title: A model of strain-dependent glomerular basement membrane maintenance and its potential ramifications in health and disease.
abstract: A model is developed and analyzed for type IV collagen turnover in the kidney glomerular basement membrane (GBM), which is the primary structural element in the glomerular capillary wall. The model incorporates strain dependence in both deposition and removal of the GBM, leading to an equilibrium tissue strain at which deposition and removal are balanced. The GBM thickening decreases tissue strain per unit of transcapillary pressure drop according to the law of Laplace, but increases the transcapillary pressure drop required to maintain glomerular filtration. The model results are in agreement with the observed GBM alterations in Alport syndrome and thin basement membrane disease, and the model-predicted linear relation between the inverse capillary radius and inverse capillary thickness at equilibrium is consistent with published data on different mammals. In addition, the model predicts a minimum achievable strain in the GBM based on the geometry, properties, and mechanical environment; that is, an infinitely thick GBM would still experience a finite strain. Although the model assumptions would be invalid for an extremely thick GBM, the minimum achievable strain could be significant in diseases, such as Alport syndrome, characterized by focal GBM thickening. Finally, an examination of reasonable values for the model parameters suggests that the oncotic pressure drop-the osmotic pressure difference between the plasma and the filtrate due to large molecules-plays an important role in setting the GBM strain and, thus, leakage of protein into the urine may be protective against some GBM damage.
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Victor H
authors.initials: VH
authors.lastname: Barocas
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Dorfman
authors.forename: Yoav
authors.initials: Y
authors.lastname: Segal
mesh_terms: D024141:Collagen Type IV / Q000378:metabolism; D050533:Glomerular Basement Membrane / Q000378:metabolism*; D006031:Glycosylation; D006262:Health; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D008954:Models, Biological; D009394:Nephritis, Hereditary / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D024141:Collagen Type IV