Risk of thiazide-induced hyponatremia in patients with hypertension

Am J Med. 2011 Nov;124(11):1064-72. doi: 10.1016/j.amjmed.2011.06.031.


Background: Although hyponatremia is a well-recognized complication of treatment with thiazide diuretics, the risk of thiazide-induced hyponatremia remains uncertain in routine care.

Methods: We conducted a retrospective cohort study using a multicenter clinical research registry to identify 2613 adult outpatients that were newly treated for hypertension between January 1, 2000 and December 31, 2005 at 2 teaching hospitals in Boston, Massachusetts, and followed them for up to 10 years.

Results: Two hundred twenty patients exposed to ongoing thiazide therapy were compared with 2393 patients who were not exposed. In the exposed group, 66 (30%) developed hyponatremia (sodium ≤130 mmol/L). The adjusted incidence rate of hyponatremia was 140 cases per 1000 person-years for patients treated with thiazides, compared with 87 cases per 1000 person-years in those without thiazides. Patients exposed to thiazides were more likely to develop hyponatremia (adjusted incidence rate ratio, 1.61; 95% confidence interval [CI], 1.15-2.25). There was no significant difference in the risk of hospitalizations associated with hyponatremia (adjusted rate ratio, 1.04; 95% CI, 0.46-2.32) or mortality (adjusted rate ratio, 0.41; 95% CI, 0.12-1.42). The number needed to harm (to result in one excess case of incident hyponatremia in 5 years) was 15.02 (95% CI, 7.88-160.30).

Conclusions: Approximately 3 in 10 patients exposed to thiazides who continue to take them develop hyponatremia.

MeSH terms

  • Adult
  • Aged
  • Cross-Sectional Studies
  • Female
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / epidemiology
  • Hyponatremia / chemically induced*
  • Hyponatremia / epidemiology
  • Incidence
  • Male
  • Massachusetts
  • Middle Aged
  • Numbers Needed To Treat
  • Retrospective Studies
  • Risk Factors
  • Sodium Chloride Symporter Inhibitors / adverse effects*
  • Sodium Chloride Symporter Inhibitors / therapeutic use


  • Sodium Chloride Symporter Inhibitors