High-density lipoprotein cholesterol, particles and subspecies and the risk of chronic kidney disease: The PREVEND prospective study.

Background: The relationships between high-density lipoprotein cholesterol (HDL-C), HDL particle concentration (HDL-P), and HDL subspecies with the development of chronic kidney disease (CKD) have not been well characterized. This study aimed to examine these associations and evaluate the role of alcohol consumption as a potential confounder or effect modifier.

Methods: Data was analyzed from 4,179 individuals (mean age: 52 years; 47.6% male) participating in the PREVEND cohort. Baseline measurements included HDL-P and its subfractions (small, medium, and large), quantified by nuclear magnetic resonance spectroscopy, and self-reported alcohol intake. Incident CKD was defined using criteria from the KDIGO guidelines. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for each HDL metric per 1 standard deviation (SD) increment.

Results: Over a median follow-up of 8.3 years, 565 participants developed CKD. After adjusting for multiple confounders, including alcohol use, HDL-P, medium HDL, and H3P showed modest inverse associations with CKD risk, with adjusted HRs (95% CIs) of 0.90 (0.83-0.98), 0.91 (0.83-1.00), and 0.90 (0.82-0.99), respectively. Conversely, H7P was positively associated with CKD risk (HR 1.11, 95% CI: 1.00-1.22). Significant interactions with sex were observed for medium HDL, small HDL, and H1P. Alcohol intake neither significantly modified the associations nor showed a direct relationship with CKD risk.

Conclusions: This study suggests distinct associations of HDL parameters with CKD risk as well as sex differences in the associations of these parameters with CKD risk. The findings underscore the heterogeneity of HDL subspecies and the need to consider sex-specific differences in future studies. Alcohol consumption had no impact on these associations.