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高血压人群中与正常白蛋白尿状况相关的差异代谢谱。

Differential metabolic profile associated with the condition of normoalbuminuria in the hypertensive population.

机构信息

Laboratorio de Inmunoalergia y Proteómica, Departamento de Inmunología, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, España.

Laboratorio Traslacional Cardiorrenal, Instituto de Investigación I+12 Hospital Universitario 12 de Octubre/CIBER-CV, Madrid; Departamento de Fisiopatología Vascular, Hospital Nacional de Parapléjicos, SESCAM , Toledo, España.

出版信息

Nefrologia (Engl Ed). 2020 Jul-Aug;40(4):440-445. doi: 10.1016/j.nefro.2019.10.007. Epub 2020 Mar 3.

Abstract

BACKGROUND AND AIM

Albuminuria is an indicator of sub-clinical organ damage and a marker of cardiovascular risk and renal disease. A percentage of hypertensive patients develop albuminuria despite being under chronic suppression of the renin-angiotensin system (RAS). We previously identified urinary metabolites associated with the development of albuminuria. In this study, we searched for metabolic alterations which reflect different levels within the condition of normoalbuminuria.

PATIENTS, MATERIALS AND METHODS: Urine from 48 hypertensive patients under chronic RAS suppression was analysed. They were classified according to the albumin/creatinine ratio (ACR) into 3groups: Normoalbuminuria (<10mg/g); high-normal (10-30mg/g in men, or 20-40mg/g in women); and moderately high albuminuria (microalbuminuria, 30-200mg/g or 40-300mg/g, respectively). The metabolome was analysed by mass spectrometry and a correlation analysis was performed between altered metabolite levels and ACR.

RESULTS

Oxaloacetate, 3-ureidopropionate, guanidoacetate and malate show significant variation between the normo and micro groups. Additionally, these metabolites are able to differentiate between patients in the normo and high-normal range. A significant correlation between metabolites and ACR was found. Observed variations point to alterations in the energy metabolism already in patients with albuminuria in the high-normal range.

CONCLUSIONS

The association between the molecular panel consisting of 3-ureidopropionate, oxaloacetate, malate and guanidoacetate and different levels of albuminuria is confirmed. A metabolic fingerprint was also identified showing variations within the condition of normoalbuminuria allowing an earlier molecular stratification of patients.

摘要

背景与目的

蛋白尿是亚临床器官损伤的指标,也是心血管风险和肾脏疾病的标志物。尽管肾素-血管紧张素系统(RAS)受到慢性抑制,仍有一部分高血压患者会出现蛋白尿。我们之前已经确定了与蛋白尿发展相关的尿代谢物。在这项研究中,我们寻找反映正常白蛋白尿状态下不同水平的代谢变化。

患者、材料和方法:分析了 48 名接受慢性 RAS 抑制的高血压患者的尿液。根据白蛋白/肌酐比值(ACR)将他们分为 3 组:正常白蛋白尿(<10mg/g);高正常(男性 10-30mg/g,女性 20-40mg/g);中度高白蛋白尿(微量白蛋白尿,分别为 30-200mg/g 或 40-300mg/g)。通过质谱分析代谢组学,并对改变的代谢物水平与 ACR 之间进行相关性分析。

结果

草酰乙酸、3-脲丙酸、胍基乙酸和苹果酸在正常组和微量组之间显示出显著差异。此外,这些代谢物能够区分正常和高正常范围内的患者。代谢物与 ACR 之间存在显著相关性。观察到的变化表明,在高正常范围内的白蛋白尿患者中,能量代谢已经发生了改变。

结论

由 3-脲丙酸、草酰乙酸、苹果酸和胍基乙酸组成的分子谱与不同水平的白蛋白尿之间的关联得到了证实。还确定了一个代谢指纹,显示了正常白蛋白尿状态下的变化,从而能够更早地对患者进行分子分层。

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