Hendriksen L C, Mouissie M S, Herings R M C, van der Linden P D, Visser L E
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
Department of Pharmacy, Tergooi MC, Hilversum, Netherlands.
Front Pharmacol. 2024 Aug 6;15:1409271. doi: 10.3389/fphar.2024.1409271. eCollection 2024.
Hyponatremia is a common electrolyte disturbance and known adverse drug reaction of diuretics. Women tend to be more susceptible for diuretic associated hyponatremia. The aim of this study was to find more evidence whether women have a higher risk of diuretic associated hyponatremia than men measured at hospital admission for specific diuretic groups and whether there is a sex difference in risk of severity of hyponatremia.
All patients using a diuretic and admitted for any reason to Tergooi MC and Haga Teaching hospital in the Netherlands between the 1st of January 2017 and the 31st of December 2021, with recorded sodium levels at admission were included in this study. Cases were defined as patients with a sodium level <135 mmol/L, while control patients had a sodium level ≥135 mmol/L at admission. Logistic regression analysis was used to calculate odds ratios (OR) with 95% CIs for women versus men and adjusted for potential confounding covariables (age, body mass index, potassium serum level, systolic and diastolic blood pressure, estimated glomerular filtration rate, number of diuretics, comedications and comorbidities). Stratified analyses were conducted for specific diuretic groups (thiazides, loop diuretics and aldosterone antagonists), and adjusted for dose. Furthermore, stratified analyses were performed by severity of hyponatremia (severe: <125 mmol/L), mild: 125-134 mmol/L).
A total of 2,506 patients (50.0% women) were included, of which 516 had hyponatremia at admission (20.6%, 56.2% women). Women had a statistically significantly higher risk for hyponatremia at admission than men (OR 1.37; 95% CI 1.12-1.66) and after adjustment for potential risk factors (ORadj 1.55; 95% CI 1.22-1.98). Stratified analyses showed increased odds ratios for thiazides (ORadj 1.35; 95% CI 1.00-1.83) and loop diuretics (ORadj 1.62; 95% CI 1.19-2.19) among women. Use of aldosterone antagonists was also increased but not statistically significant (ORadj 1.15; 95% CI 0.73-1.81). Women had a statistically higher risk to develop mild and severe hyponatremia than men (ORadj 1.36; 95% CI 1.10-1.68 and ORadj 1.96; 95%CI 1.04-3.68, respectively).
Women have a higher risk of a hospital admission associated with hyponatremia while using diuretics than men. Further research is necessary to provide sex-specific recommendations.
低钠血症是一种常见的电解质紊乱，也是利尿剂已知的不良反应。女性往往更容易发生与利尿剂相关的低钠血症。本研究的目的是寻找更多证据，以确定在因特定利尿剂组入院时，女性发生与利尿剂相关的低钠血症的风险是否高于男性，以及低钠血症严重程度的风险是否存在性别差异。
纳入2017年1月1日至2021年12月31日期间因任何原因使用利尿剂并入住荷兰特尔古伊MC医院和哈加教学医院且入院时记录了钠水平的所有患者。病例定义为入院时钠水平<135 mmol/L的患者，而对照患者入院时钠水平≥135 mmol/L。采用逻辑回归分析计算女性与男性相比的比值比（OR）及95%置信区间，并对潜在的混杂协变量（年龄、体重指数、血清钾水平、收缩压和舒张压、估计肾小球滤过率、利尿剂数量、合并用药和合并症）进行校正。对特定利尿剂组（噻嗪类、袢利尿剂和醛固酮拮抗剂）进行分层分析，并对剂量进行校正。此外，根据低钠血症的严重程度（重度：<125 mmol/L，轻度：125 - 134 mmol/L）进行分层分析。
共纳入2506例患者（50.0%为女性），其中516例入院时患有低钠血症（20.6%，女性占56.2%）。女性入院时发生低钠血症的风险在统计学上显著高于男性（OR 1.37；95% CI 1.12 - 1.66），在对潜在风险因素进行校正后（校正OR 1.55；95% CI 1.22 - 1.98）。分层分析显示，女性使用噻嗪类药物（校正OR 1.35；95% CI 1.00 - 1.83）和袢利尿剂（校正OR 1.62；95% CI 1.19 - 2.19）的比值比增加。使用醛固酮拮抗剂的情况也有所增加，但无统计学意义（校正OR 1.15；95% CI 0.73 - 1.81）。女性发生轻度和重度低钠血症的风险在统计学上高于男性（分别为校正OR 1.36；95% CI 1.10 - 1.
