Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, BE-3000 Leuven, Belgium.
Toxins (Basel). 2022 Jun 16;14(6):412. doi: 10.3390/toxins14060412.
Patients with kidney failure (KF) have a high incidence of cardiovascular (CV) disease, partly driven by insufficient clearance of uremic toxins. Recent investigations have questioned the accepted effects of adverse lipid profile and CV risk in uremic patients. Therefore, we related a panel of uremic toxins previously associated with CV morbidity/mortality to a full lipid profile in a large, tri-national, cross-sectional cohort. Total, high-density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL), and remnant cholesterol, as well as triglyceride, levels were associated with five uremic toxins in a cohort of 611 adult KF patients with adjustment for clinically relevant covariates and other patient-level variables. Univariate analyses revealed negative correlations of total, non-HDL, and LDL cholesterol with all investigated uremic toxins. Multivariate linear regression analyses confirmed independent, negative associations of phenylacetylglutamine with total, non-HDL, and LDL cholesterol, while indole-3 acetic acid associated with non-HDL and LDL cholesterol. Furthermore, trimethylamine-N-Oxide was independently and negatively associated with non-HDL cholesterol. Sensitivity analyses largely confirmed findings in the entire cohort. In conclusion, significant inverse associations between lipid profile and distinct uremic toxins in KF highlight the complexity of the uremic milieu, suggesting that not all uremic toxin interactions with conventional CV risk markers may be pathogenic.
肾衰竭(KF)患者心血管(CV)疾病的发病率很高,部分原因是尿毒症毒素的清除不足。最近的研究质疑了不良血脂谱和尿毒症患者 CV 风险的公认影响。因此,我们在一个大型的、三国、横断面队列中,将先前与 CV 发病率/死亡率相关的一组尿毒症毒素与完整的血脂谱相关联。在 611 名成年 KF 患者的队列中,调整了临床相关协变量和其他患者水平变量后,总胆固醇、高密度脂蛋白(HDL)、非高密度脂蛋白、低密度脂蛋白(LDL)和残胆固醇以及甘油三酯水平与五种尿毒症毒素相关。单变量分析显示,总胆固醇、非高密度脂蛋白和 LDL 胆固醇与所有研究的尿毒症毒素呈负相关。多元线性回归分析证实,苯乙酰谷氨酰胺与总胆固醇、非高密度脂蛋白和 LDL 胆固醇呈独立、负相关,而吲哚-3 乙酸与非高密度脂蛋白和 LDL 胆固醇相关。此外,三甲胺 N-氧化物与非高密度脂蛋白胆固醇呈独立、负相关。敏感性分析在整个队列中基本证实了这些发现。总之,KF 患者的血脂谱与特定尿毒症毒素之间存在显著的负相关,突出了尿毒症环境的复杂性,表明并非所有尿毒症毒素与传统 CV 风险标志物的相互作用都具有致病性。