Abstract
Background
Thiazide diuretics are a mainstay in the management of hypertension and often associated
with dyselectrolytemias. We investigated the prevalence of and risk factors for hyponatremia
and hypokalemia in thiazide users, substance-specific differences, and the association
of thiazides with syncope and falls.
Methods
In this cross-sectional analysis all patients admitted to an interdisciplinary emergency
department in Switzerland between January 1, 2017, and December 31, 2018, with measurements
of serum sodium and potassium were included. Data regarding serum electrolytes and
creatinine were analyzed to classify for dysnatremias, dyskalemias, and acute kidney
injury. Chart reviews were performed to screen for syncope or falls.
Results
A total of 1604 patients (7.9%) took thiazides. Acute kidney injury was significantly
more common in thiazide users (22.1 vs 7%, P < .0001). Hyponatremia (22.1 vs 9.8%, P < .0001) and hypokalemia (19 vs 11%, P < .0001) were more frequent with thiazides. Thiazide use together with higher age
and female sex were independent predictors of hyponatremia and hypokalemia. A dose-dependent
effect was found for electrolyte disorders, and there was a variance in risk between
the investigated substances with chlorthalidone bearing the highest and hydrochlorothiazide
the lowest risk. Patients taking thiazide diuretics had significantly more episodes
of syncope and falls.
Conclusions
Thiazide use is a clear risk factor for hyponatremia and hypokalemia. The effect appears
to be dose-dependent and highly variable depending on the substance. Syncope and falls
seem to be causally related to thiazide use. Especially in patients who are elderly,
female, and prone to falls, the use of thiazide diuretics should be thoroughly questioned.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The American Journal of MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Thiazide-associated hyponatremia: clinical manifestations and pathophysiology.Am J Kidney Dis. 2020; 75: 256-264
- 2020 International Society of Hypertension Global Hypertension Practice Guidelines.Hypertension. 2020; 75: 1334-1.57
- Impact of diuretic therapy-associated electrolyte disorders present on admission to the emergency department: a cross-sectional analysis.BMC Med. 2013; 11: 83
- Thiazide but not loop diuretics is associated with hypomagnesaemia in the general population.Pharmacoepidemiol Drug Saf. 2018; 27: 1166-1173
- Thiazide-associated hyponatremia, report of the hyponatremia registry: an observational multicenter international study.Am J Nephrol. 2017; 45: 420-430
- A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?.Br J Clin Pharmacol. 2015; 79: 566-577
- Thiazide-induced hyponatremia. Reproducibility by single dose rechallenge and an analysis of pathogenesis.Ann Intern Med. 1989; 110: 24-30
- Thiazide-induced hyponatraemia is associated with increased water intake and impaired urea-mediated water excretion at low plasma antidiuretic hormone and urine aquaporin-2.J Hypertens. 2015; 33: 627-633
- Hydrochlorothiazide in the treatment of hypertension. The effects on blood volume, exchangeable sodium and blood pressure.Acta Med Scand. 1968; 183: 317-321
- Diuretic-induced hyponatremia.Ann Intern Med. 1971; 75: 853-863
- Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability.Hypertension. 2004; 43: 4-9
- Improving outcomes from acute kidney injury: report of an initiative.Am J Kidney Dis. 2007; 50: 1-4
- Risk of thiazide-induced hyponatremia in patients with hypertension.Am J Med. 2011; 124: 1064-1072
- Phenotypic and pharmacogenetic evaluation of patients with thiazide-induced hyponatremia.J Clin Invest. 2017; 127: 3367-3374
- Clinical and genetic factors associated with thiazide-induced hyponatremia.Medicine (Baltimore). 2015; 94: e1422
- Genetic predictors of thiazide-induced serum potassium changes in nondiabetic hypertensive patients.Hypertens Res. 2014; 37: 759-764
- Age-related variety in electrolyte levels and prevalence of dysnatremias and dyskalemias in patients presenting to the emergency department.Gerontology. 2014; 60: 420-423
- Influence of gender on renal thiazide diuretic receptor density and response.J Am Soc Nephrology. 1994; 5: 1112-1119
Li J, Xu S, Yang L, et al. Sex difference in kidney electrolyte transport II: impact of K+ intake on thiazide-sensitive cation excretion in male and female mice. Am J Renal Physio. 201; 317:F967-977.
- Development of a hyponatremia screening tool (ABCDF-S score) for patients with hypertension using thiazide diuretic agents.J Clin Pharm Ther. 2020; 45: 997-1005
- The silent epidemic of thiazide-induced hyponatremia.J Clin Hypertens (Greenwich). 2008; 10: 477-484
- Thiazide diuretic prescription and electrolyte abnormalities in primary care.Br J Clin Pharmacol. 2006; 61: 87-95
- Acute hyperkalemia in the emergency department: a summary from a Kidney Disease: Improving Global Outcomes conference.Eur J Emerg Med. 2020; 27: 329-337
- Thiazide diuretics, potassium, and the development of diabetes: a quantitative review.Hypertension. 2006; 48: 219-224
- Increased susceptibility to thiazide-induced hyponatremia in the elderly.J Am Soc Nephrol. 1994; 5: 1106-1111
- Thiazide-associated hyponatremia in the elderly: what the clinician needs to know.J Geriatric Cardiol. 2016; 13: 175-182
Article Info
Publication History
Published online: May 08, 2021
Footnotes
Funding: None.
Conflicts of Interest: GL reports personal fees from Bayer, Daiichi-Sankyo, Otsuka and non-financial support from Otsuka, GSK, and Pierre Fabre. SR, SB, G-CF, CS, AE report none.
Authorship: All authors had access to the data and a role in writing this manuscript.
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
