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Abstract: SA-OR38

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

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical


  • Rudolphi, Crissy Froeling, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • Geurts, Frank, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • Pelouto, Anissa, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • van der Burgh, Anna C., Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • Imenez Silva, Pedro Henrique, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • Salih, Mahdi, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • Chaker, Layal, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • Hoorn, Ewout J., Erasmus MC, Rotterdam, Zuid-Holland, Netherlands

Group or Team Name

  • Rotterdam Kidney Lab.

Recent data suggest that thiazide-induced hyponatremia (TIH) is induced by prostaglandin E2 (PGE2)-mediated water reabsorption and that people with a single nucleotide polymorphism (SNP) in SLCO2A1 are more susceptible for TIH. Here, we hypothesize that higher urinary PGE2 excretion is also associated with lower serum sodium in the general population and that this association is stronger in thiazide users.


PGE2 and its metabolite PGEM were measured in spot urines from the population-based Rotterdam Study cohort and expressed as ratio with creatinine. The association between PGE2 and serum sodium and its interaction with thiazide use was analyzed using regression analysis with adjustments for potential confounders (sex, age, BMI, baseline eGFR, smoking status, systolic blood pressure, ACE-inhibitor use). A propensity score-matched cohort was generated by matching on the same confounders in addition to serum potassium and diabetes status. The contribution of SNPs was analyzed using genome wide association studies (GWAS).


2178 patients were included in the analysis (65% female, age 64 ± 8 years). Thiazide users (n=190) had a significantly lower serum sodium compared to non-thiazide users (140.9 vs. 141.3 mmol/l, p=0.007) but had similar urinary PGE2 (101.7 vs. 101.5 pg/mmol, p=0.7) and PGEM (55.6 vs. 56.3 pg/mmol, p=0.6) excretions. Urinary PGE2 and PGEM excretions were negatively associated with serum sodium in the multivariable analysis (PGE2: p=0.002, PGEM: p<0.001) and this association was stronger in thiazide users (Figure 1). Similar findings were observed in the propensity score matched cohort. The GWAS data is currently being analyzed.


Urinary PGE2 and PGEM excretions are higher in people with lower serum sodium, and this association is stronger in thiazide users. Our findings provide further evidence for the role of PGE2 in renal water handling, even within the normal range of serum sodium, and its potential contribution to hyponatremia and TIH.