Kidney Week

Abstract: PO1709

Protection of the Remnant Rat Glomeruli from Mechanical Stress Through Structural Adaptation and Pharmacological Intervention After 5/6-Nephrectomy: A Modeling Study

Session Information

• Glomerular Diseases: Fibrosis and Extracellular Matrix
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

• Richfield, Owen, Tulane University Bioinnovation PhD Program, New Orleans, Louisiana, United States

Owen Richfield,

• Cortez, Ricardo, Tulane University Department of Mathematics, New Orleans, Louisiana, United States

Ricardo Cortez,

• Navar, L. Gabriel, Tulane University Department of Physiology, New Orleans, Louisiana, United States

L. Gabriel Navar,

Background

5/6-nephrectomy leads to increased blood flow and pressure in the remaining glomeruli, ultimately resulting in sclerosis. It is hypothesized that these hemodynamic alterations increase mechanical stresses, including shear stress on the glomerular endothelial cells and circumferential hoop stress on podocytes, however these mechanical stresses have not been rigorously quantified. In renoprival conditions glomerular capillary diameters increase, and it is unclear how these structural adaptations affect the mechanical stress magnitudes.

Methods

A mathematical microvascular hemodynamic model was developed to simulate blood flow and plasma filtration on each capillary segment of an anatomically-accurate rat glomerular capillary network. Model parameters were adjusted to match glomerular hemodynamic data for control and 5/6-nephrectomized conditions with and without the presence of the ACE inhibitor, enalapril (Meyer TW et al. Kidney Int. 1987;31(3):752-759). Glomerular capillary diameters were increased according to experimental imaging data (Ferrell, Nicholas, et al. AJP-Renal 308.6 (2015): F588-F593) to simulate glomerular structural adaptations post-5/6-nephrectomy.

Results

Post-5/6-nephrectomy, glomerular capillary structural adaptations reduced mean network shear stress from 156.5 to 92.8 dynes/cm². Without structural adaptations enalapril reduced mean shear stress to 136.1 dynes/cm². The increase in glomerular capillary diameter reduced shear stress while the increased diameters combined with glomerular hypertension increased mean hoop stress from 90.9 to 104.3 kPa. The combination of enalapril and structural adaptations resulted in a mean network shear stress of 81.1 dynes/cm² and hoop stress of 69.7 kPa.

Conclusion

Our results indicate that glomerular structural adaptations protect the glomerular endothelial cells from increased levels of shear stress, thus preserving kidney function. However, these structural adaptations in turn lead to increased hoop stresses. The combination of enalapril with structural adaptations reduces mechanical stress, providing protection and maintaining function for longer periods.

Funding

• NIDDK Support