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Abstract: FR-PO140

Measurement Characteristics of Proximal Tubular Secretory Solutes

Session Information

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 controlsCKD patients
 24h mean plasma concentration (ng/ml)Within-subject CV of 24h concentrationClearance (ml/min)Plasma concentration (ng/ml)Clearance (ml/min)Correlation with eGFR
Hippurate113.764.0%485239.55210.361
Cinnamoylglycine13.233.6%15631.2760.267
Indoxyl sulfate1475.627.0%347653.7180.553
p-cresol sulfate15822.032.2%8101683.640.508
3-hydroxyhippurate18.664.5%291140.322840.177
Adipic acid204.929.3%11260.1140.049
Dimethyluric acid19.2123.5%44859.02960.434
Isovalerylglycine5.732.7%3518.02170.424
Kynurenic acid12.615.6%12132.2810.479
Pantothenic acid42.813.0%4193.2240.350
Pyridoxic acid44.710.6%51185.9340.515
Suberic acid305.026.0%0.97889.30.520.010
Succinic acid1577.829.8%0.621879.00.62-0.014
Tiglylglycine9.130.8%22921.61330.464
Trimethyluric acid2.373.4%3806.22210.163
Xanthosine1.513.4%96315.83050.276

Funding

  • NIDDK Support