ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO764

Pathophysiology of Proteinuria: Human Serum Increases Proliferation and Markers of AKI in an Ex Vivo Model of the Human Proximal Tubule

Session Information

  • Bioengineering
    October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Bioengineering

  • 300 Bioengineering

Authors

  • Patel, Ranita S., Seattle Children's Hospital, Seattle, Washington, United States
  • Lidberg, Kevin, University of Washington, Seattle, Washington, United States
  • Yeung, Catherine K., University of Washington, Seattle, Washington, United States
  • Himmelfarb, Jonathan, Kidney Research Institute, Seattle, Washington, United States
  • Kelly, Edward J., University of Washington, Seattle, Washington, United States
Background

Proteinuria is a pathological cause for progressive kidney damage. Prolonged exposure to excess glomerular filtered protein may create tubulointerstitial lesions via activation of proinflammatory, proapoptotic, and profibrotic pathways in renal proximal tubular cells[1]. Thus the proximal tubule likely plays an important role in propagating the decline of renal function in proteinuric kidney disease[2].

Methods

Here, we exposed a 3D microphysiological system (MPS) of the human kidney proximal tubule developed in our lab[3] to human serum to explore key functional and structural events that may eventually lead to progressive tubulointerstitial damage. This is a bioengineered platform containing a tubular collagen scaffold that houses human proximal tubule cells. Perfusion setup allows for the delivery of media and experimental solutions, as well as physiological shear stress applied to the cellular tubule.

Results

Treatment with 0.5%, 1%, and 2% human serum for 48 hours led to an increase in kidney injury molecule 1 (KIM-1) concentrations measured from MPS effluents, with an average 3.55 fold increase in the 2% human serum group. The percent of cells expressing the proliferation marker Ki67 dramatically increased with ascending concentrations of human serum (8% in control vs 38% in 2 percent human serum).

Conclusion

These data demonstrate that proximal tubule cells exposed to proteins contained in human serum shed KIM-1 (a urinary biomarker of acute kidney injury) and undergo a burst of proliferation, perhaps as a compensatory mechanism or as an initiative to begin tubular wound healing. Future efforts will include prolonging exposure times, quantifying injury-associated microRNAs, and performing transcriptomic profiling with RNA sequencing to reveal novel biomarkers or pathways involved in proteinuric pathophysiology.

Funding

  • Other NIH Support