Thiazide-associated hyponatremia in internal medicine patients: analysis of epidemiological and biochemical profiles

Postgrad Med. 2022 Jun;134(5):487-493. doi: 10.1080/00325481.2022.2063634. Epub 2022 Apr 15.

Abstract

Objectives: Thiazide-associated hyponatremia (TAH) is a clinically important side effect of the therapy with thiazide and thiazide-like diuretics. This study aims to analyze epidemiological, biochemical, and symptomatological profiles (including volume status) of patients admitted with TAH.

Methods: A retrospective hospital record study was performed. Epidemiological and biochemical parameters and symptoms were compared between the thiazide (n = 143) and non-thiazide (n = 282) groups. Patients in the thiazide group were classified as hypo-, normo-, or hypervolemic. Furthermore, the comparison of epidemiological, biochemical, partially pharmacotherapeutical, and symptomatological parameters between the hypovolemic and normovolemic TAH groups was performed.

Results: The thiazide group showed lower s-Na (p = 0.008), s-K (p < 0.001), s-Cl (p < 0.001), measured s-osmolality (p = 0.021), and eGFR (p < 0.001); higher s-urea (p < 0.001), s-creatinine (p = 0.023), s-glucose (p < 0.001), u-osmolality (p = 0.012), u-Na (p < 0.001), u-K (p = 0.023), and u-Cl (p < 0.001). Patients using thiazide were older (p < 0.001), more likely to be female (p = 0.011), and with symptoms corresponding more to chronic hyponatremia. Compared to the normovolemic group (n = 93; 65%), the hypovolemic patients (n = 47; 32.9%) showed higher s-urea (p = 0.005), s-creatinine (p = 0.045), and s-UA (p = 0.010); lower eGFR (p = 0.032), u-Na (p = 0.015), u-Cl (p = 0.016), anorexia (p < 0.001), and a higher frequency of furosemide use (p < 0.001).

Conclusions: Thiazide use is a crucial etiological cause of hypotonic hyponatremia among internal medicine inpatients, associated with more severe hyponatremia, but with no difference in the in-hospital mortality. Even in hypo-osmolar conditions of TAH, 32.9% of patients exhibited signs of volume depletion. FE-UA did not differ between the hypovolemic and the normovolemic patients in TAH conditions. Anorexia and the combination of thiazide together with furosemide, rather than thiazide use alone, were risk factors for hypovolemic hyponatremia without affecting FE-UA.

Keywords: Thiazide; hyponatremia; thiazide-associtated hyponatremia (TAH); thiazide-induced hyponatremia (TIH); uric acid.

MeSH terms

  • Anorexia / chemically induced
  • Anorexia / complications
  • Anorexia / drug therapy
  • Creatinine
  • Female
  • Furosemide
  • Humans
  • Hyponatremia* / chemically induced
  • Hyponatremia* / epidemiology
  • Hypovolemia / chemically induced
  • Internal Medicine
  • Male
  • Retrospective Studies
  • Sodium
  • Thiazides* / adverse effects
  • Urea

Substances

  • Thiazides
  • Furosemide
  • Urea
  • Sodium
  • Creatinine