年轻时暴露于可改变的危险因素与过早致命和非致命的心血管和肾脏结局有关。尿代谢组学的使用显示了肾功能和心血管疾病(CVD)的强大可预测性。因此,我们确定了有或没有CVD危险因素的年轻人的肾小球滤过率(eGFR)与尿代谢物之间的关联。包括明显健康的黑白性别(20-30岁),并根据是否存在风险因素进行分类,即,肥胖,缺乏身体活动,吸烟,过量饮酒,隐性高血压,高血糖症,血脂异常和低社会经济地位,形成CVD风险组(N=1036),CVD风险集群(即具有1个CVD风险因素(N=344),2个CVD危险因素(N=360)和3+CVD危险因素(N=332)和对照组(N=166)。用CKD-EPI方程计算eGFR。使用液相色谱-串联质谱的靶向代谢组学方法用于测量氨基酸和酰基肉碱。在CVD风险组中,基于胱抑素C的eGFR较低,与对照组相比,2和3+CVD风险集群(所有P≤0.033)。在CVD风险组中,eGFR与组氨酸呈正相关,赖氨酸,天冬酰胺,甘氨酸,丝氨酸,谷氨酰胺,二甲基甘氨酸,苏氨酸,丙氨酸,肌酸,胱氨酸,蛋氨酸,酪氨酸,焦谷氨酸,亮氨酸/异亮氨酸,天冬氨酸,色氨酸,谷氨酸,游离肉碱,乙酰肉碱,丙酰肉碱,异戊酰基肉碱,辛酰肉碱和癸酰肉碱(均P≤0.044),在心血管疾病风险集群中发现了类似的结果,特别是2心血管疾病风险集群。eGFR与芳香族氨基酸和支链氨基酸代谢相关的代谢物呈正相关,能量代谢和氧化应激。这些发现可能表明这些代谢物的重吸收改变或代谢调节改变,以保持肾脏健康的CVD危险因素在这个年轻的年龄没有确定的CVD。
The exposure to modifiable risk factors at young ages have been linked to premature fatal and non-fatal cardiovascular and kidney outcomes. The use of urinary metabolomics has shown strong predictability of kidney function and cardiovascular disease (CVD). We therefore determined the associations between estimated glomerular filtration rate (eGFR) and urinary metabolites in young adults with and without CVD risk factors. Apparently healthy Black and White sexes were included (aged 20-30 years) and categorised by the presence or absence of risk factors, i.e., obesity, physical inactivity, smoking, excessive alcohol intake, masked hypertension, hyperglycemia, dyslipidemia and low socio-economic status, forming the CVD risk group (N = 1036), CVD risk clusters (i.e. presenting with 1 CVD risk factor (N = 344), 2 CVD risk factors (N = 360) and 3 + CVD risk factors (N = 332)) and the control group (N = 166). eGFR was calculated with CKD-EPI equations. A targeted metabolomics approach using liquid chromatography-tandem mass spectrometry was used to measure amino acids and acylcarnitines. Lower cystatin C-based eGFR were indicated in the CVD risk group, 2 and 3 + CVD risk clusters compared to the control group (all P ≤ 0.033). In the CVD risk group, eGFR associated positively with histidine, lysine, asparagine, glycine, serine, glutamine, dimethylglycine, threonine, alanine, creatine, cystine, methionine, tyrosine, pyroglutamic acid, leucine/isoleucine, aspartic acid, tryptophan, glutamic acid, free carnitine, acetylcarnitine, propionylcarnitine, isovalerylcarnitine, octanoylcarnitine and decanoylcarnitine (all P ≤ 0.044), with similar results found in the CVD risk clusters, particularly the 2 CVD risk cluster. eGFR was positively associated with metabolites linked to aromatic amino acid and branched-chain amino acid metabolism, energy metabolism and oxidative stress. These findings may indicate altered reabsorption of these metabolites or altered metabolic regulation to preserve renal health in the setting of CVD risk factors at this young age without established CVD.