Table 2.
Regression coefficients for metabolites significantly associated with proteinuria in the AASK, the MDRD study, or both, and summary of missingness across samples
| Metabolite | AASK | MDRD | Meta-Analysis | Missingness in AASK (%) | Missingness in MDRD (%) | |||
|---|---|---|---|---|---|---|---|---|
| β Coefficient (95% CI) | P Value | β Coefficient (95% CI) | P Value | β Coefficient (95% CI) | P Value | |||
| 4-hydroxychlorothalonil | −0.33 (−0.37 to −0.29) | <1.0×10−31 | −0.36 (−0.40 to −0.32) | <1.0×10−31 | −0.35 (−0.37 to −0.32) | <1.0×10−31 | 172 (18) | 63 (10) |
| 1,5-anhydroglucitol (1,5-AG) | −0.09 (−0.12 to −0.07) | 1.6×10−14 | −0.15 (−0.19 to −0.12) | 1.4×10−15 | −0.11 (−0.13 to −0.09) | 4.2×10−28 | 0 (0) | 0 (0) |
| 1-stearoyl-2-arachidonoyl-GPE (18:0/20:4) | 0.07 (0.05 to 0.09) | 1.3×10−11 | 0.05 (0.02 to 0.07) | 6.8×10−4 | 0.06 (0.04 to 0.08) | 5.8×10−14 | 0 (0) | 0 (0) |
| 1-stearoyl-GPE (18:0) | 0.05 (0.03 to 0.07) | 5.0×10−9 | 0.04 (0.02 to 0.06) | 2.3×10−5 | 0.05 (0.03 to 0.06) | 4.1×10−13 | 0 (0) | 0 (0) |
| 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) | −0.10 (−0.15 to −0.05) | 8.2×10−5 | −0.19 (−0.25 to −0.13) | 2.1×10−9 | −0.14 (−0.17 to −0.10) | 4.0×10−12 | 0 (0) | 0 (0) |
| 1-stearoyl-2-arachidonoyl-GPI (18:0/20:4) | 0.04 (0.03 to 0.06) | 3.9×10−9 | 0.03 (0.01 to 0.05) | 0.001 | 0.04 (0.03 to 0.05) | 1.5×10−11 | 0 (0) | 1 (0) |
| Aspartate | 0.02 (0.01 to 0.03) | 9.3×10−4 | 0.04 (0.03 to 0.05) | 2.4×10−9 | 0.03 (0.02 to 0.04) | 4.4×10−11 | 0 (0) | 0 (0) |
| 1-palmitoyl-2-arachidonoyl-GPE (16:0/20:4) | 0.07 (0.05 to 0.09) | 1.2×10−9 | 0.04 (0.01 to 0.07) | 0.007 | 0.06 (0.04 to 0.08) | 9.7×10−11 | 0 (0) | 0 (0) |
| 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE (P-16:0/20:4) | 0.05 (0.03 to 0.07) | 1.2×10−5 | 0.05 (0.03 to 0.07) | 3.4×10−6 | 0.05 (0.03 to 0.06) | 1.3×10−10 | 0 (0) | 0 (0) |
| Retinol (vitamin A) | 0.07 (0.05 to 0.09) | 2.0×10−13 | 0.02 (−0.00 to 0.03) | 0.05 | 0.04 (0.03 to 0.05) | 1.6×10−10 | 0 (0) | 0 (0) |
| 1-palmitoyl-GPE (16:0) | 0.05 (0.04 to 0.07) | 1.2×10−8 | 0.03 (0.01 to 0.05) | 0.01 | 0.04 (0.03 to 0.06) | 3.8×10−10 | 0 (0) | 0 (0) |
