Table 2.
Kidney tissue, urine, and serum metabolites differing significantly by AKI, CPB/DHCA, or both (FDR < 0.05)
| Metabolite | Fold Change CPB/DHCA Without AKI vs. Controls | Fold Change CPB/DHCA With AKI vs. Controls | P Value | FDR | Significant Pairwise Comparisons |
|---|---|---|---|---|---|
| Kidney tissue | |||||
| Significant difference by AKI | |||||
| Tryptophan metabolism | |||||
| Anthranilate | 1.7 | 2.8 | 1.4 × 10−5 | 0.002 | 1-0; 2-0; 2-1 |
| Kynurenic acid | 1.6 | 2.8 | 4.0 × 10−4 | 0.01 | 2-0; 2-1 |
| Quinolinate | 1.6 | 2.4 | 4.7 × 10−4 | 0.01 | 1-0; 2-0; 2-1 |
| Indoleacrylic acid | 1.3 | 1.9 | 4.3 × 10−4 | 0.01 | 2-0; 2-1 |
| Purine metabolism | |||||
| Uric acid | 2.1 | 3.9 | 3.4 × 10−4 | 0.01 | 2-0; 2-1 |
| Allantoin | 1.4 | 3.7 | 4.6 × 10−4 | 0.01 | 2-0; 2-1 |
| Xanthosine | 2.0 | 3.9 | 8.4 × 10−4 | 0.02 | 1-0; 2-0; 2-1 |
| Other | |||||
| 2-Dehydrogluconate | 1.4 | 5.6 | 2.2 × 10−5 | 0.002 | 2-0; 2-1 |
| P-hydroxybenzoate | 1.6 | 2.7 | 1.2 × 10−4 | 0.008 | 1-0; 2-0; 2-1 |
| 2-OH-2-methylbutanedioic acid | 1.7 | 6.6 | 8 × 10−4 | 0.02 | 2-0; 2-1 |
| 4-Pyridoxic acid | 1.1 | 3.3 | 0.001 | 0.02 | 2-0; 2-1 |
| Imidazoleacetic acid | 0.87 | 2.8 | 0.002 | 0.03 | 2-0; 2-1 |
| Pyrophosphate | 1.4 | 2.2 | 0.003 | 0.03 | 2-0; 2-1 |
| Creatinine | 1.1 | 1.4 | 0.005 | 0.04 | 2-0; 2-1 |
| Significant difference by CPB/DHCA exposure only | |||||
| 3-Methylphenylacetic acid | 2.3 | 3.2 | 7 × 10−4 | 0.02 | 1-0; 2-0 |
| Malondialdehyde | 1.6 | 2.1 | 0.002 | 0.03 | 1-0; 2-0 |
| UDP-d-glucose | 1.8 | 2.4 | 0.003 | 0.03 | 1-0; 2-0 |
| Allantoate | 1.5 | 2.4 | 0.003 | 0.03 | 1-0; 2-0 |
| Methionine sulfoxide | 0.43 | 0.34 | 0.003 | 0.03 | 0-1; 0-2 |
| Thiamine | 3.6 | 3.8 | 0.004 | 0.04 | 1-0; 2-0 |
| Hydroxyphenylpyruvate | 1.4 | 2.1 | 0.004 | 0.04 | 2-0 |
| N-carbamoylaspartate | 1.6 | 2.5 | 0.005 | 0.04 | 2-0 |
| 8-OH-guanosine | 2.5 | 2.7 | 0.005 | 0.04 | 1-0; 2-0 |
| Urine | |||||
| Significant difference by AKI | |||||
| Ribose-5-phosphate | 5.5 | 9.7 | 6.7 × 10−7 | 3.1 × 10−5 | 1-0; 2-0; 2-1 |
| AMP | 4.1 | 8.8 | 8.5 × 10−7 | 3.1 × 10−5 | 1-0; 2-0; 2-1 |
| Putrescine | 4.3 | 10.6 | 2.2 × 10−6 | 6.9 × 10−5 | 1-0; 2-0; 2-1 |
| α-Ketoglutarate | 1.1 | 1.8 | 2.0 × 10−4 | 0.003 | 2-0; 2-1 |
| Phosphoenolpyruvate | 1.6 | 3.2 | 2.0 × 10−4 | 0.003 | 1-0; 2-0; 2-1 |
| Phosphorylcholine | 1.4 | 2.7 | 3.7 × 10−4 | 0.005 | 1-0; 2-0; 2-1 |
| Glycerophosphocholine | 1.4 | 2.1 | 5.6 × 10−4 | 0.006 | 2-0; 2-1 |
| Cytidine | 0.76 | 0.25 | 0.003 | 0.02 | 0-2; 1-2 |
| Glucose-6-phosphate | 1.5 | 3.5 | 0.004 | 0.03 | 2-0; 2-1 |
| Significant difference by CPB/DHCA exposure only | |||||
| Lactate | 7.6 | 6.5 | 6.7 × 10−9 | 1.2 × 10−6 | 1-0; 2-0 |
| Pyruvate | 8.2 | 6.9 | 1.5 × 10−8 | 1.4 × 10−6 | 1-0; 2-0 |
