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Hydrochlorothiazide in CLDN16 mutation

Zimmermann, Bettina ; Plank, Christian ; Konrad, Martin ; Stöhr, Wolfgang ; Gravou-Apostolatou, Chara ; Rascher, Wolfgang ; Dötsch, Jörg

In: Nephrology Dialysis Transplantation, 2006, vol. 21, no. 8, p. 2127-2132

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    Title
    • Hydrochlorothiazide in CLDN16 mutation
    Author
    • Zimmermann, Bettina. Klinik für Kinder und Jugendliche der Friedrich-Alexander-Universität, Loschgestr. 15, D-91054 Erlangen
    • Plank, Christian. Klinik für Kinder und Jugendliche der Friedrich-Alexander-Universität, Loschgestr. 15, D-91054 Erlangen
    • Konrad, Martin. Universitäts-Kinderklinik, Inselspital, CH-3010 Bern and
    • Stöhr, Wolfgang. Institut für Medizininformatik, Biometrie und Epidemiologie der Friedrich-Alexander-Universität, Waldstr. 6, D-91054 Erlangen, Germany
    • Gravou-Apostolatou, Chara. Klinik für Kinder und Jugendliche der Friedrich-Alexander-Universität, Loschgestr. 15, D-91054 Erlangen
    • Rascher, Wolfgang. Klinik für Kinder und Jugendliche der Friedrich-Alexander-Universität, Loschgestr. 15, D-91054 Erlangen
    • Dötsch, Jörg. Klinik für Kinder und Jugendliche der Friedrich-Alexander-Universität, Loschgestr. 15, D-91054 Erlangen
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Nephrology Dialysis Transplantation, 2006, vol. 21, no. 8, p. 2127-2132. Oxford University Press
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:292263
    Summary
    Background. Hydrochlorothiazide (HCT) is applied in the therapy of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) caused by claudin-16 (CLDN16) mutation. However, the short-term efficacy of HCT to reduce hypercalciuria in FHHNC has not yet been demonstrated in a clinical trial. Methods. Four male and four female patients with FHHNC and CLDN16 mutation, under long-standing HCT therapy (0.4-1.2 mg/kg, median 0.9 mg/kg, dose according to calciuria), aged 0.7-22.4 years, were included in a clinical study to investigate the effect of HCT on calciuria. The study design consisted of three periods: continued therapy for 4 weeks, HCT withdrawal for 6 weeks and restart of therapy at the same dose for 4 weeks. Calciuria and magnesiuria were assessed weekly as Ca/creat and Mg/creat ratio, every 2 weeks in 24 h urine, and serum Mg, K and kaliuria (s-Mg, s-K and K/creat) at weeks 0, 6, 10 and 14. The data of each study period were averaged and analysed by Friedman and Wilcoxon test. Results. Ca/creat was significantly reduced by HCT (median before/at/after withdrawal 0.76/1.24/0.77 mol/mol creat; n = 8, P<0.05). The reduction of Ca/24 h by HCT was not statistically significant (0.13/0.19/0.13 mmol/kg × 24 h; n = 5). Serum Mg (0.51/0.64/0.56 mmol/l; n = 8, P<0.05) and Serum K (3.65/4.35/3.65 mmol/l; n = 8, P<0.05) were significantly higher during withdrawal. However, Mg/creat (0.98/0.90/0.90 mol/mol creat; n = 8), Mg/24 h (0.14/0.12/0.18 mmol/kg × 24h; n = 5) and K/creat (6.3/8.4/6.2 mol/mol creat; n = 8) remained statistically unchanged during withdrawal. Conclusions. We demonstrated that HCT is effective in reducing hypercalciuria due to CLDN16 mutation on a short-term basis. However, the efficacy of HCT to attenuate disease progression remains to be elucidated