The Effect of Thiazide Diuretics on Urinary Prostaglandin E2 Excretion and Serum Sodium in the General Population

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Abstract

Context:

Thiazide-induced hyponatremia is one of the most common forms of hyponatremia, but its pathogenesis is incompletely understood. Recent clinical data suggest links with prostaglandin E2 (PGE2) and a single nucleotide polymorphism (SNP) in the prostaglandin transporter gene (SLCO2A1), but it is unknown if these findings also apply to the general population.

Objective:

To study the associations between serum sodium, thiazide diuretics, urinary excretions of PGE2, and its metabolite (PGEM), and the rs34550074 SNP in SLCO2A1 in the general population.

Design:

Prospective population-based cohort study (Rotterdam Study).

Setting:

General population.

Participants:

2178 participants (65% female, age 64 +/- 8 years)

Intervention(s):

None.

Main Outcome:

Measure(s) Serum sodium levels.

Results:

Higher urinary PGE2 excretion was associated with lower serum sodium: difference in serum sodium for each 2-fold higher PGE2 -0.19 mmol/L [95% confidence interval (CI) -0.31 to -0.06], PGEM -0.29 mmol/L (95% CI -0.41 to -0.17). This association was stronger in thiazide users (per 2-fold higher PGE2 -0.73 vs -0.12 mmol/L and PGEM -0.6 vs -0.25 mmol/L, P for interaction <.05 for both). A propensity score matching analysis of thiazide vs non-thiazide users yielded similar results. The SNP rs34550074 was not associated with lower serum sodium or higher urinary PGE2 or PGEM excretion in thiazide or non-thiazide users.

Conclusion:

Serum sodium is lower in people with higher urinary PGE2 and PGEM excretion, and this association is stronger in thiazide users. This suggests that PGE2-mediated water reabsorption regulates serum sodium, which is relevant for the pathogenesis of hyponatremia in general and thiazide-induced hyponatremia specifically.
Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
DOIs
Publication statusE-pub ahead of print - 22 May 2024

Bibliographical note

© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.

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