慢性肾脏病中的高密度脂蛋白脂质组学。
High-Density Lipoprotein Lipidomics in Chronic Kidney Disease.
机构信息
Department of Medicine, University of Washington, Seattle, USA.
Department of Laboratory Medicine & Pathology, University of Washington, Seattle, USA.
出版信息
Clin Chem. 2023 Mar 1;69(3):273-282. doi: 10.1093/clinchem/hvac216.
BACKGROUND
Patients with chronic kidney disease (CKD) have dysfunctional high-density lipoprotein (HDL) particles as compared with the general population. Understanding the lipid composition of HDL may provide mechanistic insight. We tested associations of estimated glomerular filtration rate (eGFR) and albuminuria with relative HDL abundance of ceramides, sphingomyelins, and phosphatidylcholines in participants with CKD.
METHODS
We studied 490 participants with CKD from the Seattle Kidney Study. HDL was isolated from plasma; targeted lipidomics was used to quantify the relative abundance of ceramides, sphingomyelins, and phosphatidylcholines per 10 µg of total HDL protein. We evaluated the associations of eGFR and albuminuria with levels of individual lipids and lipid classes (including 7 ceramides, 6 sphingomyelins, and 24 phosphatidylcholines) using multivariable linear regression, controlling for multiple comparisons via the false discovery rate.
RESULTS
The mean (SD) eGFR was 45 (24) mL/min/1.73 m2; the median (IQR[interquartile range]) albuminuria was 108 (16, 686) mg/g (12.2 [1.8, 77.6] mg/mmol) urine creatinine. After adjusting for demographics, past medical history, laboratory values, and medication use, eGFR was not associated with higher relative abundance of any class of lipids or individual lipids. Greater albuminuria was significantly associated with a higher relative abundance of total ceramides and moderate-long R-chain sphingomyelins, ceramides 22:0 and 24:1, hexosylceramide 16:0, sphingomyelin 16:0, and phosphatidylcholines 29:0, 30:1, and 38:2; the strongest association was for hexosylceramide 16:0 (increase per doubling of urine albumin to creatinine ratio 0.022 (95% CI, 0.012-0.032).
CONCLUSIONS
Greater albuminuria was significantly associated with specific alterations in the lipid composition of HDL in participants with CKD.
背景
与普通人群相比，慢性肾脏病（CKD）患者的高密度脂蛋白（HDL）颗粒功能失调。了解 HDL 的脂质组成可能提供机制上的见解。我们检测了 CKD 患者估算肾小球滤过率（eGFR）和白蛋白尿与 HDL 中神经酰胺、鞘磷脂和磷脂酰胆碱相对丰度的相关性。
方法
我们研究了西雅图肾脏病研究中的 490 名 CKD 患者。从血浆中分离 HDL；使用靶向脂质组学来定量每 10µg 总 HDL 蛋白中神经酰胺、鞘磷脂和磷脂酰胆碱的相对丰度。我们使用多变量线性回归评估 eGFR 和白蛋白尿与个体脂质和脂质类别的水平（包括 7 种神经酰胺、6 种鞘磷脂和 24 种磷脂酰胆碱）之间的相关性，通过错误发现率对多变量比较进行控制。
结果
平均（SD）eGFR 为 45（24）mL/min/1.73 m2；中位数（IQR[四分位间距]）白蛋白尿为 108（16，686）mg/g（12.2[1.8，77.6]mg/mmol）尿肌酐。调整人口统计学、既往病史、实验室值和药物使用后，eGFR 与任何脂质类别的相对丰度或个体脂质均无相关性。白蛋白尿较多与总神经酰胺和中等长链鞘磷脂、神经酰胺 22:0 和 24:1、己糖神经酰胺 16:0、鞘磷脂 16:0 和磷脂酰胆碱 29:0、30:1 和 38:2 的相对丰度较高显著相关；与尿白蛋白与肌酐比值每增加一倍，己糖神经酰胺 16:0 的增加幅度最大（0.022（95%CI，0.012-0.032）。
结论
在 CKD 患者中，白蛋白尿较多与 HDL 脂质组成的特定变化显著相关。
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