Table 3.
Metabolite-level differences between CKD and control participants in Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease
| Metabolite | Estimate | 95% CI | P Value |
|---|---|---|---|
| 4-Hydroxyphenylacetylglutamine | 2.75 | (2.22 to 3.27) | <0.001 |
| Orotidine | 2.36 | (1.81 to 2.9) | <0.001 |
| γ-CEHC glucuronide | 2.32 | (1.84 to 2.8) | <0.001 |
| Indoleacetylglutamine | 1.85 | (1.36 to 2.35) | <0.001 |
| Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC) | 1.83 | (1.38 to 2.28) | <0.001 |
| N6-succinyladenosine | 1.79 | (1.44 to 2.13) | <0.001 |
| Vanillactate | 1.65 | (1.27 to 2.03) | <0.001 |
| Adipoylcarnitine (C6-DC) | 1.53 | (1.12 to 1.95) | <0.001 |
| Suberoylcarnitine (C8-DC) | 1.52 | (0.99 to 2.04) | <0.001 |
| 1-Ribosyl-imidazoleacetate | 1.41 | (1.12 to 1.69) | <0.001 |
| C-glycosyltryptophan | 1.24 | (0.98 to 1.49) | <0.001 |
| Arabitol/xylitol | 1.22 | (0.99 to 1.45) | <0.001 |
| Hydroxyasparagine | 1.21 | (0.99 to 1.42) | <0.001 |
| 4-Hydroxyphenylacetate | 1.13 | (0.54 to 1.72) | <0.001 |
| N6-carbamoylthreonyladenosine | 1.11 | (0.88 to 1.34) | <0.001 |
| 5,6-Dihydrouridine | 1.06 | (0.84 to 1.29) | <0.001 |
| N-acetylneuraminate | 1.06 | (0.84 to 1.29) | <0.001 |
| Acisoga | 1.01 | (0.73 to 1.28) | <0.001 |
| N-acetylglutamine | 0.95 | (0.72 to 1.19) | <0.001 |
| Phenylacetylglutamine | 0.95 | (0.59 to 1.31) | <0.001 |
| Glutarylcarnitine (C5-DC) | 0.94 | (0.7 to 1.19) | <0.001 |
| N-acetyl-isoputreanine | 0.93 | (0.67 to 1.18) | <0.001 |
| 3-Hydroxy-3-methylglutarate | 0.92 | (0.68 to 1.16) | <0.001 |
| 3-Carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) | 0.89 | (0.25 to 1.53) | <0.001 |
| Pro-hydroxy-pro | 0.77 | (0.37 to 1.18) | <0.001 |
| N-acetyltaurine | 0.77 | (0.57 to 0.97) | <0.001 |
| N-acetylalanine | 0.75 | (0.61 to 0.88) | <0.001 |
| N-acetylvaline | 0.74 | (0.58 to 0.9) | <0.001 |
| Trimethylamine N-oxide | 0.73 | (0.29 to 1.18) | <0.001 |
| Aconitate [cis or trans] | 0.72 | (0.5 to 0.93) | <0.001 |
| Retinol (vitamin A) | 0.71 | (0.55 to 0.86) | <0.001 |
| 3-Carboxy-4-methyl-5-pentyl-2-furanpropionate (3-Cmpfp) | 0.70 | (0.45 to 0.96) | <0.001 |
| 1-Stearoyl-2-oleoyl-GPE (18:0/18:1) | 0.70 | (0.41 to 0.99) | <0.001 |
| Kynurenine | 0.60 | (0.45 to 0.75) | <0.001 |
| N6-acetyllysine | 0.56 | (0.4 to 0.71) | <0.001 |
| N-acetylputrescine | 0.54 | (0.35 to 0.73) | <0.001 |
| Behenoyl dihydrosphingomyelin (d18:0/22:0) | 0.45 | (0.18 to 0.73) | <0.001 |
| Glycosyl-N-(2-hydroxynervonoyl)-sphingosine (d18:1/24:1(2OH)) | 0.44 | (0.02 to 0.86) | 0.044 |
| γ-Glutamylleucine | 0.38 | (0.25 to 0.51) | <0.001 |
