Abstract
AIMSHyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition.METHODSOvid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken.RESULTSOne hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m−2. Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide.CONCLUSIONSPatients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required.
Highlights
Thiazide and thiazide-like diuretics, they differ in chemical structure, all inhibit the thiazide-sensitive sodium–chloride co-transporter, NCC, in the distal convoluted tubule of the kidney [1]
The main reasons for low quality scores were a lack of clearly stated inclusion and exclusion criteria, absence of documented patient consent and/or ethical approval, a lack of inclusion of patient perception, a lack of clarity regarding the name, dose and duration of thiazide therapy and whether thiazide-induced hyponatraemia patients represented a consecutive series treated consistently by the same physician(s) or at a single institution
Patients with thiazide-induced hyponatraemia were characterised by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia
Summary
Thiazide and thiazide-like diuretics, they differ in chemical structure, all inhibit the thiazide-sensitive sodium–chloride co-transporter, NCC, in the distal convoluted tubule of the kidney [1]. Since the demonstration of their anti-hypertensive effect in 1958 [2] they have been widely used in the management of hypertension, and continue to be so, notwithstanding their recent and controversial demotion to step 3 in UK hypertension guidance [3,4] Their benefits on all-cause mortality are equal to those of angiotensin-converting enzyme (ACE) inhibitors and calcium channel antagonists [5,6]. The mechanism of thiazide-induced hyponatraemia is poorly understood; mean serum sodium concentration in the total treated population is virtually unchanged by thiazide therapy [10], implying that thiazide-induced hyponatraemia occurs in a susceptible subgroup. This subgroup cannot be prospectively identified at present and so thiazide-induced hyponatraemia is largely unpredictable at the point of thiazide initiation. We set out to undertake a systematic review and meta-analysis of all thiazide-induced hyponatraemia reports published to date in order to summarise and reflect on current understanding of this condition
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