American Journal of Kidney Diseases
Volume 52, Issue 6 , Pages 1084-1095, December 2008

Effect of Hydrochlorothiazide on Urinary Calcium Excretion in Dent Disease: An Uncontrolled Trial

  • Anne Blanchard, MD, PhD

      Affiliations

    • Université Paris 5, Faculté de Médecine Paris Descartes, France
    • Assistance Publique-Hôpitaux de Paris, Hôpital Européen George Pompidou, France
    • Centre d'Investigations Cliniques 9201, France
    • Corresponding Author InformationAddress correspondence to Anne Blanchard, MD, PhD, Centre d'Investigation Cliniques, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, F-75015 Paris
  • ,
  • Rosa Vargas-Poussou, MD, PhD

      Affiliations

    • Université Paris 5, Faculté de Médecine Paris Descartes, France
    • Assistance Publique-Hôpitaux de Paris, Hôpital Européen George Pompidou, France
    • Département de Génétique, France
    • INSERM U772, Paris, France
  • ,
  • Severine Peyrard, MSc

      Affiliations

    • Assistance Publique-Hôpitaux de Paris, Hôpital Européen George Pompidou, France
    • Centre d'Investigations Cliniques 9201, France
  • ,
  • Agnes Mogenet, MD

      Affiliations

    • Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfant Malade, France
    • Centre d'Investigations Cliniques, France
  • ,
  • Veronique Baudouin, MD, PhD

      Affiliations

    • Service de Néphrologie, France
    • Faculté de Médecine, Université Paris 7, France
    • Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, France
  • ,
  • Bernard Boudailliez, MD, MSc

      Affiliations

    • Université de Picardie, faculté de médecine, Assistance Publique-Hôpitaux de Paris, France
    • Centre Hospitalier Amiens Sud, Département de Néphrologie Pédiatrique, France
  • ,
  • Marina Charbit, MD

      Affiliations

    • Université Paris 5, Faculté de Médecine Paris Descartes, France
    • Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfant Malade, France
    • Service de Néphrologie, France
  • ,
  • George Deschesnes, MD, PhD

      Affiliations

    • Service de Néphrologie, France
    • Faculté de Médecine, Université Paris 7, France
    • Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, France
  • ,
  • Nadia Ezzhair, MD

      Affiliations

    • Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, France
  • ,
  • Chantal Loirat, MD, PhD

      Affiliations

    • Service de Néphrologie, France
    • Faculté de Médecine, Université Paris 7, France
    • Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, France
  • ,
  • Marie-Alice Macher, MD, PhD

      Affiliations

    • Service de Néphrologie, France
    • Faculté de Médecine, Université Paris 7, France
    • Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, France
  • ,
  • Patrick Niaudet, MD, PhD

      Affiliations

    • Université Paris 5, Faculté de Médecine Paris Descartes, France
    • Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfant Malade, France
    • Faculté de Médecine, Université Paris 7, France
  • ,
  • Michel Azizi, MD, PhD

      Affiliations

    • Université Paris 5, Faculté de Médecine Paris Descartes, France
    • Assistance Publique-Hôpitaux de Paris, Hôpital Européen George Pompidou, France
    • Centre d'Investigations Cliniques 9201, France

Received 26 March 2008; accepted 1 August 2008. published online 03 November 2008.

Background

Thiazide doses equivalent to 1 to 2 mg/kg/d of hydrochlorothiazide (HCTZ) have been proposed to correct hypercalciuria and prevent kidney failure in patients with Dent disease. However, they can cause adverse metabolic effects in the long term. In treating hypertension in children, lower thiazide doses have been shown to be as effective and well tolerated.

Study Design

Uncontrolled trial, with forced-titration sequential open-label study design.

Setting & Participants

7 boys with genetically confirmed Dent disease and mild phenotype (neither overt sodium wasting nor kidney failure).

Intervention

After a 1-month run-in period, patients sequentially received amiloride (5 mg/d) alone (1 month) and then for 3 periods of 2 months in association with increasing doses of HCTZ (<0.2, 0.2 to 0.4, and 0.4 to 0.8 mg/kg/d).

Outcomes

Urinary calcium excretion and extracellular volume indicators.

Measurements

At the end of each period, 2 daily 24-hour urinary collections were performed on the days preceding admission. Blood and spot urine samples also were collected.

Results

A greater HCTZ dose increased renin, aldosterone, and plasma protein concentrations. Amiloride alone had no effect on calcium excretion. The greatest HCTZ doses decreased spot urinary calcium excretion by 42% compared with baseline (median, 0.3; minimum, maximum, 0.2, 0.8 versus median, 0.8; minimum, maximum, 0.4, 1.1, respectively; P = 0.03). However, patients developed adverse reactions, including muscle cramps (n = 2), biological (n = 7) or symptomatic hypovolemia (n = 1), hypokalemia (n = 4), and hyponatremia (n = 1), which all corrected after treatment withdrawal.

Limitation

Small sample size and absence of a control group.

Conclusion

HCTZ doses greater than 0.4 mg/kg/d decreased calcium excretion, but were associated with significant adverse events. Thiazide diuretic therapy should be considered with caution in children with Dent disease.

Index Words: Dent disease, nephrolithiasis, clinical trial, thiazides

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 Trial registration: ClinicalTrials.gov; study number: NCT00638482.

 Originally published online as doi:10.1053/j.ajkd.2008.08.021 on November 3, 2008.

PII: S0272-6386(08)01347-4

doi:10.1053/j.ajkd.2008.08.021

American Journal of Kidney Diseases
Volume 52, Issue 6 , Pages 1084-1095, December 2008