NDT Advance Access published online on April 4, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl144
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1 Klinik für Kinder und Jugendliche der Friedrich-Alexander-Universität, Loschgestr. 15, D-91054 Erlangen, Germany
* To whom correspondence should be addressed. 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 x 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 x 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.
Received February 21, 2006
Accepted March 6, 2006
Original Article
Hydrochlorothiazide in CLDN16 mutation
Bettina Zimmermann 1,
Christian Plank 1,
Martin Konrad 2,
Wolfgang Stöhr 3,
Chara Gravou-Apostolatou 1,
Wolfgang Rascher 1,
and
Jörg Dötsch 1 *
2 Universitäts-Kinderklinik, Inselspital, CH-3010 Bern, Germany
3 Institut für Medizininformatik, Biometrie und Epidemiologie der Friedrich-Alexander-Universität, Waldstr. 6, D-91054 Erlangen, Germany
Jörg Dötsch, E-mail: joerg.doetsch{at}kinder.imed.uni-erlangen.de
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