Table 2.
Concentrations of metabolites in healthy controls and participants with CKD
| Variable | Control (n=147) | CKD Stage 1 (n=340) | CKD Stage 2 (n=230) | CKD Stage 3 (n=219) | Jonckheere–Terpstra Statistic | P Value (1) | P Value (2) | P Value (3) | P Value (4) |
|---|---|---|---|---|---|---|---|---|---|
| Acetate | 4.667 (3.165–7.301) | 5.243 (3.444–8.798) | 5.675 (3.788–9.500) | 5.609 (3.236–8.990) | 1.950 | 0.051 | 0.103 | 0.026 | 0.484 |
| Acetone | 2.194 (1.553–4.023) | 1.812 (1.124–3.125) | 1.815 (1.153–3.158) | 2.748 (1.686–4.886) | 2.915 | 0.004 | 0.725 | 0.629 | 0.039 |
| Alanine | 26.338 (17.095–36.036) | 39.402 (30.095–59.174) | 37.561 (26.179–53.068) | 34.753 (22.971–57.849) | 3.507 | <0.001 | <0.001 | 0.313 | 0.639 |
| Betaine | 11.031 (7.303–16.060) | 15.698 (9.905–28.800) | 19.789 (11.599–37.861) | 29.999 (16.074–59.074) | 10.722 | <0.001 | <0.001 | 0.071 | <0.001 |
| Choline | 2.353 (1.653–3.743) | 4.453 (2.840–7.129) | 6.057 (3.375–11.359) | 10.317 (4.980–25.218) | 15.246 | <0.001 | <0.001 | 0.008 | <0.001 |
| Citrate | 345.159 (178.178–595.663) | 317.298 (177.718–528.377) | 250.976 (132.666–406.263) | 168.583 (89.775–273.460) | −9.088 | <0.001 | 0.091 | 0.003 | <0.001 |
| Creatine | 11.878 (6.221–31.115) | 16.479 (10.040–75.642) | 12.778 (8.120–30.244) | 13.745 (9.568–27.024) | −0.262 | 0.794 | 0.002 | 0.026 | 0.650 |
| Dimethylamine | 38.732 (31.733–51.443) | 46.887 (38.938–59.140) | 50.290 (39.519–67.108) | 56.361 (45.398–74.596) | 8.843 | <0.001 | 0.001 | 0.213 | 0.033 |
| Dimethylglycine | 4.608 (2.907–6.784) | 6.303 (4.157–9.596) | 6.091 (3.812–9.226) | 6.716 (3.797–10.010) | 3.685 | <0.001 | 0.507 | 0.402 | 0.214 |
| Formate | 17.859 (9.496–28.338) | 23.311 (15.471–34.072) | 17.638 (9.753–29.340) | 11.704 (6.328–21.213) | −6.234 | <0.001 | 0.001 | 0.273 | 0.257 |
| Fumarate | 0.270 (0.167–0.477) | 0.338 (0.000–0.670) | 0.435 (0.110–0.977) | 0.768 (0.170–1.633) | 7.123 | <0.001 | 0.022 | 0.007 | 0.005 |
| Glucose | 51.648 (39.709–72.577) | 52.651 (40.486–74.541) | 61.008 (39.631–130.392) | 70.372 (39.425–197.467) | 3.966 | <0.001 | 0.008 | 0.965 | 0.505 |
| Glycerol | 690.886 (465.887–1009.953) | 50.393 (31.780–90.542) | 56.488 (31.014–95.777) | 70.067 (40.801–121.037) | −9.300 | <0.001 | <0.001 | 0.879 | 0.033 |
| Glycine | 77.047 (49.174–115.894) | 114.684 (76.066–167.389) | 86.248 (54.209–137.342) | 72.595 (41.638–137.428) | −3.318 | 0.001 | <0.001 | 0.957 | 0.256 |
| Hydroxyisobutyrate | 7.211 (5.590–9.441) | 7.537 (5.874–9.427) | 6.979 (5.177–8.665) | 6.387 (4.801–8.038) | −5.037 | <0.001 | 0.942 | 0.018 | 0.011 |
| Indoxylsulfate | 18.807 (11.286–27.956) | 17.304 (8.041–30.286) | 17.331 (9.134–29.430) | 22.023 (13.323–36.911) | 2.033 | 0.042 | 0.870 | 0.632 | 0.971 |
| Isoleucine | 1.421 (1.109–1.726) | 2.088 (1.615–2.773) | 1.837 (1.327–2.666) | 1.838 (1.288–2.915) | 3.538 | <0.001 | 0.873 | 0.999 | 0.089 |
| Lactate | 9.949 (6.886–13.560) | 15.017 (9.836–23.819) | 13.885 (8.696–23.399) | 17.684 (10.234–29.786) | 6.523 | <0.001 | <0.001 | 0.227 | 0.995 |
| Leucine | 3.136 (2.470–4.050) | 4.986 (3.816–6.309) | 4.668 (3.249–6.827) | 4.777 (3.072–7.156) | 5.801 | <0.001 | <0.001 | 0.690 | 0.019 |
| Methylhistidine | 20.664 (17.383–26.109) | 5.822 (4.670–7.412) | 5.260 (3.914–7.539) | 4.892 (3.363–7.467) | 2.600 | <0.001 | <0.001 | 0.824 | 0.095 |
| Methylnicotinamide | 6.228 (3.872–10.715) | 4.418 (2.691–7.469) | 4.333 (2.566–6.660) | 3.941 (2.256–6.011) | −5.273 | <0.001 | <0.001 | 0.938 | 0.510 |
| Phenylalanine | 30.785 (13.261–62.279) | 34.693 (17.582–65.706) | 37.297 (19.185–71.489) | 51.026 (26.508–91.948) | 5.423 | <0.001 | 0.588 | 0.125 | 0.007 |
| Pyruvate | 2.034 (1.247–2.861) | 3.748 (2.550–5.222) | 3.316 (2.051–5.159) | 3.384 (2.295–5.405) | 5.476 | <0.001 | <0.001 | 0.462 | 0.262 |
| Taurine | 162.589 (113.690–238.590) | 172.042 (114.344–252.347) | 174.114 (105.643–253.353) | 160.440 (94.312–231.019) | −1.118 | 0.264 | 0.218 | 0.315 | 0.629 |
| Threonine | 13.075 (9.404–19.088) | 19.742 (14.967–27.493) | 16.691 (11.752–24.083) | 14.986 (8.702–27.808) | −0.016 | 0.987 | <0.001 | 0.696 | 0.371 |
| TMAO | 52.447 (26.521–115.009) | 85.924 (42.980–195.251) | 107.220 (54.524–249.696) | 128.553 (68.933–291.752) | 7.852 | <0.001 | 0.004 | 0.084 | 0.191 |
| Tryptophan | 7.116 (5.106–9.113) | 8.242 (5.975–11.075) | 7.409 (5.395–10.204) | 6.860 (4.396–9.357) | −1.869 | 0.062 | <0.001 | 0.212 | 0.351 |
| Valine | 3.957 (3.223–4.912) | 5.822 (4.670–7.412) | 5.260 (3.914–7.539) | 4.892 (3.363–7.467) | 2.600 | 0.009 | <0.001 | 0.824 | 0.095 |
P-value (1): Jonckheere–Terpstra test; P-value (2): control versus CKD stage 1; P-value (3): CKD stage 1 versus stage 2; P-value (4): CKD stage 2 versus stage 3. All the concentration of each metabolite was adjusted by urine creatinine. TMAO, trimethylamine-N-oxide.