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

• Published in: The journal of clinical endocrinology and metabolism Vol. 109; no. 10; pp. 2444 - 2451
• Main Authors: Geurts, Frank, Rudolphi, Crissy F, Pelouto, Anissa, van der Burgh, Anna C, Salih, Mahdi, Imenez Silva, Pedro Henrique, Fenton, Robert A, Chaker, Layal, Hoorn, Ewout J
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 22.05.2024
• Subjects: electrolyte disorders; single nucleotide polymorphism; hyponatremia; Electrolyte disorders; Hyponatremia; Single nucleotide polymorphism
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgae352

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.