| 4-acetamidobutanoate | 0.08 (0.05 to 0.10) | 5.6×10−12 | 0.02 (−0.00 to 0.04) | 0.08 | 0.04 (0.03 to 0.06) | 2.5×10−9 | 2 (0) | 1 (0) |
| 1-(1-enyl-palmitoyl)-2-oleoyl-GPE (P-16:0/18:1) | 0.04 (0.02 to 0.06) | 8.3×10−4 | 0.06 (0.03 to 0.08) | 5.8×10−6 | 0.05 (0.03 to 0.06) | 2.2×10−8 | 3 (0) | 6 (1) |
| N6-carbamoylthreonyladenosine | 0.04 (0.03 to 0.05) | 5.9×10−10 | 0.01 (−0.00 to 0.02) | 0.17 | 0.03 (0.02 to 0.04) | 2.9×10−8 | 0 (0) | 0 (0) |
| N-palmitoyl-sphingosine (d18:1/16:0) | 0.03 (0.01 to 0.04) | 7.9×10−4 | 0.04 (0.02 to 0.05) | 8.7×10−6 | 0.03 (0.02 to 0.04) | 3.1×10−8 | 0 (0) | 0 (0) |
| N2,N5-diacetylornithine | 0.10 (0.07 to 0.13) | 3.0×10−11 | 0.01 (−0.02 to 0.05) | 0.42 | 0.06 (0.04 to 0.09) | 3.7×10−8 | 9 (1) | 6 (1) |
| 3-hydroxy-5-cholestenoic acid | −0.04 (−0.06 to −0.01) | 0.001 | −0.05 (−0.08 to −0.03) | 1.3×10−5 | −0.05 (−0.06 to −0.03) | 8.5×10−8 | 1 (0) | 0 (0) |
| 1-palmitoyl-2-oleoyl-GPE (16:0/18:1) | 0.07 (0.05 to 0.10) | 1.5×10−7 | 0.03 (−0.00 to 0.07) | 0.06 | 0.06 (0.04 to 0.08) | 9.4×10−8 | 4 (0) | 3 (0) |
| O-sulfo-L-tyrosine | 0.05 (0.04 to 0.07) | 1.6×10−11 | 0.00 (−0.02 to 0.02) | 0.88 | 0.03 (0.02 to 0.04) | 1.2×10−7 | 0 (0) | 0 (0) |
| 1-palmitoyl-2-arachidonoyl-GPC (16:0/20:4) | 0.03 (0.02 to 0.04) | 7.2×10−8 | 0.01 (−0.03 to 0.04) | 0.69 | 0.03 (0.02 to 0.04) | 1.3×10−7 | 0 (0) | 3 (0) |
| 6-hydroxyindole sulfate | 0.08 (0.05 to 0.11) | 5.9×10−8 | 0.03 (−0.01 to 0.07) | 0.11 | 0.06 (0.04 to 0.08) | 1.4×10−7 | 1 (0) | 0 (0) |
| Cholesterol | 0.03 (0.01 to 0.04) | 5.7×10−4 | 0.03 (0.02 to 0.05) | 7.0×10−5 | 0.03 (0.02 to 0.04) | 1.4×10−7 | 0 (0) | 0 (0) |
| 1-stearoyl-2-oleoyl-GPE (18:0/18:1) | 0.07 (0.04 to 0.09) | 3.6×10−6 | 0.04 (0.01 to 0.08) | 0.01 | 0.06 (0.04 to 0.08) | 1.7×10−7 | 1 (0) | 0 (0) |
| 3-methylglutaconate | 0.06 (0.04 to 0.08) | 9.2×10−9 | 0.01 (−0.02 to 0.04) | 0.44 | 0.04 (0.03 to 0.06) | 1.8×10−7 | 0 (0) | 0 (0) |
| 1-palmitoyl-2-linoleoyl-GPE (16:0/18:2) | 0.06 (0.04 to 0.08) | 1.9×10−6 | 0.03 (0.01 to 0.06) | 0.02 | 0.05 (0.03 to 0.07) | 2.4×10−7 | 0 (0) | 0 (0) |
