Table 3.
Associations between kidney clearances of secretory solutes and CKD progression
| Solute | Unadjusted | Model 1a | Model 2b | |||
|---|---|---|---|---|---|---|
| HR (95% CI)c | P Value | HR (95% CI)c | P Value | HR (95% CI)c | P Value | |
| Hippurate | 1.15 (1.11 to 1.18) | <0.001d | 0.99 (0.95 to 1.03) | 0.61 | 1.01 (0.97 to 1.05) | 0.74 |
| Pyridoxic acid | 1.53 (1.46 to 1.60) | <0.001d | 1.18 (1.11 to 1.26) | <0.001d | 1.18 (1.10 to 1.26) | <0.001d |
| Dimethyluric acid | 1.17 (1.13 to 1.22) | <0.001d | 1.03 (0.99 to 1.07) | 0.21 | 1.03 (0.99 to 1.07) | 0.21 |
| Trimethyluric acid | 1.19 (1.15 to 1.23) | <0.001d | 1.03 (0.99 to 1.07) | 0.16 | 1.03 (0.99 to 1.07) | 0.12 |
| Isovalerylglycine | 1.51 (1.43 to 1.59) | <0.001d | 1.16 (1.08 to 1.24) | <0.001d | 1.13 (1.05 to 1.21) | 0.001d |
| Tiglylglycine | 1.45 (1.38 to 1.52) | <0.001d | 1.08 (1.01 to 1.14) | 0.02 | 1.06 (1.00 to 1.13) | 0.05 |
| Kynurenic acid | 1.73 (1.62 to 1.84) | <0.001d | 1.24 (1.13 to 1.35) | <0.001d | 1.21 (1.10 to 1.32) | <0.001d |
| Xanthosine | 1.35 (1.29 to 1.42) | <0.001d | 1.10 (1.05 to 1.16) | <0.001d | 1.13 (1.08 to 1.19) | <0.001d |
| Cinnamoylglycine | 1.26 (1.21 to 1.32) | <0.001d | 1.11 (1.06 to 1.17) | <0.001d | 1.11 (1.06 to 1.17) | <0.001d |
| Indoxyl sulfate | 1.69 (1.60 to 1.79) | <0.001d | 1.17 (1.08 to 1.26) | <0.001d | 1.15 (1.06 to 1.24) | <0.001d |
| p-Cresol sulfate | 1.34 (1.29 to 1.39) | <0.001d | 1.08 (1.02 to 1.15) | 0.01 | 1.08 (1.01 to 1.16) | 0.02 |
| Summary score | 1.97 (1.84 to 2.11) | <0.001d | 1.27 (1.15 to 1.39) | <0.001d | 1.28 (1.16 to 1.41) | <0.001d |
Total n=3207. CKD progression defined as 50% decline in eGFRCRIC from baseline, initiation of chronic dialysis, or kidney transplantation over follow-up. Results from the Cox proportional hazard model. HR, hazard ratio; CI, confidence interval; eGFRCRIC, glomerular filtration rate estimated based on serum creatinine and cystatin C concentrations, age, sex, and Black race using an equation that was developed in a subcohort of 1433 CRIC participants who underwent 125-Iothalamate GFR clearance studies.
Model 1 adjusted for age, race, sex, eGFRCRIC, and log-transformed 24-h urinary albumin excretion.
Model 2 additionally adjusted for clinical site, BMI, diabetes, smoking status, systolic BP, any cardiovascular disease, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.
Hazard ratio expressed per 50% lower secretory-solute clearance or per 10-unit lower summary secretion score.
Statistically significant after correction for multiple comparisons using the Hommel method.