Early hyponatremia after starting thiazide associated with increased mortality risk
Key takeaways:
- Mortality risk nearly doubled for patients who developed hyponatremia soon after initiating a thiazide vs. controls.
- Patients with early hyponatremia also had increased risks for complications, including sepsis.
Patients who develop early hyponatremia after starting thiazide diuretics have a higher mortality risk than those with normal sodium levels, according to retrospective study data.
“Hyponatremia is a common complication of thiazide therapy because thiazide diuretics impair the ability of the kidney to dilute the urine but not the ability to concentrate the urine,” Steven G. Achinger, MD, a nephrologist at the University of South Florida Department of Nephrology and Hypertension in Tampa, Florida, wrote with colleagues. “Thiazide diuretics have been found to lead to sudden complications, such as hyponatremic encephalopathy, which is associated with severe neurological manifestations and possibly death. Currently, there are no studies in the literature that address whether or not thiazide-associated hyponatremia (135 mmol/L) is linked to increased mortality when compared with patients on thiazides who do not become hyponatremic.”
Researchers set out to compare mortality between outpatients who developed early hyponatremia after starting a thiazide diuretic and those who did not develop the condition. The cohort study used data from the TriNetX federated health research network, including electronic medical records of approximately 93 million patients across 76 U.S. health care organizations. The cohort included patients aged 40 to 90 years with essential hypertension who started a thiazide from 2010 and 2021.
After propensity score matching, there were 22,052 patients in each cohort. The hyponatremia group developed early hyponatremia, defined as a serum sodium of 135 mmol/L or lower within 6 months after starting thiazide, vs. controls who had a serum sodium level between 136 mmol/L and 144 mmol/L after thiazide initiation.
Primary outcome of the study was 1-year mortality.
Patients in the hyponatremia cohort had a higher mortality risk than controls at any time during the study (HR = 1.96; 95% CI, 1.72-2.28), according to the researchers.
In addition, patients who developed early hyponatremia were also at increased risk for health complications, including sepsis, pneumonia, urinary tract infection, cellulitis, myocardial infarction, stroke, congestive heart failure, ataxia and hip fracture.
“It is likely that 3.6 million patients taking thiazide diuretics in the United States may be at elevated mortality risk,” the researchers wrote. The results “argue for increased efforts at educating patients about fluid intake during thiazide diuretic therapy and for steps to be taken to identify patients at risk very early on through monitoring of the body weight and to closely monitor the serum electrolytes in patients on thiazides diuretic and to intervene early when patients with a serum sodium of [no more than] 135mmol/L are identified.”
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