| 1-stearoyl-2-linoleoyl-GPE (18:0/18:2) | 0.06 (0.04 to 0.08) | 8.1×10−7 | 0.03 (0.00 to 0.06) | 0.04 | 0.05 (0.03 to 0.06) | 2.9×10−7 | 0 (0) | 1 (0) |
| N-palmitoyl-sphinganine (d18:0/16:0) | 0.04 (0.01 to 0.07) | 0.004 | 0.06 (0.03 to 0.08) | 6.2×10−5 | 0.05 (0.03 to 0.07) | 7.5×10−7 | 47 (5) | 1 (0) |
| 1-palmitoyl-2-oleoyl-GPC (16:0/18:1) | 0.03 (0.02 to 0.04) | 2.2×10−6 | 0.01 (−0.00 to 0.03) | 0.08 | 0.02 (0.01 to 0.03) | 9.8×10−7 | 0 (0) | 0 (0) |
| N2,N2-dimethylguanosine | 0.05 (0.03 to 0.06) | 4.0×10−10 | 0.00 (−0.01 to 0.02) | 0.88 | 0.03 (0.02 to 0.04) | 1.4×10−6 | 0 (0) | 2 (0) |
| 1-stearoyl-2-arachidonoyl-GPC (18:0/20:4) | 0.03 (0.01 to 0.04) | 1.2×10−5 | 0.02 (−0.00 to 0.04) | 0.06 | 0.02 (0.01 to 0.03) | 1.9×10−6 | 0 (0) | 0 (0) |
| 1-palmitoyl-2-linoleoyl-GPC (16:0/18:2) | 0.02 (0.01 to 0.03) | 1.2×10−6 | 0.01 (−0.00 to 0.02) | 0.22 | 0.02 (0.01 to 0.02) | 2.5×10−6 | 0 (0) | 0 (0) |
| Methylsuccinate | 0.04 (0.02 to 0.05) | 1.6×10−5 | 0.03 (−0.00 to 0.06) | 0.06 | 0.04 (0.02 to 0.05) | 2.6×10−6 | 2 (0) | 23 (4) |
| 1-arachidonoyl-GPE (20:4) | 0.04 (0.02 to 0.05) | 3.6×10−6 | 0.02 (−0.00 to 0.03) | 0.11 | 0.03 (0.02 to 0.04) | 4.5×10−6 | 0 (0) | 0 (0) |
| N6-succinyladenosine | 0.05 (0.03 to 0.07) | 3.6×10−8 | 0.00 (−0.02 to 0.03) | 0.86 | 0.03 (0.02 to 0.05) | 6.4×10−6 | 9 (1) | 3 (0) |
| Kynurenate | 0.05 (0.03 to 0.07) | 1.5×10−6 | 0.01 (−0.01 to 0.04) | 0.28 | 0.04 (0.02 to 0.05) | 6.6×10−6 | 1 (0) | 1 (0) |
| 3-hydroxy-3-methylglutarate | 0.04 (0.02 to 0.05) | 2.7×10−5 | 0.02 (−0.00 to 0.04) | 0.06 | 0.03 (0.02 to 0.04) | 7.5×10−6 | 0 (0) | 0 (0) |
| 1-palmitoyl-2-arachidonoyl-GPI (16:0/20:4) | 0.05 (0.03 to 0.07) | 8.1×10−6 | 0.02 (−0.01 to 0.05) | 0.25 | 0.04 (0.02 to 0.06) | 9.5×10−6 | 3 (0) | 44 (7) |
| N-acetyl-3-methylhistidine | 0.14 (0.07 to 0.20) | 1.7×10−5 | 0.06 (−0.00 to 0.12) | 0.05 | 0.10 (0.05 to 0.14) | 9.8×10−6 | 152 (16) | 49 (8) |
| 2-stearoyl-GPE (18:0) | 0.05 (0.03 to 0.07) | 8.7×10−6 | 0.02 (−0.01 to 0.05) | 0.16 | 0.04 (0.02 to 0.06) | 1.2×10−5 | 0 (0) | 9 (1) |
| Pseudouridine | 0.03 (0.02 to 0.04) | 2.3×10−6 | 0.01 (−0.01 to 0.02) | 0.46 | 0.02 (0.01 to 0.03) | 1.7×10−5 | 0 (0) | 0 (0) |
