Dataset Information

Plasma metabolomic profiles in different stages of CKD.

ABSTRACT:

Background and objectives

CKD is a common public health problem. Identifying biomarkers adds prognostic/diagnostic value by contributing to an understanding of CKD at the molecular level and possibly defining new drug targets. Metabolomics provides a snapshot of biochemical events at a particular time in the progression of CKD. This cross-sectional metabolomics study ascertained whether plasma metabolite profiles are significantly different in CKD stages 2, 3, and 4.

Design, setting, participants, & measurements

An analysis of plasma metabolites, using gas and liquid chromatography coupled to mass spectrometry, was conducted on 30 nondiabetic men ages 40-52 years, with 10 participants each in CKD stages 2, 3, and 4 based on their estimated GFR (calculated by the Modified Diet in Renal Disease formula). Participants were recruited in late 2008, and plasma samples were tested at Metabolon Inc and analyzed in 2012.

Results

Comparison of stage 3/stage 2 identified 62 metabolites that differed (P ≤ 0.05), with 39 higher and 23 lower in stage 3 compared with stage 2; comparisons of stage 4/stage 2 identified 111 metabolites, with 66 higher and 45 lower; and comparisons of stage 4/stage 3 identified 11 metabolites, with 7 higher and 4 lower. Major differences in metabolite profiles with increasing stage of CKD were observed, including altered arginine metabolism, elevated coagulation/inflammation, impaired carboxylate anion transport, and decreased adrenal steroid hormone production.

Conclusions

Global metabolite profiling of plasma uncovered potential biomarkers of stages of CKD. Moreover, these biomarkers provide insight into possible pathophysiologic processes that may contribute to progression of CKD.

SUBMITTER: Shah VO

PROVIDER: S-EPMC3586968 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and Aims: Studies of both animals and humans show that a high intake of vitamin A is associated with a lower risk of dyslipidemia. However, an association of plasma retinol levels with dyslipidemia is unclear. Therefore, the aim of this study is to investigate an association between plasma retinol and dyslipidemia and to identify related metabolites and pathways in the general population. Methods: We included 250 participants aged 20-80 years from the Wellness Living Laboratory (WELL) China cohort. Associations between plasma retinol levels and dyslipidemia were analyzed using adjusted logistic models. Related metabolites were identified using ANCOVA, adjusted for the false discovery rate (FDR) and used for pathway analyses. Because there are sex differences in plasma retinol levels, all analyses were conducted separately by sex. Results: Plasma retinol was significantly higher in men than in women. A positive association between plasma retinol and dyslipidemia was found in both sexes. In men, the 2nd and 3rd tertiles showed significantly higher proportions of dyslipidemia than the 1st tertile (1st tertile vs. 2nd tertile: p = 0.026; 1st tertile vs. 3rd tertile: p = 0.003). In women, the 3rd tertile showed a significantly higher proportion of dyslipidemia than the 1st and 2nd tertile (3rd tertile vs. 1st tertile: p = 0.002, 3rd tertile vs. 2nd tertile: p = 0.002). Overall, 75 and 30 metabolites were significantly associated with retinol levels in men and women, respectively. According to these metabolites, lipid metabolic pathways, including glycerophospholipid, arachidonic acid, linoleic acid, alpha-linolenic acid, and glycosylphosphatidylinositol (GPI), as well as steroid hormone biosynthesis pathways were found to overlap across the sexes. These pathways showed that elevated retinol levels might be associated with hormone metabolism and inflammation status. Conclusions: We found a positive association between plasma retinol levels and dyslipidemia. Related metabolomic profiles and interrupted pathways showed that such an increase might be associated with steroid hormone synthesis and inflammation. In addition, large, population-based longitudinal studies and intervention studies are needed to confirm the role of retinol in lipid metabolism and the prevention of cardiovascular disease (CVD).