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
Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 2024 Sep 16;109(10):2444-2451. doi: 10.1210/clinem/dgae352.
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.
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.
Prospective population-based cohort study (Rotterdam Study).
General population.
2178 participants (65% female, age 64 ± 8 years).
INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Serum sodium levels.
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.
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.
噻嗪类药物所致低钠血症是最常见的低钠血症形式之一，但其发病机制尚未完全明确。近期临床数据表明其与前列腺素E2（PGE2）及前列腺素转运体基因（SLCO2A1）中的单核苷酸多态性（SNP）有关，但这些发现是否也适用于普通人群尚不清楚。
研究普通人群中血清钠、噻嗪类利尿剂、PGE2及其代谢产物（PGEM）的尿排泄量以及SLCO2A1基因中的rs34550074 SNP之间的关联。
基于人群的前瞻性队列研究（鹿特丹研究）。
普通人群。
2178名参与者（65%为女性，年龄64±8岁）。
无。
血清钠水平。
尿PGE2排泄量增加与血清钠降低相关：PGE2每升高2倍，血清钠差异为-0.19 mmol/L [95%置信区间（CI）-0.31至-0.06]，PGEM为-0.29 mmol/L（95% CI -0.41至-0.17）。在使用噻嗪类药物的人群中这种关联更强（PGE2每升高2倍，差异为-0.73对-0.12 mmol/L，PGEM为-0.6对-0.25 mmol/L，两者交互作用P均<0.05）。对使用噻嗪类药物与未使用噻嗪类药物的人群进行倾向评分匹配分析得到了相似结果。rs34550074 SNP与使用或未使用噻嗪类药物人群的血清钠降低或尿PGE2及PGEM排泄量增加无关。
尿PGE2和PGEM排泄量较高的人群血清钠较低，且这种关联在使用噻嗪类药物的人群中更强。这表明PGE2介导的水重吸收调节血清钠，这对于一般低钠血症尤其是噻嗪类药物所致低钠血症的发病机制具有重要意义。
