1H NMR-based metabolite profiling of plasma in a rat model of chronic kidney disease.
Chronic kidney disease (CKD) is characterized by the gradual loss of the kidney function to excrete wastes and fluids from the blood. (1)H NMR-based metabolomics was exploited to investigate the altered metabolic pattern in rats with CKD induced by surgical reduction of the renal mass (i.e., 5/6 nephrectomy (5/6 Nx)), particularly for identifying specific metabolic biomarkers associated with early of CKD. Plasma metabolite profiling was performed in CKD rats (at 4- or 8-weeks after 5/6 Nx) compared to sham-operated rats. Principle components analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) score plots showed a significant separation between the groups. The resulting metabolic profiles demonstrated significantly increased plasma levels of organic anions, including citrate, β-hydroxybutyrate, lactate, acetate, acetoacetate, and formate in CKD. Moreover, levels of alanine, glutamine, and glutamate were significantly higher. These changes were likely to be associated with complicated metabolic acidosis in CKD for counteracting systemic metabolic acidosis or increased protein catabolism from muscle. In contrast, levels of VLDL/LDL (CH2)n and N-acetylglycoproteins were decreased. Taken together, the observed changes of plasma metabolite profiles in CKD rats provide insights into the disturbed metabolism in early phase of CKD, in particular for the altered metabolism of acid-base and/or amino acids.
Integrated Metabolomics Research Group, Seoul Center, Korea Basic Science Institute, Seoul, Korea ; Department of Chemistry, Sungkyunkwan University, Suwon, Korea.
Ju-Ae
JA
Kim
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, Korea.
Hyo-Jung
HJ
Choi
Integrated Metabolomics Research Group, Seoul Center, Korea Basic Science Institute, Seoul, Korea ; Graduate School of Analytical Science and Technology, Chungnam University, Daejeon, Korea.
Yong-Kook
YK
Kwon
Department of Chemistry, Sungkyunkwan University, Suwon, Korea.
Do Hyun
DH
Ryu
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, Korea.
Tae-Hwan
TH
Kwon
Integrated Metabolomics Research Group, Seoul Center, Korea Basic Science Institute, Seoul, Korea ; Graduate School of Analytical Science and Technology, Chungnam University, Daejeon, Korea.
Geum-Sook
GS
Hwang
D000818:Animals; D007668:Kidney / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D055442:Metabolome / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000378:metabolism*; D059467:Transcriptome / Q000235:genetics