title: Hydrochlorothiazide in CLDN16 mutation.
abstract: 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.
authors.affiliation: Klinik für Kinder und Jugendliche, Friedrich-Alexander-University of Erlangen-Nuremberg, Loschgestr. 15, D-91054 Erlangen, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Zimmermann
authors.forename: Christian
authors.initials: C
authors.lastname: Plank
authors.forename: Martin
authors.initials: M
authors.lastname: Konrad
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stöhr
authors.forename: Chara
authors.initials: C
authors.lastname: Gravou-Apostolatou
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
mesh_terms: D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000652:urine; D002648:Child; D002675:Child, Preschool; D057167:Claudins; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology* / Q000627:therapeutic use*; D053565:Hypercalciuria / Q000188:drug therapy* / Q000235:genetics; D007223:Infant; D008138:Loop of Henle / Q000187:drug effects*; D008274:Magnesium / Q000097:blood* / Q000652:urine; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency*; D009154:Mutation; D009397:Nephrocalcinosis / Q000188:drug therapy* / Q000235:genetics; D011188:Potassium / Q000097:blood / Q000652:urine; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D019108:Tight Junctions / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D057167:Claudins; D008565:Membrane Proteins; D049994:Sodium Potassium Chloride Symporter Inhibitors; C502010:claudin 16; D006852:Hydrochlorothiazide; D003404:Creatinine; D008274:Magnesium; D011188:Potassium; D002118:Calcium