title: Do large pores in the glomerular capillary wall account for albuminuria in nephrotic states?
abstract: Albuminuria in nephrotic states is thought to arise from the formation of large pores in the glomerular capillary wall as large hydrodynamic probes, like Ficoll, have increased fractional clearance. In the present study, we tested for large pore formation in a novel manner. We accounted for the rates of plasma elimination as determined for tritium-labeled tracers of uncharged polydisperse Ficoll (radii range: 35-85 Å) and two globular (14)C-labeled proteins, albumin (radius: 36 Å) and IgG (radius: 55 Å), in control and puromycin aminonucleoside nephrotic (PAN) Sprague-Dawley rats. The plasma elimination rates were then matched to the urinary excretion of these labeled materials (n = 7). Albumin and IgG plasma retention rates were identical and far enhanced compared with the retention rates of inert transport markers of equivalent hydrodynamic radius; their elimination rate corresponded to the elimination of a 75-Å radius Ficoll (n = 5) and >105-Å radius dextran (n = 5). In PAN, they were eliminated as ∼36- and ∼55-Å radii Ficoll, respectively, equivalent to their hydrodynamic radii. In contrast, there was no comparable increase in the elimination rate of Ficoll in PAN. The total plasma clearance of Ficoll in control and PAN rats and the urinary clearance in PAN rats were essentially the same for all radii. On the other hand, the urinary clearance of >45-Å radii Ficoll in controls was considerably lower with increasing radii, demonstrating a postfiltration cellular uptake in controls, which, when inhibited in nephrotic states, would account for apparent large pore formation.
authors.affiliation: Biochemistry Department, Monash University, Clayton, Victoria, Australia; and.
authors.forename: Julijana
authors.initials: J
authors.lastname: Vuchkova
authors.affiliation: Biochemistry Department, Monash University, Clayton, Victoria, Australia; and.
authors.forename: Maria
authors.initials: M
authors.lastname: Koltun
authors.affiliation: Biochemistry Department, Monash University, Clayton, Victoria, Australia; and.
authors.forename: Kerryn
authors.initials: K
authors.lastname: Greive
authors.affiliation: SalAqua Diagnostics, Incorporated, New York, New York wcomper@hotmail.com.
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Comper
mesh_terms: D000419:Albuminuria / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology*; D002250:Carbon Radioisotopes; D002463:Cell Membrane Permeability / Q000502:physiology*; D004195:Disease Models, Animal; D005362:Ficoll; D005919:Glomerular Filtration Rate / Q000502:physiology; D057446:Hydrodynamics; D007074:Immunoglobulin G / Q000652:urine; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000503:physiopathology*; D008297:Male; D009401:Nephrosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D011692:Puromycin Aminonucleoside / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002250:Carbon Radioisotopes; D007074:Immunoglobulin G; D005362:Ficoll; D011692:Puromycin Aminonucleoside
keywords: albumin; glomerular permeability; glomerular transport probes; plasma elimination rate