Thiazide diuretics lower blood pressure and cardiovascular risk but can cause severe hyponatraemia. Researchers now demonstrate that thiazide-induced hyponatraemia is associated with a genetic variant in a distal nephron prostaglandin transporter. They propose that reduced prostaglandin reabsorption through this transporter facilitates activation of the prostaglandin EP4 receptor to increase water reabsorption.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Chow, K. M., Szeto, C. C., Wong, T. Y., Leung, C. B. & Li, P. K. Risk factors for thiazide-induced hyponatraemia. QJM 96, 911–917 (2003).
Frenkel, N. J. et al. 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. 33, 627–633 (2015).
Friedman, E., Shadel, M., Halkin, H. & Farfel, Z. Thiazide-induced hyponatremia. Reproducibility by single dose rechallenge and an analysis of pathogenesis. Ann. Intern. Med. 110, 24–30 (1989).
Clark, B. A., Shannon, R. P., Rosa, R. M. & Epstein, F. H. Increased susceptibility to thiazide-induced hyponatremia in the elderly. J. Am. Soc. Nephrol. 5, 1106–1111 (1994).
Ware, J. S. et al. Phenotypic and pharmacogenetic evaluation of patients with thiazide-induced hyponatremia. J. Clin. Invest. 127, 3367–3374 (2017).
Cesar, K. R. & Magaldi, A. J. Thiazide induces water absorption in the inner medullary collecting duct of normal and Brattleboro rats. Am. J. Physiol. 277, F756–F760 (1999).
Kim, G. H. et al. Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl co-transporter, and epithelial sodium channel. J. Am. Soc. Nephrol. 15, 2836–2843 (2004).
Olesen, E. T. & Fenton, R. A. Is there a role for PGE2 in urinary concentration? J. Am. Soc. Nephrol. 24, 169–178 (2013).
Dusing, R. et al. Interaction of bemetizide and indomethacin in the kidney. Br. J. Clin. Pharmacol. 16, 377–383 (1983).
Decaux, G., Prospert, F., Soupart, A. & Musch, W. Evidence that chronicity of hyponatremia contributes to the high urate clearance observed in the syndrome of inappropriate antidiuretic hormone secretion. Am. J. Kidney Dis. 36, 745–751 (2000).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
PowerPoint slides
Rights and permissions
About this article
Cite this article
Hoorn, E., Wetzels, J. Prostaglandins in thiazide-induced hyponatraemia: do they hold water?. Nat Rev Nephrol 13, 665–666 (2017). https://doi.org/10.1038/nrneph.2017.133
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrneph.2017.133
