LAUSR

Dear Editors, We read with great interest the comprehensive overview by Ahlenstiel-Grunow et al. which recently appeared in Pediatric Nephrology [1]. The study documents the experience of the authors in switching patients with nephropathic cystinosis from the intermediate-release (IR) formulation of cysteamine to the extended-release (ER) formulation. Our clinical experience with the ER formulation of cysteamine, however, is quite different from that reported by Ahlenstiel-Grunow and colleagues. We currently manage five patients with nephropathic cystinosis in our outpatient clinic, of whom three (aged 12, 16 and 19 years) were switched from the IR formulation to the ER formulation in equivalent dose but had to be switched back to the IR formulation due to deterioration in disease control (2 patients) and sudden manifestation of severe side effects (1 patient). These patients had been treated with IR-cysteamine for 11, 16 and 19 years, respectively. Good disease control had been achieved in two of the three patients (aged 12 and 19 years, respectively) with IR-cysteamine. Themain reasons for conversion were very similar to those reported by Ahlenstiel-Grunow et al., namely, difficulties with night-time administration, nausea, and the foul taste and smell of IR-cysteamine. Patients 1 (12 years, male) and 2 (19 years, male) were treated with ER-cysteamine for 9 months. However, they experienced a deterioration in disease control reflected by increasing white blood cell cystine values and deterioration of renal function. Patient 1 had an estimated glomerular filtration rate (eGFR) of 70 ml/min/1.73 m when started on ERcysteamine and a eGFR of 33.3 ml/min/1.73m at the time he was switched back to IR-cysteamine. Similarly, the eGFR of Patient 2 decreased from 13.6 ml/min/1.73 m at the time of conversion to ER-cysteamine to 8.2 ml/min/1.73m during ER-cysteamine treatment. Increase in ER-cysteamine doses in those two patients resulted in worsening of abdominal pain after intake. As no intervention was able to alleviate the pain, both patients were switched back to IR-cysteamine. Disease control subsequently improved in terms of white blood cell cystine values, but the abdominal pain persists in patient 1. Patient 3 (16 years, male) had received a kidney transplant 6 months before conversion to ER-cysteamine. The reason for conversion to the ER formulation was that this patient’s cystinosis was not satisfactorily controlled with the IR formulation. However, upon conversion to ER-cysteamine the patient immediately suffered massive diarrhea, nausea and vomiting. He was directly switched back to IR-cysteamine, whereupon the diarrhea and vomiting stopped instantly. White blood cell cystine values are remain suboptimal, and the patient still complains of nausea related to drug intake, which compromises drug adherence. A fourth patient (female) directly started on ER-cysteamine after confirmation of the diagnosis at the age of 16months due to foreseeable difficulties with adherence and shows good disease control without side effects of the medication. The fifth patient (11 years, male) was not switched due to good disease control without noteworthy side effects and lack of difficulties with the night-time administration of IRcysteamine. Medical treatment of nephropathic cystinosis remains a challenge because of side effects, frequency of administration of medicine and often problematic adherence to the therapy. We agree with the authors that the development of the ER formulation of cysteamine is a step forward to improve treatment and opens treatment alternatives. However, after * Sören Bäumner [email protected]