Table 2.
Urinary metabolites significantly differing between groups with and without AKI
| Metabolites | Metabolic pathways involved | Boston |
Birmingham |
Overall |
|||
|---|---|---|---|---|---|---|---|
| FC | Raw P | FC | Raw P | FC | Raw P | ||
| Decreased | |||||||
| Xanthine (+) | Purine, caffeine | 0.26 | 4.00e−6 | 0.30 | 1.52e−6 | 0.28 | 8.14e−10 |
| N,N-dimethylarginine (+) | Arginine, urea | 0.36 | 5.45e−6 | 0.48 | 0.00054 | 0.40 | 1.61e−8 |
| Cyclic AMP (−) | Purine, cellular signaling | 0.42 | 5.80e−6 | 0.43 | 0.00017 | 0.41 | 4.87e−7 |
| N-acetylaspartate (−) | Aspartate/glutamate, cellular signaling, acetyl-CoA | 0.32 | 2.92e−5 | 0.42 | 0.00022 | 0.35 | 2.94e−8 |
| Hypoxanthine (+) | Purine | 0.25 | 4.91e−5 | 0.27 | 0.0016 | 0.27 | 1.32e−7 |
| Pantothenate (+) | Beta-alanine, pantothenate, and CoA | 0.27 | 5.98e−5 | 0.29 | 0.0016 | 0.26 | 3.17e−7 |
| Xanthosine (+) | Purine | 0.43 | 7.11e−5 | 0.80 | 0.20 | 0.59 | 0.0023 |
| N-α-acetyl-lysine (+) | Lysine | 0.53 | 0.0026 | 0.36 | 0.0057 | 0.44 | 4.22e−5 |
| Adenosine (+) | Purine, cell signaling | 0.25 | 0.010 | 0.38 | 0.026 | 0.30 | 0.00043 |
| Transaconitate (−) | TCA cycle | 0.21 | 0.015 | 0.23 | 0.00046 | 0.21 | 7.95e−5 |
| Urate (+) | Purine | 0.75 | 0.023 | 0.77 | 0.20 | 0.77 | 0.080 |
| Glycocholate (+) | Bile acid, lipid metabolism | 0.38 | 0.027 | 0.71 | 0.085 | 0.47 | 0.0040 |
| Histidine (+) | Histidine, β-alanine, ammonia recycling | 0.25 | 0.033 | 0.15 | 9.38e−6 | 0.24 | 0.00012 |
| Methylglutarate (−) | Lipid, fatty acid metabolism | 0.46 | 0.039 | 0.15 | 0.24 | 0.19 | 0.023 |
| 1-Methyl-L-histidine (+) | Histidine | 0.68 | 0.042 | 0.47 | 0.00036 | 0.60 | 0.00031 |
| Tryptophan (+) | Tryptophan | 0.37 | 0.077 | 0.31 | 8.45e−5 | 0.33 | 0.0020 |
| Isocitrate (−) | TCA cycle | 0.92 | 0.34 | 0.42 | 0.00016 | 0.38 | 0.23 |
| Tyrosine (+) | Tyrosine, phenylalanine, catecholamine | 0.67 | 0.47 | 0.31 | 0.00020 | 0.50 | 0.014 |
| Tryptophan (−) | (see above) | 0.55 | 0.42 | 0.30 | 0.0044 | 0.27 | 0.14 |
| Hypoxanthine (−) | (see above) | 0.37 | 0.20 | 0.41 | 0.0047 | 0.36 | 0.13 |
| Tyrosine (−) | (see above) | 0.67 | 0.47 | 0.33 | 0.0080 | 0.30 | 0.64 |
| Betaine (+) | Betaine, glycine/serine, methionine | 0.51 | 0.19 | 0.23 | 0.030 | 0.35 | 0.012 |
| N-acetylglutamate (−) | Glycine/serine, glutamate | 1.01 | 0.62 | 0.28 | 0.00069 | 0.25 | 0.23 |
| Glutarate (−) | Tryptophan, lysine | 0.15 | 0.00011 | — | — | — | — |
| S-adenosylmethionine (+) | Tryptophan, purine, nicotinamide, methionine, glycine/serine, arginine, proline, betaine, carnitine, histidine, tyrosine, spermine/spermidine, catecholamine | 0.49 | 0.0026 | — | — | — | — |
