Mahasti Emami Hamzehkolaee , Amirhesam Alirezaei, Marjan Moudi, Sepide Veysi , Masoumeh Asgharpour,
Volume 83, Issue 2 (5-2025)
Background: Hydrochlorothiazide (HCTZ) is widely used for hypertension, but electrolyte disorders-especially hyponatremia remain major safety concerns. Limited regional data on its prevalence, timing, and determinants may undermine patient safety. This retrospective study evaluated risk factors for HCTZ-associated hyponatremia in hospitalized adults with hypertension and identified predictors of its severity.
Methods: A retrospective analysis was conducted on 217 patients hospitalized at Ayatollah Rouhani Hospital in Babol (2019-2021). Eligible participants were aged ≥18 years and had received HCTZ for at least seven consecutive days. Patients with baseline hyponatremia, concurrent use of drugs independently causing hyponatremia, or incomplete laboratory data were excluded. Demographic, clinical, medication, and biochemical variables were abstracted from medical records. Hyponatremia was defined as serum sodium <135 mmol/L and categorized as mild (130-134), moderate (125-129), or severe (<125). Predictors of occurrence were estimated with multivariable logistic regression; onset timing was assessed using a Cox proportional hazards model; and severity determinants were examined through multinomial logistic regression. Statistical significance was set at P<0.05.
Results: Hyponatremia occurred in 32.7% (71.217) of patients, most frequently within the early weeks of HCTZ treatment. Among affected individuals, 49.3% had mild, 31.0% moderate, and 19.7% severe hyponatremia. Adjusted analyses showed that older age, concurrent nonsteroidal anti-inflammatory drug (NSAID) use, shorter HCTZ duration, and lower serum potassium and uric acid independently increased hyponatremia risk, while HCTZ dose and sex were nonsignificant. In the Cox model, older age and lower potassium and uric acid predicted earlier onset. Patients with hyponatremia more often presented with weakness, headache, altered consciousness, and seizures. Baseline glucose, creatinine, and most comorbidities were not independently associated with risk or timing.
Conclusion: HCTZ-related hyponatremia was common and typically emerged soon after initiation. Advanced age, NSAID co-administration, brief exposure, and reduced potassium and uric acid were practical, readily measurable markers associated with both occurrence and earlier onset. Routine early and repeated electrolyte monitoring particularly in older adults and patients receiving NSAIDs- together with patient education on warning symptoms is recommended. These findings highlight key predictors for targeted surveillance and prevention in similar clinical contexts.
