Sex Differences in Electrolyte Disturbances Among Diuretic Users According to Renal Function and Age

Diuretics are widely used in Japan for the treatment of hypertension and heart failure. Electrolyte disturbance is a common adverse reaction to diuretics and may be life-threatening. Previous studies have shown that diuretic-induced electrolyte disturbance is more common in women. Electrolyte balance is regulated by the kidneys, and renal function tends to decline with advancing age.

The aim of this study was to identify patients at high risk of adverse reactions to diuretics, considering the effects of sex, renal function, and age on susceptibility to diuretic-induced electrolyte disturbance.

Claims data for 67,135 patients on diuretics in Japan were sourced from DeSC Healthcare, Inc. The data covered the period from April 2020 to March 2021.

Analysis of patient numbers using the chi-squared test showed that hyperkalemia was more common in men than in women (326 vs. 271; p = 0.003) and that hypokalemia was more common in women than in men (413 vs. 285; p < 0.001). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for women considering age and renal function (estimated glomerular filtration rate [eGFR]). In elderly patients aged ≥ 75 years, the odds of developing hypokalemia in women compared to men were 1.47 (95% CI 1.13-1.91) for eGFR 60-30 mL/min/1.73 m² and 2.05 (95% CI 1.08-4.10) for eGFR < 30 mL/min/1.73 m².

Among women aged ≥ 75 years, those in lower eGFR groups (60-30 and < 30) had higher odds of hypokalemia compared to men. These data highlight the importance of monitoring for adverse reactions to diuretics, particularly hypokalemia, in elderly women with low eGFR.