| 3-indoxyl sulfate | 0.07 (0.04 to 0.09) | 3.8×10−7 | 0.01 (−0.02 to 0.04) | 0.56 | 0.04 (0.02 to 0.06) | 2.1×10−5 | 0 (0) | 0 (0) |
| Glycosyl-N-palmitoyl-sphingosine | 0.01 (−0.01 to 0.02) | 0.33 | 0.04 (0.03 to 0.06) | 7.4×10−7 | 0.02 (0.01 to 0.04) | 2.5×10−5 | 0 (0) | 0 (0) |
| Pyridoxate | 0.09 (0.06 to 0.13) | 7.2×10−8 | −0.02 (−0.07 to 0.04) | 0.54 | 0.06 (0.03 to 0.09) | 3.2×10−5 | 0 (0) | 0 (0) |
| 3-acetylphenol sulfate | 0.05 (−0.01 to 0.10) | 0.08 | 0.11 (0.06 to 0.17) | 5.9×10−5 | 0.08 (0.04 to 0.12) | 4.7×10−5 | 356 (37) | 107 (17) |
| Arabitol/xylitol | 0.04 (0.02 to 0.05) | 1.6×10−5 | 0.01 (−0.01 to 0.03) | 0.32 | 0.03 (0.01 to 0.04) | 6.4×10−5 | 0 (0) | 0 (0) |
| 1-palmitoyl-2-linoleoyl-GPI (16:0/18:2) | 0.04 (0.02 to 0.06) | 3.8×10−5 | 0.01 (−0.02 to 0.04) | 0.54 | 0.03 (0.01 to 0.04) | 6.4×10−5 | 0 (0) | 13 (2) |
| Indolin-2-one | 0.06 (0.03 to 0.09) | 2.1×10−5 | 0.01 (−0.02 to 0.05) | 0.46 | 0.04 (0.02 to 0.07) | 1.5×10−4 | 186 (19) | 6 (1) |
| 1-palmitoleoyl-GPC (16:1) | 0.03 (0.02 to 0.05) | 2.2×10−5 | 0.01 (−0.01 to 0.03) | 0.39 | 0.02 (0.01 to 0.03) | 1.5×10−4 | 0 (0) | 0 (0) |
| 1-methylimidazoleacetate | 0.04 (0.02 to 0.06) | 1.8×10−6 | 0.00 (−0.02 to 0.02) | 0.80 | 0.02 (0.01 to 0.04) | 1.6×10−4 | 0 (0) | 0 (0) |
| Xanthurenate | 0.09 (0.05 to 0.13) | 8.9×10−6 | 0.01 (−0.03 to 0.06) | 0.53 | 0.06 (0.03 to 0.09) | 2.2×10−4 | 209 (22) | 93 (15) |
| N-acetylphenylalanine | 0.05 (0.03 to 0.08) | 8.7×10−6 | 0.01 (−0.02 to 0.03) | 0.50 | 0.03 (0.01 to 0.05) | 2.5×10−4 | 1 (0) | 1 (0) |
| Tiglylcarnitine | 0.07 (0.04 to 0.10) | 2.0×10−7 | 0.00 (−0.02 to 0.03) | 0.74 | 0.03 (0.01 to 0.05) | 2.7×10−4 | 6 (1) | 0 (0) |
| Pantothenate | 0.05 (0.03 to 0.07) | 1.7×10−5 | 0.01 (−0.02 to 0.03) | 0.49 | 0.03 (0.01 to 0.05) | 2.8×10−4 | 0 (0) | 0 (0) |
| Serine | 0.00 (−0.01 to 0.01) | 0.96 | 0.02 (0.01 to 0.03) | 2.6×10−6 | 0.01 (0.00 to 0.02) | 3.5×10−4 | 0 (0) | 0 (0) |
| N1-methylinosine | 0.04 (0.02 to 0.06) | 6.0×10−5 | 0.01 (−0.02 to 0.03) | 0.61 | 0.03 (0.01 to 0.04) | 3.6×10−4 | 0 (0) | 7 (1) |
| C-glycosyltryptophan | 0.03 (0.02 to 0.04) | 1.1×10−5 | 0.00 (−0.02 to 0.02) | 0.88 | 0.02 (0.01 to 0.03) | 4.0×10−4 | 0 (0) | 8 (1) |
