Abstract: SA-PO614
Renal and Dialytic Clearances of Uremic Solutes
Session Information
- Pharmacology
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Lowenstein, Jerome, New York University Medical Center, New York, New York, United States
- Etinger, Aleksey, New York University Medical Center, New York, New York, United States
- Slater, James, NYU Langone Health, New York, New York, United States
- Meijers, Bjorn, University Hospitals Leuven, Leuven, Belgium
- Holzman, Robert, NYU School of Medicine , New York, New York, United States
Background
Many uremic solutes are protein bound and removed by proximal tubular organic anion transporters (OATs) rather than filtration.
Methods
In 4 subjects undergoing right heart catheterization, samples were obtained from the right renal vein and the inferior vena cava below the renal veins.Total and ultrafiltrate concentrations of uremic solutes were measured utilizing MS-HPLC.
Results
Renal extraction ratio (removal across the renal vascular bed) and renal excretion fraction (renal clearance of solute relative to creatinine) varied greatly. HA and PAG exhibited the highest renal extraction ratios and excretion fractions approximating values reported for para-amino-hippurate (PAH). The dialytic clearance of these solutes exhibited the same pattern but never exceeded estimated creatinine clearance. Highly bound solutes (IS, PCS) exhibited low renal extraction and low renal excretion fractions. KA was an anomaly. Though highly bound, renal extraction and excretion were higher than expected, possibly related to pKa or other unique properties of this solute.
Conclusion
The findings suggest that endogenous hippurate clearance might provide a measure of effective renal plasma flow. The finding that uremic retention solutes such as IS, PCS, and KA, known to bind to OAT receptors on vascular endothelium where they act as transcription factors, are also tightly bound to albumin suggests that protein binding serves to deliver solutes to receptors in a manner analogous to the delivery of hormones, bound to carrier proteins, from an endocrine source to distant receptors.
Protein binding, extraction, and excretion of Uremic Retention Solutes
| Protein Binding | Extraction Ratio | Excretion Fraction | Hemodialyzer Clearance* | |
| Hippuric acid (HA) | 0.68 | 0.79 +/- 0.16** | 4.12 +/- 1.64 | 108 |
| φ acetyl glutamine (PAG) | 0.08 | 0.68 +/- 0.09 | 3.69 +/- 0.65 | 168 |
| Kynurenic acid (KA) | > 0.95*** | 0.43 +/- 0.11 | 2.01 +/- 0.24 | 41 |
| Indoxyl sulfate (IS) | 0.91 | 0.11 +/- 0.20 | 0.72 +/- 0.14 | 26 |
| p-cresyl sulfate (PCS) | 0.92 | 0.06 +/- 0.14 | 0.24 +/- 0.03 | 18 |
| Indole 3 acetic acid (I-3A) | 0.69 | 0.05 +/- 0.12 | 0.08 +/- 0.06 | 70 |
| φ sulfate (PS) | 0.51 | 0.01 +/- 0.13 | 0.28 +/- 0.07 | 49 |
| Kynurenine (KY) | 0.39 | 0.35 +/- 0.07 | 0.01 +/- 0.01 | 96 |
*In ESRD patients(PLoS ONE 13(2): e0192770) **Mean +/- SD *** Minimum estimate based on levels below the limit of detection, 0.002
Funding
- Private Foundation Support