impact Factor