Feng Qian, Li Yuanmeng, Yang Yuwei, Feng Jiafu
College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Department of Medical Laboratory, Affiliated Hospital of Southwest Medical University, Luzhou, China.
Front Physiol. 2020 Oct 6;11:578799. doi: 10.3389/fphys.2020.578799. eCollection 2020.
Diabetic kidney disease (DKD) leads to low high albuminuria and gradually progresses to very high albuminuria with kidney insufficiency. However, about 20-40% of DKD is normoalbuminuric DKD (NADKD), which has impaired kidney function but normal urine albumin. This study is to investigate the urine metabolomic profiles of patients with NADKD and albuminuria DKD (ADKD).
In total, 95 patients were divided into a simple diabetes mellitus group (SDM group), an ADKD group, and a NADKD group. All subjects were analyzed for urine metabolites using non-targeted metabolomics based on ultra-performance liquid chromatography - tandem mass spectrometry.
The urine metabolomic profiles of the SDM group, NADKD group, and ADKD group were significantly different, and 65 different metabolites were identified among the three groups. Metabolic pathway analysis of these differential metabolites found that the top three significantly changed metabolic pathways were linoleic acid metabolism, citrate cycle, and, arginine and proline metabolism. There are 12 metabolites enriched in these three metabolic pathways. In detail, compared with those in the SDM group, the levels of γ-linolenic acid in the ADKD group were increased significantly, while the levels of succinic acid, -aconitic acid, citric acid, L-proline, L-erythro-4-hydroxyglutamate, -methylhydantoin, -carbamoylputrescine, spermidine, and 5-aminopentanoic acid were reduced significantly; compared with those in the NADKD group, the levels of linoleic acid, γ-linolenic acid, and L-malic acid in the ADKD group were increased significantly ( < 0.05), while the levels of L-proline, L-erythro-4-hydroxyglutamate, -carbamoylputrescine, and spermidine were significantly reduced ( < 0.05). However, there were no significant difference between the SDM group and NADKD group ( > 0.05).
The urine metabolomic profiles between the NADKD group and the ADKD group are significantly different. Specifically, these two groups have distinct levels of linoleic acid, γ-linolenic acid, L-malic acid, L-proline, L-erythro-4-hydroxyglutamate, -carbamoylputrescine, and spermidine.
糖尿病肾病（DKD）会导致低白蛋白尿，并逐渐发展为伴有肾功能不全的高白蛋白尿。然而，约20%-40%的DKD为正常白蛋白尿性糖尿病肾病（NADKD），其肾功能受损但尿白蛋白正常。本研究旨在调查NADKD患者和白蛋白尿性糖尿病肾病（ADKD）患者的尿液代谢组学特征。
总共95例患者被分为单纯糖尿病组（SDM组）、ADKD组和NADKD组。所有受试者均采用基于超高效液相色谱-串联质谱的非靶向代谢组学方法分析尿液代谢物。
SDM组、NADKD组和ADKD组的尿液代谢组学特征存在显著差异，三组之间共鉴定出65种不同的代谢物。对这些差异代谢物的代谢途径分析发现，变化最显著的前三条代谢途径为亚油酸代谢、柠檬酸循环以及精氨酸和脯氨酸代谢。这三条代谢途径中有12种代谢物富集。具体而言，与SDM组相比，ADKD组中γ-亚麻酸水平显著升高，而琥珀酸、顺乌头酸、柠檬酸、L-脯氨酸、L-赤藓糖-4-羟基谷氨酸、N-甲基乙内酰脲、N-氨甲酰腐胺、亚精胺和5-氨基戊酸水平显著降低；与NADKD组相比，ADKD组中亚油酸、γ-亚麻酸和L-苹果酸水平显著升高（P<0.05），而L-脯氨酸、L-赤藓糖-4-羟基谷氨酸、N-氨甲酰腐胺和亚精胺水平显著降低（P<0.05）。然而，SDM组和NADKD组之间无显著差异（P>0.05）。
NADKD组和ADKD组之间的尿液代谢组学特征存在显著差异。具体而言，这两组在亚油酸、γ-亚麻酸、L-苹果酸、L-脯氨酸、L-赤藓糖-4-羟基谷氨酸、N-氨甲酰腐胺和亚精胺水平上存在明显差异。
