Thiazide-Associated Hyponatremia: A Retrospective Cohort Study Comparing Hydrochlorothiazide Versus Indapamide Versus Chlorthalidone

Abstract

Hyponatremia is a crucial complication of therapy with thiazide diuretics. This study compares the epidemiological and biochemical profiles and hospital course of patients using hydrochlorothiazide (HCTZ), indapamide (INDA), and chlorthalidone (CTD) admitted with thiazide-associated hyponatremia (TAH). Data were obtained retrospectively from the hospital's digital registries. The epidemiological and biochemical parameters between the HCTZ, INDA, and CTD groups were compared. The correlation between dose and biochemical parameters in each group was performed. The thiazide groups without diuretic co-medication were compared (HCTZ vs. INDA), and the correlation between dose and biochemical parameters in each group was examined. A comparison of the HCTZ (n = 135), INDA (n = 125), and CTD (n = 27) groups identified differences in serum potassium (s-K; p = 0.03). The hyponatremia correction rate was slower in the CTD group at 96 h after admission (p < 0.001). After the exclusion of diuretic co-medication, the HCTZ group (n = 64/135) showed a higher prevalence of ARBs, s-K (both p < 0.001), and a lower median (IQR) equipotent dose (12.5 (o) mg vs. 2.5 (1.2) mg), prevalence of ACE-I (p < 0.001), and eGFR (p = 0.03), when compared to the INDA group (n = 109/125). In conclusion, except for s-K, we observed no significant difference in biochemical and epidemiological profiles between HCTZ, INDA, and CTD. After excluding the influence of other diuretics, we observed higher s-K in the HCTZ group compared to the INDA group, potentially explained by the lower equipotent dose of HCTZ. The CTD group showed a statistically significant trend of slower hyponatremia correction.