Hypertension in Africa Research Team (HART), North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
Cardiovascular Pathophysiology and Genomics Research Unit (CPGRU), University of the Witwatersrand, Johannesburg, South Africa.
Amino Acids. 2024 Aug 29;56(1):53. doi: 10.1007/s00726-024-03412-7.
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.
年轻时接触可改变的风险因素与过早发生致命和非致命的心血管和肾脏结局有关。尿代谢组学的应用显示出对肾功能和心血管疾病 (CVD) 的强大预测能力。因此，我们确定了在有和没有 CVD 风险因素的年轻成年人中，估计肾小球滤过率 (eGFR) 与尿代谢物之间的关联。纳入了显然健康的黑人和白人（年龄 20-30 岁），并根据是否存在以下风险因素进行分类，即肥胖、身体活动不足、吸烟、过量饮酒、隐匿性高血压、高血糖、血脂异常和低社会经济地位，形成 CVD 风险组 (N=1036)、CVD 风险群 (即存在 1 个 CVD 风险因素 (N=344)、2 个 CVD 风险因素 (N=360) 和 3+ CVD 风险因素 (N=332)) 和对照组 (N=166)。使用 CKD-EPI 方程计算 eGFR。使用液相色谱-串联质谱法进行靶向代谢组学分析，以测量氨基酸和酰基辅酶 A。与对照组相比，CVD 风险组、2 个 CVD 风险群和 3+ CVD 风险群的基于半胱氨酸蛋白酶抑制剂 C 的 eGFR 较低 (均 P≤0.033)。在 CVD 风险组中，eGFR 与组氨酸、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、异丁酰肉碱、戊酰肉碱和癸酰肉碱呈正相关 (均 P≤0.044)，在 CVD 风险群中也发现了类似的结果，特别是 2 个 CVD 风险群。eGFR 与与芳香族氨基酸和支链氨基酸代谢、能量代谢和氧化应激相关的代谢物呈正相关。这些发现可能表明在这个年轻的年龄没有既定的 CVD 的情况下，由于 CVD 风险因素的存在，这些代谢物的重吸收发生改变或代谢调节发生改变，以保护肾脏健康。
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