Abstract: FR-PO140
Measurement Characteristics of Proximal Tubular Secretory Solutes
Session Information
- Molecular Mechanisms of CKD - II
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 1903 CKD (Non-Dialysis): Mechanisms
Authors
- Chen, Yan, University of Washington, Seattle, Washington, United States
- Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
- Zelnick, Leila R., Kidney Research Institute, Seattle, Washington, United States
- Wang, Ke, University of Washington, Seattle, Washington, United States
- Becker, Jessica Osborn, University of Washington, Seattle, Washington, United States
- Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
Background
Reliable measurements of proximal tubular solute clearance, a vital kidney function, have been elusive. We developed targeted liquid chromatographic-tandem mass spectrometric methods to quantify 16 endogenously produced secretory solutes in serum and urine. We tested diurnal variation of each solute, determined their kidney clearances, and assessed associations with the estimated glomerular filtration rate (GFR) in studies of healthy subjects and those with chronic kidney disease (CKD).
Methods
Among healthy controls, we measured plasma concentrations of each solute at 7 time points throughout the day. We calculated 24-hour urinary clearances from timed urine collections using the weighted 24-hour mean plasma value of each solute. We determined the diurnal within-subject coefficient of variation (CV) of plasma concentration for each solute. We investigated associations of derived clearances with estimated GFR in 239 participants from the Seattle Kidney Study, a cohort study of CKD.
Results
Three of the 16 solutes had implausible kidney clearance values and 4 exhibited high diurnal variation (Table). Nine solutes demonstrated reasonable diurnal stability and plausible clearance values. The clearances of these solutes correlated with GFR among CKD patients.
Conclusion
We identified 9 solutes that show promise for estimating proximal tubular secretory clearance - cinnamoylglycine, indoxyl sulfate, p-cresol sulfate, isovalerylglycine, kynurenic acid, pantothenic acid, pyridoxic acid, tiglylglycine, and xanthosine.
| Healthy controls | CKD patients | |||||
| 24h mean plasma concentration (ng/ml) | Within-subject CV of 24h concentration | Clearance (ml/min) | Plasma concentration (ng/ml) | Clearance (ml/min) | Correlation with eGFR | |
| Hippurate | 113.7 | 64.0% | 485 | 239.5 | 521 | 0.361 |
| Cinnamoylglycine | 13.2 | 33.6% | 156 | 31.2 | 76 | 0.267 |
| Indoxyl sulfate | 1475.6 | 27.0% | 34 | 7653.7 | 18 | 0.553 |
| p-cresol sulfate | 15822.0 | 32.2% | 8 | 101683.6 | 4 | 0.508 |
| 3-hydroxyhippurate | 18.6 | 64.5% | 2911 | 40.3 | 2284 | 0.177 |
| Adipic acid | 204.9 | 29.3% | 11 | 260.1 | 14 | 0.049 |
| Dimethyluric acid | 19.2 | 123.5% | 448 | 59.0 | 296 | 0.434 |
| Isovalerylglycine | 5.7 | 32.7% | 351 | 8.0 | 217 | 0.424 |
| Kynurenic acid | 12.6 | 15.6% | 121 | 32.2 | 81 | 0.479 |
| Pantothenic acid | 42.8 | 13.0% | 41 | 93.2 | 24 | 0.350 |
| Pyridoxic acid | 44.7 | 10.6% | 51 | 185.9 | 34 | 0.515 |
| Suberic acid | 305.0 | 26.0% | 0.97 | 889.3 | 0.52 | 0.010 |
| Succinic acid | 1577.8 | 29.8% | 0.62 | 1879.0 | 0.62 | -0.014 |
| Tiglylglycine | 9.1 | 30.8% | 229 | 21.6 | 133 | 0.464 |
| Trimethyluric acid | 2.3 | 73.4% | 380 | 6.2 | 221 | 0.163 |
| Xanthosine | 1.5 | 13.4% | 963 | 15.8 | 305 | 0.276 |
Funding
- NIDDK Support