Abstract
Purpose of ReviewHypertension affects more than 30% of the world’s adult population and thiazide (and thiazide-like) diuretics are amongst the most widely used, effective, and least costly treatments available, with all-cause mortality benefits equivalent to angiotensin-converting enzyme inhibitors or calcium channel antagonists. A minority of patients develop thiazide-induced hyponatremia (TIH) and this is largely unpredictable at the point of thiazide prescription. In some cases, TIH can cause debilitating symptoms and require hospital admission. Although TIH affects only a minority of patients exposed to thiazides, the high prevalence of hypertension leads to TIH being the most common cause of drug-induced hyponatremia requiring hospital admission in the UK. This review examines current clinical and scientific understanding of TIH. Consideration is given to demographic associations, limitations of current electrolyte monitoring regimens, clinical presentation, the phenotype evident on routine clinical blood and urine tests as well as more extensive analyses of blood and urine in research settings, recent genetic associations with TIH, and thoughts on management of the condition.Recent FindingsRecent genetic and phenotyping analysis has suggested that prostaglandin E2 pathways in the collecting duct may have a role in the development of TIH in a subgroup of patients. Greater understanding of the molecular pathophysiology of TIH raises the prospect of pre-prescription TIH risk profiling and may offer novel insights into how TIH may be avoided, prevented and treated.SummaryThe rising prevalence of hypertension and the widespread use of thiazides mean that further understanding of TIH will continue to be a pressing issue for patients, physicians, and scientists alike for the foreseeable future.
Highlights
Summary of case report data0.08 to 0.34 diabetes mellitus, 19% with moderate renal impairment (eGFR 30–60 mL/min), and 6% with treated hypothyroidism [18]
Introduction to the Role ofThiazides in the Treatment of HypertensionHypertension is the most common modifiable cause of cardiovascular disease—the leading cause of mortality worldwide [1, 2]
The risk of developing thiazide-induced hyponatremia (TIH) is largely unpredictable at the point of thiazide initiation
Summary
0.08 to 0.34 diabetes mellitus, 19% with moderate renal impairment (eGFR 30–60 mL/min), and 6% with treated hypothyroidism [18]. The 2017 case series of hospitalized TIH patients broadly agreed with this polypharmacy data, with the most commonly co-prescribed medications being ACEi or ARB, non-thiazide diuretics, SSRIs (in 10%), aspirin, and NSAIDS [18]. Systematic review of the time to TIH found that clinical presentation with TIH occurred a mean of 19 (95% CI 8–30) days after starting treatment [17]. This makes it difficult to determine what the optimal timing of a single post-thiazide initiation blood test for serum urea and electrolytes (U&E) should be. The 2017 case series of hospitalized TIH patients broadly agreed with this with serum sodium 122 ± 0.6 mM, potassium 3.7 ± 0.06 mM and reduced osmolality of 255 ± 4 mOsm/kg [18]
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