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Kidney Week

Abstract: TH-PO059

Longer-Interval Regimen of Colistin Reduces Nephrotoxicity in Kidney-on-a-Chip

Session Information

Category: Acute Kidney Injury

  • 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

  • Kim, Kipyo, Seoul National University Bundang Hospital, Gyeonggi-do, Korea (the Republic of)
  • Ryu, Ji Young, Seoul National University Bundang Hospital, Gyeonggi-do, Korea (the Republic of)
  • Son, Hyung Eun, 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)
  • Kim, Sejoong, Seoul National University Bundang Hospital, Gyeonggi-do, Korea (the Republic of)
Background

Potential nephrotoxicity of colistin is of growing concerns due to relative high incidence and recent extensive use; however, which dosing regimen is less nephrotoxic remained uncertain. Previous animal and clinical studies have showed conflicting results for less toxic dosing regimen. We investigated whether bolus-mimicking regimens or continuous infusion regimen of colistin may be less nephrotoxic using microfluidic organ-on-a-chip device applying the Pharmakokinetic profile of colistin.

Methods

We introduced colistin to the kidney epithelial cells on kidney-on-a-chips under physiological shear stress condition(1 dyn/cm2) and separated chip devices into two groups: bolus-mimicking regimen group and continuous infusion regimen group. Two drug treatment regimens were given the same total colistin dose over a 48 h period. Bolus-like regimen mimicked pharmacokinetic profiles for human bolus injection with starting colistin concentration of 1138 μg/ml and reducing by half every 9 h known as half-life of colistin in critically ill patients. Continuous Infusion regimen groups were exposed at colistin concentration of 400 μg/ml for 48 h.

Results

The bolus-mimicking regimen injured 1.64% out of total observed cells, whereas the continuous infusion regimen damaged 3.44% after 48-hour colistin exposed period. (P < 0.05). Bolus-mimicking regimen sustained lower transmembrane permeability of FITC-albumin and tight junction protein expression ZO-1 and occludin compared to the prolonged exposed regimen.

Conclusion

We found that a bolus-mimicking regimen dramatically alleviates kidney injury compared to the continuous infused regimen. Longer interval regimens may help to reduce nephrotoxicity in long-term colistin-using patients. In addition, kidney-on-a-chip experiments could be useful for selecting optimal dosing regimen of nephrotoxic drugs.

Figure 1. (A) Two different administration regimen of colistin: Bolus-mimicking regimen and continuous infusion regimen (B) The schematic design of kidney-on-a-chip used in this study

Funding

  • Government Support - Non-U.S.