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Kidney Week

Abstract: PO2377

Clinically Apparent AKI Secondary to Suspected Vancomycin Toxicity: A Cellular Kinetic Analysis

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Flood, Ryan P., University of Colorado Denver School of Medicine, Aurora, Colorado, United States
  • Ray, Matthew, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
  • Blaine, Judith, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
  • Bansal, Anip, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
Background

The use of antimicrobial therapies for treatment of hospitalized patients is abundant. While the usage rate of antibiotics has remained stable over the last decade, however, with the emergence of methicillin-resistant staphylococcus aureus, vancomycin usage has increased during that same time period. Although vancomycin induced AKI or vancomycin associated nephrotoxicity (VAN) has been a topic of debate since its generalized use approximately 50 years ago, the proposed mechanism of VAN is an on-going focus of research.
The current study aims to answer whether proximal tubular creatinine secretion, which can account for upwards of 20% of creatinine clearance, is impacted by vancomycin dosing, and whether vancomycin trough levels seen in clinical practice alter this relationship.

Methods

For the cellular kinetic analysis, we took immortalized human proximal tubule epithelial cells, and after allowing them to epithelialize on a semi-permeable membrane, evaluated creatinine secretion in the presence of varying concentrations of both creatinine and vancomycin, while measuring eliminated levels for up to 24 hours.
For the patient analysis, IRB approval was obtained to evaluate the cases of possible VAN on the renal consult service.

Results

Creatinine secretion through the cellular epithelium was not affected by vancomycin at levels up to 4X therapeutic, the upper limit of those seen on a cohort of patients in the renal consult service at the university of Colorado. This is consistent with other pharmacokinetic date, indicating that vancomycin is able to inhibit tranporters of creatinine, but at levels not seen in clinical practice.
The patient cohort analysis identified thirteen patients who were deemed to have "possible VAN," and in all of these the rise in Cr did happen temporally related to vancomycin, and there were many other factors potentially confounding their AKI.

Conclusion

Proximal tubule dysfunction from vancomycin inhibition of cellular transporters does not cause creatinine elevation in concentrations used clinically. The cases of clinically apparent vancomycin associated nephrotoxicity are multifactorial. Therefore the nephrotoxocity associated with vancomycin administration does not seem to be the sole cause of creatinine elevation in patients with AKI.