| Oxalate (ethanedioate) | −0.01 (−0.03 to 0.02) | 0.53 | −0.05 (−0.07 to −0.03) | 2.6×10−5 | −0.03 (−0.04 to −0.01) | 4.5×10−4 | 0 (0) | 0 (0) |
| N-acetylleucine | 0.03 (0.02 to 0.05) | 5.9×10−5 | 0.01 (−0.01 to 0.02) | 0.45 | 0.02 (0.01 to 0.03) | 5.4×10−4 | 1 (0) | 4 (1) |
| N-acetylglutamine | 0.05 (0.03 to 0.08) | 3.3×10−5 | 0.00 (−0.02 to 0.03) | 0.72 | 0.03 (0.01 to 0.05) | 0.001 | 0 (0) | 0 (0) |
| 4-hydroxyhippurate | 0.09 (0.05 to 0.12) | 4.4×10−6 | −0.01 (−0.05 to 0.03) | 0.70 | 0.04 (0.02 to 0.07) | 0.002 | 0 (0) | 7 (1) |
| Creatinine | 0.02 (0.01 to 0.03) | 2.0×10−5 | 0.00 (−0.00 to 0.01) | 0.50 | 0.01 (0.00 to 0.01) | 0.003 | 0 (0) | 0 (0) |
| N-acetylneuraminate | 0.03 (0.02 to 0.04) | 4.5×10−5 | 0.00 (−0.01 to 0.01) | 0.76 | 0.01 (0.00 to 0.02) | 0.004 | 0 (0) | 0 (0) |
| N-acetyl-1-methylhistidine | 0.08 (0.04 to 0.12) | 3.8×10−5 | −0.01 (−0.05 to 0.03) | 0.61 | 0.04 (0.01 to 0.07) | 0.01 | 16 (2) | 3 (0) |
| N6-acetyllysinea | 0.02 (0.01 to 0.03) | 3.0×10−5 | −0.01 (−0.03 to −0.00) | 0.05 | — | — | 0 (0) | 0 (0) |
| Vanillylmandelate (VMA)a | 0.05 (0.03 to 0.07) | 2.1×10−5 | −0.02 (−0.05 to −0.00) | 0.02 | — | — | 3 (0) | 0 (0) |
| 2-methylmalonylcarnitine | 0.10 (0.05 to 0.14) | 1.8×10−5 | −0.01 (−0.03 to 0.01) | 0.34 | 0.01 (−0.01 to 0.03) | 0.32 | 451 (47) | 4 (1) |
Metabolites are ordered by P value in the meta-analysis. Each unit change in β coefficient represents one-fold change (2β−1=100% when β=1) in proteinuria per unit higher log-transformed serum metabolite.
Statistically significant associations are shown in bold. Cut-off for statistical significance in each single study (the AASK or the MDRD study)=0.05/637=7.8×10−5; cut-off for statistical significance in the meta-analysis=0.05/66=7.6×10−4. AASK, African American Study of Kidney Disease and Hypertension; MDRD, Modification of Diet in Renal Disease; 95% CI, 95% confidence interval; GPE, glycero-3-phosphoethanolamine; GPI, glycero-3-phosphoinositol; GPC, glycero-3-phosphocholine.
a
Metabolites with associations opposite in direction across studies were not included in the meta-analysis.