Plasma Metabolomic Profiles in Different Stages of CKD

Abstract

SummaryBackground 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.

Serum Metabolomic Profiling and Incident CKD among African Americans

“…For example, N-acetylalanine was negatively associated with eGFR CKD-EPI , having the lowest P value in this study, and Toyohara et al (19) reported N-acetylalanine to be a uremic retention anion. Another cross-sectional study of 30 participants, with 10 patients each in CKD stages 2-4, showed significant differences of plasma metabolites among various stages of CKD (20). In the study, 3-carboxy-4-methyl-5-propyl-2-furanpropanoate, a known uremic toxin, was higher in CKD stages 3 and 4 compared with CKD stage 2.…”

“…These technologies create an opportunity to investigate both the effect of kidney function on the metabolome and the ability of metabolomic measures to predict the onset of incident CKD (17). Several studies have shown that metabolic profiles can uncover potential biomarkers related to eGFR and different stages of CKD in multiple ethnicities (18)(19)(20)(21). A recent study has reported that adding metabolomic predictors of renal function independent of eGFR to clinical data may significantly improve the ability to predict onset of CKD among European Americans (17).…”

A Combined Epidemiologic and Metabolomic Approach Improves CKD Prediction

“…Increasing interest has been directed toward the application of metabolite profiling to plasma from individuals with existing CKD or ESRD. [2][3][4][30][31][32] Here, we profile plasma obtained from individuals up to 8 years before disease onset, on the principle that non-GFR markers of renal metabolite handling may be sensitive indicators of incipient kidney dysfunction. Although metabolite profiling alone may not be sufficiently specific to identify individuals who go on to develop CKD, it may contribute to clinical models of CKD prediction that contain other variables.…”

Renal Function and the Risk of Stroke and Bleeding in Patients With Atrial Fibrillation

“…Kidney dysfunction is associated with an increase in inflammatory and procoagulant biomarkers, including C-reactive protein, fibrinogen, factor VII, and factor VIII 13,14 and has been considered a marker of organ damage caused by hypertension or diabetes mellitus.…”