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.
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.
Authors: A Tojo; W J Welch; V Bremer; M Kimoto; K Kimura; M Omata; T Ogawa; P Vallance; C S Wilcox Journal: Kidney Int Date: 1997-12 Impact factor: 10.612
Authors: Kristen L Jablonski; Jelena Klawitter; Michel Chonchol; Candace J Bassett; Matthew L Racine; Douglas R Seals Journal: Clin J Am Soc Nephrol Date: 2015-04-21 Impact factor: 8.237
Authors: Gesiane Tavares; Gabriela Venturini; Kallyandra Padilha; Roberto Zatz; Alexandre C Pereira; Ravi I Thadhani; Eugene P Rhee; Silvia M O Titan Journal: Metabolomics Date: 2018-02-27 Impact factor: 4.290
Authors: Jovia L Nierenberg; Jiang He; Changwei Li; Xiaoying Gu; Mengyao Shi; Alexander C Razavi; Xuenan Mi; Shengxu Li; Lydia A Bazzano; Amanda H Anderson; Hua He; Wei Chen; Jason M Kinchen; Casey M Rebholz; Josef Coresh; Andrew S Levey; Lesley A Inker; Michael Shlipak; Tanika N Kelly Journal: Metabolomics Date: 2019-11-13 Impact factor: 4.290
Authors: Eugene P Rhee; Clary B Clish; Anahita Ghorbani; Martin G Larson; Sammy Elmariah; Elizabeth McCabe; Qiong Yang; Susan Cheng; Kerry Pierce; Amy Deik; Amanda L Souza; Laurie Farrell; Carly Domos; Robert W Yeh; Igor Palacios; Kenneth Rosenfield; Ramachandran S Vasan; Jose C Florez; Thomas J Wang; Caroline S Fox; Robert E Gerszten Journal: J Am Soc Nephrol Date: 2013-05-16 Impact factor: 10.121