| Spermine | 8.8 | 12.1 | 6.1 × 10−8 | 3.7 × 10−6 | 1-0; 2-0 |
| Valine | 3.3 | 4.0 | 5.9 × 10−6 | 1.6 × 10−4 | 1-0; 2-0 |
| Hypoxanthine | 2.3 | 1.9 | 1.7 × 10−5 | 4 × 10−4 | 1-0; 2-0 |
| Phenylalanine | 2.6 | 3 | 6.6 × 10−5 | 0.001 | 1-0; 2-0 |
| Arginine | 3.3 | 2.8 | 1.9 × 10−4 | 0.003 | 1-0; 2-0 |
| Proline | 2 | 1.7 | 2.3 × 10−5 | 0.003 | 1-0; 2-0 |
| Glutamine | 1.7 | 2.3 | 5.2 × 10−4 | 0.006 | 1-0; 2-0 |
| Citrate | 1.8 | 1.9 | 8.3 × 10−4 | 0.009 | 1-0; 2-0 |
| Citrulline | 2.7 | 2.1 | 9.5 × 10−4 | 0.01 | 1-0; 2-0 |
| Isocitrate | 1.4 | 1.4 | 0.001 | 0.01 | 1-0; 2-0 |
| Lysine | 2.5 | 2 | 0.002 | 0.01 | 1-0; 2-0 |
| Nicotinate | 2.9 | 2.6 | 0.002 | 0.02 | 1-0; 2-0 |
| Pipecolic acid | 1.9 | 2.3 | 0.003 | 0.02 | 1-0; 2-0 |
| Taurine | 2.4 | 2.5 | 0.003 | 0.02 | 1-0; 2-0 |
| Tyrosine | 2.2 | 2 | 0.004 | 0.03 | 1-0; 2-0 |
| Indole-3-carboxylic acid | 1.5 | 1.8 | 0.004 | 0.03 | 1-0; 2-0 |
| Methionine | 1.4 | 1.7 | 0.004 | 0.03 | 1-0; 2-0 |
| Inosine | 1.3 | 1.2 | 0.008 | 0.047 | 1-0; 2-0 |
| Serine | 1.3 | 1.5 | 0.008 | 0.047 | 1-0; 2-0 |
| Serum | |||||
| Significant difference by AKI | |||||
| Pyroglutamic acid | 0.85 | 0.73 | 6.3 × 10−4 | 0.0009 | 0-1; 0-2; 1-2 |
| Significant difference by CPB/DHCA exposure only | |||||
| Inosine | 0.09 | 0.11 | 8.3 × 10−8 | 1.5 × 10−5 | 0-1; 0-2 |
| Uridine | 0.21 | 0.16 | 8 × 10−7 | 7.4 × 10−5 | 0-1; 0-2 |
| Adenosine | 0.06 | 0.13 | 6.1 × 10−5 | 0.003 | 0-1; 0-2 |
| Methionine | 0.55 | 0.53 | 7.3 × 10−5 | 0.003 | 0-1; 0-2 |
| Lactate | 1.8 | 1.9 | 1.1 × 10−4 | 0.004 | 1-0; 2-0 |
| Deoxyguanosine | 0.32 | 0.45 | 1.8 × 10−4 | 0.006 | 0-1; 0-2 |
| Sedoheptulose-1,7-phosphate | 1.9 | 2.3 | 3.1 × 10−4 | 0.008 | 1-0; 2-0 |
| Cytidine | 0.51 | 0.42 | 3.6 × 10−4 | 0.008 | 0-1; 0-2 |
| Anthranilate | 2.2 | 4.0 | 3.9 × 10−4 | 0.008 | 1-0; 2-0 |
| Malondialdehyde | 1.5 | 1.6 | 5.5 × 10−4 | 0.009 | 1-0; 2-0 |
| Arginine | 0.66 | 0.6 | 6.3 × 10−4 | 0.009 | 0-1; 0-2 |
| Pyruvate | 2.4 | 2.4 | 6.4 × 10−4 | 0.009 | 1-0; 2-0 |
| Glycoxylate | 1.7 | 2.0 | 6.9 × 10−4 | 0.009 | 1-0; 2-0 |
| Serine | 0.75 | 0.7 | 0.001 | 0.01 | 0-1; 0-2 |
| AMP | 0.01 | 0.01 | 0.001 | 0.01 | 0-1; 0-2 |
| CTP | 0.65 | 0.56 | 0.002 | 0.03 | 0-1; 0-2 |
| Lipoate | 2.8 | 2.2 | 0.003 | 0.03 | 1-0; 2-0 |
| Malate | 1.8 | 2.1 | 0.003 | 0.03 | 1-0; 2-0 |
For pairwise comparisons, 0 = mechanically ventilated control group, 1 = cardiopulmonary bypass with deep hypothermic circulatory arrest (CPB/DHCA) animals without acute kidney injury (AKI), and 2 = CPB/DHCA animals with AKI. The first number in each pairwise comparison represents the group with the higher level of the corresponding metabolite (e.g., anthranilate 1-0 = higher level of anthranilate in CPB/DHCA animals without AKI compared with mechanically ventilated controls). FDR, false discovery rate.