Hyperchloremic metabolic acidosis due to deferasirox in a patient with beta thalassemia major

Abstract

Objective: To report a case of hyperchloremic metabolic acidosis in a patient with beta thalassemia major secondary to treatment with deferasirox due to iron overload.

Case summary: A 58-year-old white female with beta thalassemia major was admitted with fever, fatigue, abnormal liver function test results, and hyperchloremic metabolic acidosis (lactate dehydrogenase 494 U/L, aspartate aminotransferase 167 U/L, alanine aminotransferase 250 U/L, gamma-glutamyl transferase 102 U/L, total bilirubin 3.79 mg/dL, direct bilrubin 2.37, potassium 3.3 mEq/L, PO(2) 81.4 mm Hg, PCO(2) 29.4 mm Hg, HCO(3) 16 mEq/L, pH 7.35, chloride 116 mEq/L, anion gap 7.5 mEq/L). Twenty-five days before admission the patient decided to discontinue treatment with deferoxamine for chronic iron overload and continue treatment with oral deferasirox 1500 mg/day. Despite extended clinical and laboratory examination, no obvious cause of fever, hepatitis, or hyperchloremic metabolic acidosis was revealed. Diagnosis was compatible with tubular dysfunction, drug-induced hepatitis, and hypersensitivity reaction due to deferasirox. All pathological findings were fully reversible and our patient had an excellent outcome.

Discussion: The presence of tubular dysfunction should be considered in any patient with otherwise unexplained hyperchloremic metabolic acidosis. In our patient, other potential causes of metabolic hyperchloremic acidosis were ruled out. Toxic effects of deferasirox are probably caused by chelation of mitochondrial iron, leading to adenosine triphosphate depletion in tubular epithelial cells. Use of the Naranjo probability scale revealed that the adverse reaction was probable.

Conclusions: Kidney toxicity may be a major issue in the management of patients receiving deferasirox. Our case indicates a potential risk of renal toxicity with the presence of tubular dysfunction and hyperchloremic metabolic acidosis in patients undergoing treatment with deferasirox.