Table 1.
Changes of renal functions.
Figure 1.
Representative 600 MHz 1H nuclear magnetic resonance (NMR) spectra of plasma obtained from 5/6 nephrectomized CKD rats and sham-operated control rats at 4 weeks (A) or 8 weeks (B) after 5/6 nephrectomy and sham operation.
1, VLDL/LDL CH3; 2, Leucine/Isoleucine; 3, Valine; 4, β-hydroxybutyrate; 5, VLDL/LDL (CH2)n; 6, Alanine; 7, Lipid CH2CH2C = O; 8, Lipid CH2CH2C = C; 9, Arginine; 10, Acetate; 11, N-acetylglycoproteins; 12, Glutamine; 13, Methionine; 14, Lipid CH2C = O; 15, Acetoacetate; 16, Pyruvate; 17, Glutamate/Glutamine; 18, Citrate; 19, Dimethylamine (DMA); 20, Trimethylamine (TMA); 21, Creatinine; 22, Choline; 23, Trimethylamine-N-oxide (TMAO); 24, O-phosphocholine; 25, Myo-inositol; 26, Glycine; 27, Glucose/Maltose; 28, Lactate; 29, Urea; and 30, Formate. CKD, chronic kidney disease.
Figure 2.
Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) score scatter plots and permutation tests of PLS-DA obtained from the 1H NMR spectra of plasma at 4 weeks (A, C, E) or 8 weeks (B, D, F) after 5/6 nephrectomy and sham operation, demonstrating a clear differentiation between the two groups.
CKD, chronic kidney disease.
Figure 3.
Orthogonal partial least-squares discriminant analysis (OPLS-DA) score and coefficient loading plots derived from the 1H NMR spectra derived from plasma at 4 weeks (A, C) or 8 weeks (B, D) after 5/6 nephrectomy and sham operation.
The OPLS-DA coefficient loading plot shows a significant difference in the metabolite levels between the two groups. 1, VLDL/LDL CH3; 2, β-hydroxybutyrate; 3, VLDL/LDL (CH2)n; 4, Alanine; 5, Lipid CH2CH2C = O; 6, Lipid CH2CH2C = C; 7, Arginine; 8, Acetate; 9, N-acetylglycoproteins; 10, Methionine; 11, Lipid CH2C = O; 12, Acetoacetate; 13, Glutamine/Glutamate; 14, Citrate; 15, Trimethylamine (TMA); 16, Choline; 17, Trimethylamine-N-oxide (TMAO); 18, O-phosphocholine; 19, Glucose/Maltose; 20, Lactate; 21, Urea; and 22, Formate. CKD, chronic kidney disease.
Figure 4.
PCA score scatter and loading plots of metabolites quantification through targeted profiling of plasma at 4 weeks (A, B) and 8 (C, D), respectively.
The loading plots were produced from the score plots which showed a significant differentiation between the two groups. CKD, chronic kidney disease.
Figure 5.
Quantification of changes of plasma metabolites in rats with CKD at 4 weeks and 8 weeks after 5/6 nephrectomy, respectively.
*, **, *** indicate bonferroni corrected P<0.05, <0.01, and <0.001, respectively.
Figure 6.
A diagram for the changes in plasma metabolites in CKD.
The metabolite profiles of plasma in rats with CKD showed significantly increased levels of lactate, pyruvate, acetoacetate, β-hydroxybutyrate, glutamine, glutamate, and citrate. Metabolic acidosis is commonly complicated in CKD, due to both decreased net acid excretion and impaired regeneration of bicarbonate. This could change the citrate reabsorption in renal tubular cells, which metabolism generates HCO3– ions producing an alkalinizing effect. Moreover, increased protein breakdown and insensitivity to epinephrine in muscle in CKD could induce the increases of alanine, glutamate, and glutamine in plasma.
Table 2.
1H chemical shift and relative concentrations of metabolites observed in plasma from CKD and sham-operated groups.