Risk factors of urinary tract infections with sodium-glucose cotransporter-2 inhibitors in heart failure

Abstract

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, while providing cardiorenal benefits in heart failure, have been associated with an elevated risk of urinary tract infections (UTIs). This study aimed to identify independent risk factors for UTIs in HF patients receiving SGLT-2 inhibitor therapy. In this multicenter retrospective cohort study, 110 heart failure patients treated with SGLT-2 inhibitors were included, among whom 41 developed UTIs. Comparative analyses between UTI and non-UTI groups were performed for demographic, clinical, and laboratory variables. Statistically significant factors (P < .05) in univariate logistic regression were subsequently entered into a multivariate model using backward stepwise elimination to adjust for potential confounders. Multivariate analysis identified 3 independent predictors of UTIs: female (odds ratio [OR] = 8.87, 95% confidence interval [CI]: 2.24-33.81; P = .002), elevated urinary ketones (OR = 10.59, 95% CI: 1.49, 75.44; P = .019), and prolonged bedridden status (OR = 46.96, 95% CI: 4.03, 547.35; P = .002). Notably, glycosuria severity did not significantly correlate with UTI risk in adjusted models. The identified risk factors - female, ketonuria, and immobility - challenge the conventional hypothesis linking SGLT-2 inhibitor-associated glycosuria to UTIs. Instead, these findings emphasize patient-specific vulnerabilities, particularly immune-metabolic dysregulation and functional decline, as primary drivers of infection risk. Clinicians should prioritize individualized monitoring strategies in high-risk subgroups to optimize therapeutic safety.

Keywords: heart failure; sodium-glucose cotransporter-2 inhibitors; urinary tract infections.

Figure 1.

Risk factors determined by logistic regression analysis. Multivariate logistic regression determined 3 independent risk factors, including gender (male) with odds of 0.115 (P = .002), increased urinary ketone with odds of 10.585 (P = .019), and long-term bedridden with odds of 46.961 (P = .002).