Kidney Week

Abstract: TH-PO0275

Protein Homeostasis Requires Quiescent Podocytes and Adaptive Mesothelial Cells

Session Information

• Glomerular Diseases: Cell Biology
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Author

• Luke, Robert L., Maine Medical Center - Scarborough Campus, Scarborough, Maine, United States

Robert L. Luke, MD

Background

The permeability of anionic and cationic derivatives of dextran and Ficoll defined a conceptual negative charged homogeneous glomerular barrier. Chemical modification also altered partial draining, a property that conforms with glomerular anatomy in health and its failure in disease.

Methods

Molecular and glomerular models introduced with the permeability of a₁acidglycoprotein, albumin, transferrin, IgG, and a₂macroglobulin in 44 new patients were expanded using histologic measurements and the permeability of albumin, IgG, dextran, and Ficoll in similar cases and the permeability of dextran and Ficoll derivatives in rats. Classic fiber matrix formulation modified for flow dependent solute size yields partial draining depth analogous to Debye shielding length, stratified basement membrane fiber densities, and visceral epithelial shunt. Novel cylindrical model divides glomerulus into filtering capillary and non-filtering mesangium.

Results

Partial draining depths similar to Debye shielding length (9Å) indicate water penetrates and molds Ficoll (8Å), dextran (12Å), and its diethyl amino ethyl derivative (10Å), but not its sulfate derivative (-2Å) because sulfate blocks interaction with water. Reduced non-draining tritiated Ficoll (-2Å) and dextran (2Å) derivatives reveal pliant 29Å +/- 9.4Å slit aperture. Hydraulic pressure increased from 9 to 15 mmHg in slit pore and decreased from 30 to 24 mmHg in basement membrane concomitant with decrease in lamina densa fiber density from 0.20 to 0.14. Protein stranded in lamina rara externa migrates (fiber density 0.03) back across lamina densa supported by mesangium because it is more porous (fiber density 0.10) than lamina densa compressed between endothelium and podocytes. Urinary protein correlated with visceral epithelial shunt that increased from 0.000009 to 0.011 (n=15, r=0.7604, p<0.001) and mesangial volume that increased from 0.47X10⁶mm³ to 1.75 X10⁶mm³ (n=15, r=0.5880, 0.01>p>0.001).

Conclusion

Abnormal podocytes shift hydraulic pressure from basement membrane to slit pore, a dynamic change that increases protein leakage through both regions. Abnormal mesangial cells compromise protein recovery by producing excess matrix or failing to remove protein aggregates such as galactose deficient IgA, immune complexes, or amyloid. Therapy must rehabilitate podocytes and mesangial cells in addition to suppressing production of pathogenic protein.

Acknowledgment

Maine Medical Center Research Department, American Heart Association.

Funding

• Private Foundation Support