Table 4.
Urine Metabolite Changes in Alkali Compared to Control Periods†
| Metabolite | ||||
|---|---|---|---|---|
|
| ||||
| Fold-Change | p | FDR-adj p | sPLS-DA‡ | |
| CKD (n=8) | ||||
| 3-Indoleacetic Acid | 1.53 | <0.001 | 0.009 | 1 (0.98) |
| Citric Acid/Isocitric Acid | 1.50 | <0.001 | 0.009 | 1 (1) |
| Glutaric Acid | 1.30 | <0.001 | 0.009 | 1 (1) |
|
| ||||
| Azelaic Acid | 1.34 | 0.007 | 0.2 | |
| Succinic Acid | 1.33 | 0.008 | 0.2 | 1 (0.42) |
| Fumaric Acid | 1.29 | 0.009 | 0.2 | 1 (0.38) |
| Ethylmalonic Acid | 1.12 | 0.01 | 0.2 | -- |
| /γ-Hydroxybutyric Acid | ||||
| Adipic Acid | 1.43 | 0.01 | 0.2 | 1 (0.38) |
| Alpha-Ketoglutarate | 1.24 | 0.02 | 0.3 | -- |
| Methylmalonic Acid | 1.25 | 0.03 | 0.3 | -- |
| Guaiacol | 1.62 | 0.03 | 0.3 | -- |
| Decanoic Acid* | 1.55 | 0.03 | 0.3 | -- |
| Tricarballylic Acid€ | 1.66 | 0.03 | 0.4 | -- |
| p-Cresol | 1.21 | 0.04 | 0.4 | -- |
| Glycolic Acid* | 1.14 | 0.04 | 0.4 | -- |
| Non-CKD (n=6) | ||||
| Palmitic Acid | 0.58 | 0.002 | 0.1 | 1 (1) |
| o-Hydroxyhippuric Acid | 0.48 | 0.006 | 0.2 | 1 (1) |
| Stearic Acid | 0.59 | 0.007 | 0.2 | 1 (0.98) |
| 3-Hydroxybenzoic Acid | 0.62 | 0.01 | 0.3 | 1 (0.98) |
| N-Methylglutamic Acid | 0.69 | 0.01 | 0.3 | 1 (0.96) |
| Pyruvic Acid | 0.72 | 0.02 | 0.3 | 1 (1) |
| 1,2-Propanediol | 0.71 | 0.02 | 0.3 | 1 (0.82) |
| Mandelic Acid | 0.77 | 0.02 | 0.3 | 1 (0.84) |
| N-2-Furoylglycine | 0.58 | 0.04 | 0.4 | 1 (0.78) |
| Uracil | 0.79 | 0.04 | 0.4 | 1 (0.36) |
| 2,3-Dihydroxybenzoic Acid | 0.70 | 0.05 | 0.4 | 1 (0.66) |
| Catechol | 0.74 | 0.05 | 0.4 | 1 (0.68) |
| Oxalic Acid | 0.79 | 0.05 | 0.4 | 1 (0.60) |
Note: Darkened rows represent metabolite changes strongly supported by both linear mixed models of individual metabolites and sparse least squares discriminant analysis (sPLS-DA) identifying multivariate representations with strong and stable loading. Loadings with stability <0.35 are not depicted. Metabolites present in sample blanks at levels >0.5 times the levels detected in samples were removed from the table. These included: myristic acid/pentadecanol; nonanoic acid; tiglic acid; glycerol; undecanoic acid/1-dodecanol. Metabolites are annotated in CAS as acids but excreted primarily as organic anions at physiologic urine pH given generally low pKa for most. Acid nomenclature has been retained here but they are discussed as their conjugate base form throughout the remainder of the article.
sPLS-DA indicates metabolites that also loaded on components using sPLS-DA by indicating the loaded component number (stability or proportion of cross-validated models in which the metabolite was selected).
Indicates metabolite detected frequently in sample blanks at concentration 0.25-0.49 of sample concentrations.
Metabolite was imputed in ~50% of samples due to missing data. Metabolites missing in more than 50% of samples were not imputed or further analyzed.