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Abstract: SA-PO019

A Microfluidic Approach for Cardiovascular Risk Stratification in CKD and ESKD Patients

Session Information

Category: Bioengineering

  • 400 Bioengineering

Authors

  • Rathod, Mitesh, UNC Chapel Hill, Chapel Hill, North Carolina, United States
  • Aw, Wen Yih, UNC Chapel Hill, Chapel Hill, North Carolina, United States
  • Doherty, Elizabeth L., UNC Chapel Hill, Chapel Hill, North Carolina, United States
  • Xi, Gang, UNC Chapel Hill, Chapel Hill, North Carolina, United States
  • Roy-Chaudhury, Prabir, UNC Chapel Hill, Chapel Hill, North Carolina, United States
  • Polacheck, William J., UNC Chapel Hill, Chapel Hill, North Carolina, United States
Background

Cardiovascular (CV) complications are responsible for over 50% of the overall morbidity and mortality in CKD and ESKD patients. Surprisingly, conventional cardiovascular risk factors such as hyperlipidemia and obesity are not as predictive of CV complications in the CKD/ESKD population as compared to the general population and statins in particular do not reduce CV events in hemodialysis patients. This so called “reverse epidemiology” is thought to reflect a primacy of uremia induced vascular dysfunction in the pathogenesis of CV complications in this unique patient population. In order to develop novel, real world and holistic markers of uremia induced inflammation, oxidative stress and endothelial dysfunction, we herein report a 3D microfluidic device to quantify the negative effects of uremic serum on endothelial cells.

Methods

HUVECs were seeded in cylindrical channels in collagen I hydrogels to form microvessels (Fig. 1). After 48 h, perfusion media was exchanged from cell culture media to 100% human serum for 24 hours. To mimic the uremic environment, we added pathophysiological levels of indoxyl sulfate (IS) to serum from healthy donors (Fig 1A-B).

Results

Microvessels perfused with serum from healthy donors exhibited distinct, pericellular VE-cadherin staining, while microvessels perfused with serum containing IS displayed diffuse VE-cadherin indicating immature or dysfunctional adherens junction integrity (Fig. 1A). Consistent with these observations, microvessels perfused with serum containing IS exhibited marked increase in solute permeability compared to microvessels perfused with healthy serum (Fig. 1B).

Conclusion

These results demonstrate a humanized microfluidic device that can be used to assess endothelial dysfunction in response to uremic toxins. We demonstrate high sensitivity of the assay, as IS at concentrations similar to those for CKD-3 patients resulted in significant cytoskeletal and permeability defects, suggesting that this platform could be used to screen for CV risk in CKD/ESKD patients.