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Renal physiology: Prostaglandins in thiazide-induced hyponatraemia: do they hold water?

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.

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  1. 1.

    , , , & Risk factors for thiazide-induced hyponatraemia. QJM 96, 911–917 (2003).

  2. 2.

    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).

  3. 3.

    , , & Thiazide-induced hyponatremia. Reproducibility by single dose rechallenge and an analysis of pathogenesis. Ann. Intern. Med. 110, 24–30 (1989).

  4. 4.

    , , & Increased susceptibility to thiazide-induced hyponatremia in the elderly. J. Am. Soc. Nephrol. 5, 1106–1111 (1994).

  5. 5.

    et al. Phenotypic and pharmacogenetic evaluation of patients with thiazide-induced hyponatremia. J. Clin. Invest. 127, 3367–3374 (2017).

  6. 6.

    & Thiazide induces water absorption in the inner medullary collecting duct of normal and Brattleboro rats. Am. J. Physiol. 277, F756–F760 (1999).

  7. 7.

    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).

  8. 8.

    & Is there a role for PGE2 in urinary concentration? J. Am. Soc. Nephrol. 24, 169–178 (2013).

  9. 9.

    et al. Interaction of bemetizide and indomethacin in the kidney. Br. J. Clin. Pharmacol. 16, 377–383 (1983).

  10. 10.

    , , & 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).

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Author information


  1. Department of Internal Medicine, Division of Nephrology & Transplantation, Erasmus Medical Center, Room H-438, PO Box 2040, 3000 CA, Rotterdam, Netherlands.

    • Ewout J. Hoorn
  2. Department of Nephrology 464, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, Netherlands.

    • Jack F. M. Wetzels


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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ewout J. Hoorn.