NDT Advance Access originally published online on April 4, 2006
Nephrology Dialysis Transplantation 2006 21(8):2127-2132; doi:10.1093/ndt/gfl144
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Clinical Nephrology
Hydrochlorothiazide in CLDN16 mutation
1 Klinik für Kinder und Jugendliche der Friedrich-Alexander-Universität, Loschgestr. 15, D-91054 Erlangen, 2 Universitäts-Kinderklinik, Inselspital, CH-3010 Bern and 3 Institut für Medizininformatik, Biometrie und Epidemiologie der Friedrich-Alexander-Universität, Waldstr. 6, D-91054 Erlangen, Germany
Correspondence and offprint requests to: Jörg Dötsch, MD, Klinik für Kinder und Jugendliche, Friedrich-Alexander-University of Erlangen-Nuremberg, Loschgestr. 15, D-91054 Erlangen, Germany. Email: joerg.doetsch{at}kinder.imed.uni-erlangen.de
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.
Keywords: claudin-16; hydrochlorothiazide; hypercalciuria
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