| Indoleacetate | 0.38 | (0.15 to 0.61) | 0.002 |
| Tricosanoyl sphingomyelin (d18:1/23:0) | 0.35 | (0.19 to 0.52) | <0.001 |
| Campesterol | 0.35 | (0.04 to 0.66) | 0.03 |
| Cholesterol | 0.35 | (0.23 to 0.47) | <0.001 |
| Sphingomyelin (d17:1/14:0, d16:1/15:0) | 0.34 | (0.14 to 0.55) | 0.001 |
| Lactosyl-N-nervonoyl-sphingosine (d18:1/24:1) | 0.32 | (0.16 to 0.48) | <0.001 |
| Lignoceroyl sphingomyelin (d18:1/24:0) | 0.30 | (0.16 to 0.44) | <0.001 |
| Sphingomyelin (d18:0/20:0, d16:0/22:0) | 0.30 | (0.04 to 0.56) | 0.03 |
| trans-4-Hydroxyproline | 0.29 | (0.1 to 0.49) | 0.003 |
| γ-Glutamylcitrulline | 0.27 | (0.06 to 0.48) | 0.02 |
| Sphingomyelin (d18:1/21:0, d17:1/22:0, d16:1/23:0) | 0.27 | (0.11 to 0.43) | 0.001 |
| 1-Arachidonoyl-GPE (20:4n6) | 0.24 | (0.12 to 0.35) | <0.001 |
| Sphingomyelin (d18:1/25:0, d19:0/24:1, d20:1/23:0, d19:1/24:0) | 0.23 | (0.03 to 0.42) | 0.02 |
| Glycosyl ceramide (d18:1/20:0, d16:1/22:0) | 0.22 | (0.06 to 0.38) | 0.008 |
| Behenoyl sphingomyelin (d18:1/22:0) | 0.20 | (0.09 to 0.3) | <0.001 |
| Myristoyl dihydrosphingomyelin (d18:0/14:0) | 0.18 | (0.03 to 0.33) | 0.02 |
| Tryptophan | −0.32 | (−0.43 to −0.21) | <0.001 |
| Arachidonoylcholine | 0.21 | (−0.01 to 0.43) | 0.07 |
| l-Urobilin | −0.27 | (−0.71 to 0.17) | 0.24 |
| Linoleoylcholine | 0.12 | (−0.08 to 0.32) | 0.24 |
| Palmitoylcholine | 0.11 | (−0.09 to 0.31) | 0.30 |
| Oleoylcholine | 0.12 | (−0.11 to 0.34) | 0.32 |
| 1-Linoleoyl-GPE (18:2) | 0.10 | (−0.1 to 0.3) | 0.32 |
| Hydroxy-CMPF | −0.24 | (−0.86 to 0.37) | 0.44 |
| 5-Methyluridine (ribothymidine) | 0.05 | (−0.12 to 0.22) | 0.57 |
| Epiandrosterone sulfate | −0.10 | (−0.67 to 0.47) | 0.74 |
| Pregnenediol disulfate (C21H34O8S2) | −0.06 | (−0.46 to 0.33) | 0.75 |
| 5α-Androstan-3α,17β-diol monosulfate (1) | 0.10 | (−0.53 to 0.73) | 0.76 |
| Isoursodeoxycholate | 0.06 | (−0.53 to 0.66) | 0.83 |
| Androsterone sulfate | −0.05 | (−0.56 to 0.46) | 0.84 |
| 5α-Pregnan-diol disulfate | −0.06 | (−0.69 to 0.58) | 0.86 |
| 5α-Androstan-3α,17β-diol monosulfate (2) | 0.05 | (−0.56 to 0.65) | 0.87 |
There were 71 metabolites significantly associated with neurocognitive z-scores reported in Table 2. Regression analyses identified that 56 of these had significant differences on the basis of CKD status in NiCK. Estimates are reported as for the difference between having CKD versus being a control participant and the number of two-fold unit differences in the metabolite level. Only tryptophan was measured at lower levels in children with CKD. CI, confidence interval; NiCK, Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease.