Abstract
The discovery of metabolomics-based biomarkers has been a focus of recent kidney dysfunction research. In the present study, we aimed to identify metabolites associated with chronic kidney disease (CKD) in the general population using a cross-sectional study design. At baseline, 6.5% of subjects had CKD. Pearson correlation analysis showed that 28 metabolites were significantly associated with estimated glomerular filtration rate (eGFR) after Bonferroni correction. Among these metabolites, 4 acylcarnitines, 12 amino acids, 4 biogenic amines, 1 phosphatidylcholine, and 1 sphingolipid were associated with CKD (p < 0.05). After eight years, 13.5% of subjects had CKD. Three amino acid metabolites were positively associated with new-onset CKD: citrulline [odds ratio (OR): 2.41, 95% confidence interval (CI): 1.26–4.59], kynurenine (OR: 1.98, 95% CI: 1.05–3.73), and phenylalanine (OR: 2.68, 95% CI: 1.00–7.16). The kynurenine:tryptophan ratio was also associated with CKD (OR: 3.20; 95% CI: 1.57–6.51). The addition of multiple metabolites significantly improved the CKD prediction by C statistics (0.756–0.85, p < 0.0001), and the net reclassification improvement was 0.84 (95% CI: 0.72–0.96). Elevated hs-C reactive protein (CRP) was associated with new-onset CKD (OR: 1.045, 95% CI: 1.005–1.086); however, this association disappeared following adjustment with the kynurenine:tryptophan ratio. The levels of citrulline and kynurenine and their ratio to tryptophan in CKD patients with proteinuria were worse than those with one or neither characteristic. Together, the results of this study demonstrate that amino acid metabolites are associated with CKD eight years after initial metabolite assessment. These results could improve the identification of subjects at high risk of CKD who have modified amino acid metabolism.
Highlights
More than 11% of the global population suffers from chronic kidney disease (CKD) [1]
Three amino acid metabolites were positively associated with new-onset CKD: citrulline [odds ratio (OR): 2.41, 95% confidence interval (CI): 1.26–4.59], kynurenine (OR: 1.98, 95% CI: 1.05–3.73), and phenylalanine (OR: 2.68, 95% CI: 1.00–7.16)
The proportion of subjects exhibiting current drinking was higher in the control group than the CKD group, whereas the prevalence of hypertension and diabetes was higher in the CKD group than the control group (p < 0.05)
Summary
More than 11% of the global population suffers from chronic kidney disease (CKD) [1]. CKD results in gradual loss of kidney function leading to end-stage renal disease, requiring dialysis or renal transplantation [2]. Early-stage CKD has few signs or symptoms, such that the disease is often not detected until the later stages; the risk of cardiovascular mortality and morbidity increases with CKD progression [3,4]. It is important to identify a predictive biomarker for CKD in the general population. CKD biomarker research has focused on metabolomics-based discovery. Recent studies of CKD have applied metabolite profiling to a longitudinal setting [8,9,10].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
