Kidney Week

Abstract: TH-PO0034

Inhibitory Effects of Dapagliflozin on Human Renal Proximal Tubular Epithelial Cells Encapsulated Within a Bioartificial Nephron

Session Information

• Bioengineering: MPS, Flow, and Delivery
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bioengineering

• 400 Bioengineering

Authors

• Torres, Alonso, University of California San Francisco, San Francisco, California, United States

Alonso Torres

• Vo, Noelle, University of California San Francisco, San Francisco, California, United States

Noelle Vo, PharmD

• Spencer, Mason, Claremont McKenna College, Claremont, California, United States

Mason Spencer

• Zagorov, Alberta, University of California San Francisco, San Francisco, California, United States

Alberta Zagorov

• Guan, Deanna, University of California San Francisco, San Francisco, California, United States

Deanna Guan

• Brakeman, Paul R., University of California San Francisco, San Francisco, California, United States

Paul R. Brakeman, MD, PhD

• Fissell, William Henry, Vanderbilt University, Nashville, Tennessee, United States

William Henry Fissell, MD

• Roy, Shuvo, University of California San Francisco, San Francisco, California, United States

Shuvo Roy, PhD

Background

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are commonly prescribed to T2DM and CKD patients. Our group has developed a biomimetic device combining renal tubular epithelial cells (RPTEC) with silicon nanopore membranes (SNM) to recapitulate nephron architecture. We have used the bioartificial nephron (BAN) to characterize the reabsorption of glucose in ultrafiltrate by human RPTEC and resulting inhibitory effects of an SGLT2 inhibitor drug, dapagliflozin (DPG).

Methods

Transwell membranes were seeded at a density of 500,000 RPTEC/cm² and were exposed to 6mM glucose or 28mM glucose under static or dynamic shear stress (OSS, 1 dyne/cm²). Glucose reabsorption was measured with DPG administered at 0,15, and 45 ng/ml concentrations against controls. BAN devices (N=3) were built using polycarbonate housings precisely machined to incorporate SNM and RPTEC-constructs. A mock flow loop generated ultrafiltrate in the BAN exposing the encapsulated RPTEC to 6 mM glucose for 60 minutes, 28mM glucose for 30 minutes, and then 15 ng/mL of DPG was infused into the loop concurrent with 28mM glucose. The apical ultrafiltrate and basal fluids were sampled and the corresponding glucose concentrations measured by glucometer. Live/dead cell viability was assessed with ReadyProbes^TM cell viability imaging kits. GraphPad Prism was used data analysis with ANOVA one and two-way tests to assess statistical significance.

Results

Cell viability of RPTEC on transwell membranes declined under continuous OSS by 25% and with 45 ng/ml of DPG by 35% when exposed to 6mM glucose concentrations compared to static control and medication. However, RPTEC maintained higher viability (above 70%) in the dynamic setting with 28mM glucose conditions (p < 0.01) compared to static transwell controls. In the BAN, the drug's effect on RPTEC glucose reabsorption was reduced in hyperglycemic conditions by up to 30% within 90 minutes of administration.

Conclusion

The BAN exhibited SGLT2-dependent glucose reabsorption, which was responsive to pharmacological inhibition. Future directions will assess chemical barrier performance and GLUT2 expression. Ultimately, scaling up the cell mass within the BAN could lead to an ambulatory device with clinical-scale potential to assist in glycemic control.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025b5m81g6m