Deferasirox effect on renal haemodynamic parameters in patients with transfusion‐dependent β thalassaemia

• Published in: British journal of haematology 2015-03, Vol.168 (6), p.882-890
• Main Authors: Piga, Antonio, Fracchia, Silvia, Lai, Maria E., Cappellini, Maria Domenica, Hirschberg, Raimund, Habr, Dany, Wegener, Antje, Bouillaud, Emmanuel, Forni, Gian Luca
• Format: Article
• Language: English
• Subjects: Adult; Benzoates - adverse effects; Benzoates - pharmacology; Benzoates - therapeutic use; beta-Thalassemia - blood; beta-Thalassemia - physiopathology; beta-Thalassemia - therapy; Biomarkers - blood; Biomarkers - urine; Chelation Therapy - adverse effects; Chelation Therapy - methods; Creatinine - blood; deferasirox; Female; Ferritins - blood; glomerular filtration rate; Glomerular Filtration Rate - drug effects; Hemodynamics - drug effects; Humans; Iron Chelating Agents - adverse effects; Iron Chelating Agents - pharmacology; Iron Chelating Agents - therapeutic use; iron chelation; Iron Overload - drug therapy; Iron Overload - etiology; Male; Middle Aged; Renal Circulation - drug effects; renal function; thalassaemia; Transfusion Reaction; Triazoles - adverse effects; Triazoles - pharmacology; Triazoles - therapeutic use; Young Adult
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.13217

Summary Some patients with β thalassaemia experience non‐progressive creatinine increases with deferasirox, mostly within normal limits; the mechanisms involved are not fully elucidated. The effects of deferasirox on renal haemodynamics, including glomerular filtration rate (GFR) and renal plasma flow (RPF), were investigated in a Phase I, open‐label study in β thalassaemia major patients with iron overload. Patients received deferasirox 30 mg/kg/d up to Week 8, followed by a 2‐week washout period, and extended treatment up to Week 104 with a 4‐week washout period. In the short‐term study (n = 11), mean GFR and RPF declined from baseline to Week 8 (mean [%] change:−9·2 [−9·5%] and −105·7 ml/min [−17·8%], respectively). A similar pattern was observed during the long‐term study (n = 5); mean GFR and RPF decreased up to Week 52 (−19·1 [−17·7%] and −155·6 ml/min [−26·1%]), with similar change at Week 104 (−18·4 [−17·2%] and −115·9 ml/min [−19·6%]). Measures returned to baseline values after each washout. Serum creatinine and creatinine clearance followed a similar pattern. Effects of deferasirox on renal haemodynamics were mild and reversible for up to 2 years of treatment, with no progressive worsening of renal function over time. www.clinicaltrials.gov: NCT00560820.