Fanconi syndrome deferasirox

Of about 50 patients with P-thalassemia who were treated with deferasirox, four (three children and one woman) developed Fanconi syndrome that was probably related to the drug [16 ]. The use of deferasirox (30 mg/kg/day in the children, 38 mg/ kg/day in the adult time to onset not specified) was followed by severe proximal renal tubular dysfunction characterized by hypokalemia, hypophosphatemia, glycosuria, and a metabolic acidosis. All recovered on withdrawal of deferasirox and electrolyte supplementation. The three children simultaneously had mild infections (gastrointestinal in two, respiratory in one) the woman had no other susceptibility factors for tubular dysfunction. 

In another case deferasirox-associated acute renal insufficiency and Fanconi syndrome occurred in a 77wear-old man with hemochromatosis [15 ]. He developed severe hypokalemia (2.1 mmol/1), normoglycemic glycosuria, and aminoaciduria of neutral and acidic amino acids. His eGFR fell to 34 ml/minute/1.73 m. ... 

A few previous reports have suggested a connection between deferasirox and renal tubular damage. The prescribing package notes that the dose of deferasirox should be reduced if serum creatinine, a marker of kidney function and glomerular filtration, is elevated by more than 33% compared with serum creatinine prior to drug administration. Approximately 8% of deferasirox and its metabolites are excreted by the kidney, and previous in vitro studies have suggested that cells of the proximal renal tubule are sensitive to deferasirox toxicity. A case study was the first to provide biopsy evidence of deferasirox-mediated Fanconi syndrome [34 ]. 

Murphy N, Elramah M, Vats H, Zhong W, Chan MR. A case report of deferasirox-induced kidney it ury and Fanconi syndrome. WMJ August 2013 112(4) 177-80. 

---