Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Am J Kidney Dis. 2013 Jul;62(1):67-72. doi: 10.1053/j.ajkd.2013.02.365. Epub 2013 Apr 18.
Hyponatremia is one of the most common adverse reactions to thiazide diuretics. In the present study, we analyzed differences in thiazide-associated hyponatremia between men and women and between different categories of age, body mass index (BMI), daily thiazide dose, and estimated glomerular filtration rate.
Population-based cohort study.
SETTING & PARTICIPANTS: 13,325 individuals 45 years and older living in a suburb of Rotterdam, as part of the Rotterdam Study.
Exposure to thiazide diuretics.
The association between thiazide exposure and hyponatremia (defined as sodium level ≤135 mmol/L; mild hyponatremia, 130-≤135 mmol/L; moderate, >125-<130 mmol/L; and severe, ≤125 mmol/L) was studied in a period covering more than 10 years using Cox proportional hazard regression analyses.
718 participants used thiazides at baseline, and 2,738 participants started on thiazide therapy during follow-up. 522 participants developed hyponatremia, of whom 32.4% were exposed to thiazide diuretics at the time of hyponatremia. Thiazide exposure was associated with an almost 5 times higher risk of hyponatremia than no exposure (HR, 4.95; 95% CI, 4.12-5.96). The risk of mild hyponatremia was more than 4.5 times higher in thiazide-exposed individuals; risks of moderate and severe hyponatremia were both 8 times higher in individuals exposed to thiazides. Age and BMI (but not sex [P = 0.8] or estimated glomerular filtration rate [P = 0.2]) significantly modified this risk of thiazide-associated hyponatremia (P < 0.05).
Some cases of severe hyponatremia may have been missed if patients were admitted to the hospital without assessment of serum sodium in the general practitioner's laboratory. Nonproportionality of hazards in the first period was explained as possible "depletion of susceptibles" in this closed cohort.
Thiazide use is associated with a substantially increased risk of hyponatremia. Age and BMI significantly influenced the thiazide-associated risk of hyponatremia.
低钠血症是噻嗪类利尿剂最常见的不良反应之一。本研究分析了男性和女性之间以及不同年龄、体重指数（BMI）、噻嗪类药物日剂量和估计肾小球滤过率类别之间噻嗪类药物相关低钠血症的差异。
基于人群的队列研究。
13325 名年龄在 45 岁及以上的居住在鹿特丹郊区的个体，作为鹿特丹研究的一部分。
噻嗪类药物暴露。
使用 Cox 比例风险回归分析，在超过 10 年的时间内研究了噻嗪类药物暴露与低钠血症（定义为血清钠水平≤135mmol/L；轻度低钠血症，130-≤135mmol/L；中度，>125-<130mmol/L；重度，≤125mmol/L）之间的关系。
718 名参与者在基线时使用噻嗪类药物，2738 名参与者在随访期间开始使用噻嗪类药物治疗。522 名参与者发生低钠血症，其中 32.4%在低钠血症时暴露于噻嗪类利尿剂。与无暴露相比，噻嗪类药物暴露与低钠血症的风险几乎高出 5 倍（HR，4.95；95%CI，4.12-5.96）。噻嗪类药物暴露者发生轻度低钠血症的风险高出 4.5 倍以上；暴露于噻嗪类药物的个体发生中度和重度低钠血症的风险均高出 8 倍。年龄和 BMI（但不是性别[P=0.8]或估计肾小球滤过率[P=0.2]）显著改变了噻嗪类药物相关低钠血症的风险（P<0.05）。
如果患者在全科医生实验室就诊时未评估血清钠，可能会漏诊一些严重低钠血症的病例。该闭合队列中，最初时间段的危害不成比例，这可以解释为可能存在“易感人群的枯竭”。
噻嗪类药物的使用与低钠血症的风险显著增加相关。年龄和 BMI 显著影响噻嗪类药物相关低钠血症的风险。
