Comment on: ‘Lanthanum carbonate possibly responsible for acute liver failure in a patient with Child–Pugh stage A liver cirrhosis’

Recent advances in understanding the clinical and genetic heterogeneity of Dent's disease. D'mello RG et al. Responsiveness of hyper-calciuria to thiazide in Dent's disease. Acute interstitial nephritis associated with thiazide diuretics. Clinical and pathologic observations in three cases. Effect of hy-drochlorothiazide on urinary calcium excretion in Dent disease: an uncontrolled trial. Sir, De Leeuw and colleagues reported decompensation of existing liver disease in a patient with a complex history including alcohol-induced liver cirrhosis, pancreatitis and secondary diabetes [1]. The patient required hospitalization due to decreased consciousness and somnolence. The authors , noting a temporal association with lanthanum carbon-ate therapy, proposed that there was a causal relationship. This patient report is highly confounded by a number of factors, including concomitant medication and hypophos-phataemia, which are also credible explanations for the pa-tient's presentation. Firstly, the patient was taking lorazepam, which can cause coma in patients with reduced hepatic metabolism. Secondly , following dialysis the patient was profoundly hy-pophosphataemic. This is a recognized cause of irritability, paraesthaesia, confusion, convulsions and coma [2]. Evaluation of the published data on lanthanum carbonate (FOSRENOL R , Shire Pharmaceuticals, Basingstoke, UK) shows that the bioavailability is ∼0.001% and the small fraction of lanthanum absorbed is not metabolized. Animal studies have demonstrated that the presence of lanthanum in the liver is consistent with hepatic excretion via a lysosomal transcellular transport mechanism [3,4]. A long-term follow-up of clinical trial cohorts has included liver function tests and has not demonstrated any evidence of acute or chronic liver toxicity during 2 years of therapy compared to standard therapy. In uncontrolled studies, subjects have been exposed to lanthanum carbonate for up to 6 years [5,6]. In addition to over 5000 subjects in clinical studies, there is now over 60000 patient-years of post-marketing experience with lanthanum carbonate. Although no specific studies were done in patients with liver impairment, there is insufficient evidence to assume that lanthanum carbonate may contribute to a worsening of liver function in this patient population. Editorial Note: Dr De Leeuw et al. had been invited to reply to this letter but we did not receive a response in time.