| N-acetylgalactosamine (−) | Carbohydrates | 0.38 | 0.0058 | — | — | — | — |
| Riboflavin (−) | Riboflavin | 0.65 | 0.022 | — | — | — | — |
| Kynurenine (+) | Tryptophan | 0.66 | 0.041 | — | — | — | — |
| Histidine (−) | (see above) | — | — | 0.10 | 1.94e−6 | — | — |
| Ethylmalonate (−) | Lipids | — | — | 0.17 | 4.04e−5 | — | — |
| N-acetylasparagine (+) | Asparagine | — | — | 0.25 | 0.00015 | — | — |
| Nicotinamide (+) | Nicotinamide | — | — | 0.32 | 0.00031 | — | — |
| Dihydrobiopterin (+) | Pterine, catecholamine | — | — | 0.32 | 0.00050 | — | — |
| Trigonelline (+) | Nicotinamide | — | — | 0.27 | 0.0080 | — | — |
| 2-Hydroxybutyrate (−) | Threonine, methionine, cysteine | — | — | 0.49 | 0.011 | — | — |
| Lysine (+) | Lysine | — | — | 0.048 | 0.016 | — | — |
| 4-Hydroxybenzoate (+) | Exogenous | — | — | 0.48 | 0.024 | — | — |
| Theobromine (+) | Caffeine | — | — | 0.082 | 0.025 | — | — |
| 3-Hydroxyanthranilate (+) | Tryptophan | — | — | 0.22 | 0.026 | — | — |
| Increased | |||||||
| Kynurenate (+) | Tryptophan | 3.26 | 0.00021 | 1.43 | 0.36 | 2.21 | 0.00056 |
| Kynurenate (−) | (see above) | 2.78 | 0.0018 | 1.97 | 0.071 | 2.53 | 0.00056 |
| Glucuronate (−) | Inositol, carbohydrate | 1.29 | 0.24 | 4.05 | 0.0020 | 1.66 | 0.014 |
| Leucine (+) | Valine/leucine/isoleucine | 3.28 | 0.012 | — | — | — | — |
| Lactose (+) | Exogenous | 2.35 | 0.049 | — | — | — | — |
| Guanidinosuccinate (+) | Uremia | — | — | 8.72 | 5.53e−7 | — | — |
| Mixed | |||||||
| Glutarylcarnitine (+) | Lipids, fatty acids | 1.93 | 0.0024 | 0.51 | 0.0081 | 0.57 | 0.94 |
| Riboflavin (+) | (see above) | 0.64 | 0.039 | 1.16 | 0.56 | 0.80 | 0.033 |
| Citramalate (−) | Lipids, fatty acids | 0.29 | 0.014 | 1.02 | 0.58 | 0.77 | 0.14 |
| Methionine (+) | Betaine, glycine/serine, methionine, spermine/spermidine | 2.12 | 0.13 | 0.41 | 0.0011 | 1.33 | 0.90 |
| Valine (+) | Propanoate, valine/leucine/isoleucine | 1.66 | 0.22 | 0.42 | 0.0015 | 0.95 | 0.53 |
| Phenylalanine (+) | Phenylalanine, tyrosine, catecholamine | 1.73 | 0.13 | 0.55 | 0.0081 | 1.15 | 0.90 |
AKI, acute kidney injury; AMP, adenosine monophosphate; AUC, area under the curve; CoA, coenzyme A; FC, fold change; TCA, tricarboxylic acid.
Metabolite data used for analysis are peak AUC by liquid chromatography-tandem mass spectrometry for each metabolite, with values for each participant divided by their respective peak AUC of creatinine. FC compares the log2-transformed ratio (AKI/no AKI) between each metabolite in each group. P values are derived from t test without multiple comparison corrections after transformation to achieve Gaussian distributions.