Kunutsor Setor K, Connelly Margery A, Bakker Stephan J L, Dullaart Robin P F
Section of Cardiology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, R2H 2A6, Canada.
, Labcorp, Morrisville, NC, USA.
Lipids Health Dis. 2025 Jul 19;24(1):245. doi: 10.1186/s12944-025-02668-6.
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.
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.
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.
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.
高密度脂蛋白胆固醇（HDL-C）、HDL颗粒浓度（HDL-P）以及HDL亚类与慢性肾脏病（CKD）发生发展之间的关系尚未得到充分阐明。本研究旨在探讨这些关联，并评估饮酒作为潜在混杂因素或效应修饰因素的作用。
对参与PREVEND队列研究的4179名个体（平均年龄：52岁；47.6%为男性）的数据进行分析。基线测量包括通过核磁共振波谱法定量的HDL-P及其亚组分（小、中、大），以及自我报告的酒精摄入量。根据KDIGO指南的标准定义新发CKD。使用Cox比例风险模型估计每增加1个标准差（SD）时各HDL指标的风险比（HRs）和95%置信区间（CIs）。
在中位随访8.3年期间，565名参与者发生了CKD。在调整包括饮酒在内的多个混杂因素后，HDL-P、中HDL和H3P与CKD风险呈适度负相关，调整后的HRs（95% CIs）分别为0.90（0.83 - 0.98）、0.91（0.83 - 1.00）和0.90（0.82 - 0.99）。相反，H7P与CKD风险呈正相关（HR 1.11，95% CI：1.00 - 1.22）。观察到中HDL、小HDL和H1P与性别存在显著交互作用。酒精摄入量既未显著改变这些关联，也未显示出与CKD风险的直接关系。
本研究提示HDL参数与CKD风险存在不同关联，以及这些参数与CKD风险关联中的性别差异。研究结果强调了HDL亚类的异质性以及未来研究中考虑性别特异性差异的必要性。饮酒对这些关联没有影响。
