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Abstract: TH-OR031

Application of 3D Kidney-on-a-Chip for the Evaluation of Contrast-Induced Nephropathy

Session Information

  • Bioengineering
    November 07, 2019 | Location: 146 A/B, Walter E. Washington Convention Center
    Abstract Time: 04:30 PM - 04:42 PM

Category: Bioengineering

  • 300 Bioengineering

Authors

  • Go, Suryeong, Seoul National University Bundang Hospital, Gyeonggi-do, Korea (the Republic of)
  • Kim, Kipyo, Seoul National University Bundang Hospital, Gyeonggi-do, Korea (the Republic of)
  • Yi, Yongjin, Seoul National University Bundang Hospital, Gyeonggi-do, Korea (the Republic of)
  • Jeong, Jong Cheol, Seoul National University Bundang Hospital, Gyeonggi-do, Korea (the Republic of)
  • Kim, Sejoong, Seoul National University Bundang Hospital, Gyeonggi-do, Korea (the Republic of)
  • Chin, Ho Jun, Seoul National University Bundang Hospital, Gyeonggi-do, Korea (the Republic of)
  • Na, Ki Young, Seoul National University Bundang Hospital, Gyeonggi-do, Korea (the Republic of)
  • Chae, Dong-Wan, Seoul National University Bundang Hospital, Gyeonggi-do, Korea (the Republic of)
Background

Among the pathogenic mechanisms of contrast-induced nephropathy (CIN), increased viscosity of concentrated contrast media (CM) in renal tubule can perturb renal hemodynamics and have a detrimental effect on tubular epithelial cells. However, the impacts of viscosity in CIN are still poorly understood. Conventional in vitro culture studies cannot reflect the rheological properties of CM. Therefore, we investigated the effects of CM viscosity on the renal tubule using kidney-on-a-chip and two different types of contrast media.

Methods

Renal proximal tubule epithelial cells (Ronza) were cultured in OrganoPlate (Mimetas), applying time-averaged shear stress of 0.13 dyne/cm2. We treated the cells with two types of CM, low-osmolar agent (iopromide, LOCM) and iso-osmolar agent (iodixanol, IOCM), varying iodine concentrations (50-250mgI/mL). We evaluated cell viability of each group with WST-8 assay. The results of cell viability in Organoplates were compared with those in static conditions. Further, to examine the effects of viscosity-induced renal damage, we increased time-averaged shear stress to 0.52 dyne/cm2. Numerical simulations were also performed with different fluid viscosities.

Results

Overall, increased cell viability was observed under physiological shear stress compared to the static condition. While both LOCM and IOCM decreased cell viability compared with the negative control, LOCM was significantly less viable than IOCM at high concentrations. However, highly increased shear stress resulted in reduced viability in IOCM; no difference between IOCM and LOCM was found under the shear stress of 0.52 dyne/cm2. Numerical simulations revealed that high viscosity slowed the flow rate and augmented fluid shear stress. Viscosity-mediated damage was prominent in high shear stress condition, which may represent CKD conditions with increased single nephron GFR.

Conclusion

CM-induced cytotoxicity was reduced under physiological shear stress compared to static conditions. Nevertheless, under highly increased shear stress, CM viscosity-mediated cytotoxicity was prominent, showing similar viability between IOCM and LOCM.