Abstract: FR-PO761
Effect of Vancomycin on Plasma Concentration of Uremic Solutes
Session Information
- Dialysis: Inflammation and Infection
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 701 Dialysis: Hemodialysis and Frequent Dialysis
Authors
- Soiefer, Leland R., New York University School of Medicine, New York, New York, United States
- Chang, Michelle, New York University School of Medicine, New York, New York, United States
- Tamizuddin, Farah, New York University School of Medicine, New York, New York, United States
- Schatoff, Daria, New York University School of Medicine, New York, New York, United States
- Cofer, Lucas, New York University School of Medicine, New York, New York, United States
- Matalon, Albert, New York University School of Medicine, New York, New York, United States
- Nazzal, Lama, New York University School of Medicine, New York, New York, United States
- Meijers, Bjorn, University Hospitals Leuven, Leuven, Belgium
- Holzman, Robert, New York University School of Medicine, New York, New York, United States
- Lowenstein, Jerome, New York University School of Medicine, New York, New York, United States
Background
Many uremic retention solutes are products of gut bacterial metabolism. Protein-binding renders these solutes poorly dialyzable. In a prior study we observed that a single dose of 250 mg of vancomycin, given by mouth, resulted in a significant (40%) decrease in the plasma concentration of indoxyl sulfate and p-cresyl sulfate over a period of one week. In this study we compared the changes in plasma concentration of a panel of protein-bound uremic retention solutes in response to the once-weekly oral administration of 250 mg of vancomycin or placebo over a period of 8 weeks.
Methods
Eight subjects with chronic, stable ESRD on thrice-weekly hemodialysis via AV fistula in the River Renal Dialysis Unit in Bellevue Hospital, were randomized to two groups, utilizing a single-blinded procedure. Baseline plasma samples were collected prior to the initial dose of vancomycin or placebo and at weeks one, two, three, four, and eight. Uremic retention solutes were measured by MS-HPLC.
Results
Six of the eight uremic retention solutes (Table 1) demonstrated a significant decline in concentration over the eight week period of once-weekly vancomycin administration. The magnitude of the decline makes it more likely that gut production was reduced rather than renal excretion increased. Solute concentrations remained unchanged over the same period of placebo administration.
Conclusion
The significant decline in the plasma concentrations of multiple uremic retention solutes provides evidence of the importance of the gut microbiome in the generation of these solutes. The reduction in concentrations of indoxyl sulfate, p-cresyl sulfate, and kynurenic acid, recognized as likely uremic toxins, suggests that altering the gut microbiome might provide a valuable therapeutic strategy in the management of ESRD.
Linear Trends in Solute Concentrations Over 8 Weeks
| Solute | Placebo | Vancomycin | Change | p-value |
| Hippuric acid | 3.50 | -26.60 | -30.10 | 0.026 |
| Phenyl Acetyl Glutamine | 1.63 | -21.78 | -23.41 | 0.002 |
| p-Cresyl Sulphate | 4.58 | -6.88 | -11.46 | 0.005 |
| Indoxyl Sulphate | 0.15 | -4.56 | -4.71 | 0.053 |
| Kynurenine | 0.03 | -0.15 | -0.18 | 0.015 |
| Kynurenic Acid | 0.03 | -0.08 | -0.11 | 0.005 |
| Phenyl Sulphate | 0.14 | -1.67 | -1.81 | NS |
| Indole-3-Acetic Acid | 0.08 | -0.24 | -0.32 | NS |
Funding
- Private Foundation Support