Charge Selective Function in Childhood Glomerular Diseases

Takahashi, Shori; Watanabe, S; Wada, Naohiro; Murakami, Hitohiko; Funaki, Satoshi; Kou, Yan; Kondo, Yoshiaki; Harada, Kensuke; Nagata, Michio

doi:10.1203/01.pdr.0000196733.47083.81

Cited by 8 publications

(6 citation statements)

References 39 publications

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“…Data from early studies exploring GBM permeability provide compelling evidence in support this concept, demonstrating that anionic charge does establish an electrostatic barrier that hinders/constrains the flux of polycationic solutes across the GBM (Chang et al, 1975; Rennke et al, 1975; Brenner et al, 1977, 1978; Deen et al, 1977; Rennke & Venkatachalam, 1977). In extrapolating that conceptual function to explain pathophysiologic events seen in disease, it was logical to surmise that the loss of GBM anionic charge would develop in diseases/disease models in which proteinuria occurs (Ala-Houhala & Pasternack, 1987; Okada et al, 1989; Wada et al, 1990; Gambaro et al, 1992; Morano et al, 1993; Fox et al, 1994; Morano et al, 1994; Goode et al, 1995; van den Born et al, 1995; Raats et al, 2000; Sakagami et al, 2004; Takahashi et al, 2006). Although the GBM has both size and charge selectivity, the molecular weight cutoff for the barrier is still a highly contested issue in the field of renal function (Singh et al, 2011).…”

Section: The Glomerular Basement Membrane—a Unique Basal Laminamentioning

confidence: 99%

The Glomerular Basement Membrane as a Model System to Study the Bioactivity of Heparan Sulfate Glycosaminoglycans

McCarthy

Wassenhove-McCarthy

2012

Microsc Microanal

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The glomerular basement membrane and its associated cells are critical elements in the renal ultrafiltration process. Traditionally the anionic charge associated with several carbohydrate moieties in the glomerular basement membrane are thought to form a charge selective barrier that restricts the transmembrane flux of anionic proteins across the glomerular basement membrane into the urinary space. The charge selective function, along with the size selective component of the basement membrane, serves to limit the efflux of plasma proteins from the capillary lumen. Heparan sulfate glycosaminoglycans are anionically charged carbohydrate structures attached to proteoglycan core proteins and have a role in establishing the charge selective function of the glomerular basement membrane. Although there are a large number of studies in the literature that support this concept, the results of several recent studies using molecular genetic approaches to minimize the anionic charge of the glomerular basement membrane would suggest that the role of heparan sulfate glycosaminoglycans in the glomerular capillary wall are still not yet entirely resolved, suggesting that this research area still requires new and novel exploration.

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Section: The Glomerular Basement Membrane—a Unique Basal Laminamentioning

confidence: 99%

The Glomerular Basement Membrane as a Model System to Study the Bioactivity of Heparan Sulfate Glycosaminoglycans

McCarthy

Wassenhove-McCarthy

2012

Microsc Microanal

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“…This suggests that the charge barrier function is operating at a lower level in IgAN than in SSNS. Based on these results, the clearance ratio between IgG and IgA, which are roughly equal in effective radius but different in charge, was used as a CSI [6]. In the present study, the CSI was the highest in the CGN group, lower in the PD group and the lowest in the Dent disease group.…”

Section: Discussionmentioning

confidence: 79%

“…Definition of CSI Serum and urinary IgA and IgG were measured by latex methods described elsewhere [6]. Urinary IgA in Dent disease patients, which was under the sensitivity limit of the latex methods, was measured by enzyme-linked immunosorbent assay (ELISA) using rabbit antisera against human IgA (α chain; Dako, Glostrup, Denmark) and horseradish peroxidase-conjugated rabbit antisera against human IgA (Dako).…”

Section: Methodsmentioning

confidence: 99%

“…Urinary IgA in Dent disease patients, which was under the sensitivity limit of the latex methods, was measured by enzyme-linked immunosorbent assay (ELISA) using rabbit antisera against human IgA (α chain; Dako, Glostrup, Denmark) and horseradish peroxidase-conjugated rabbit antisera against human IgA (Dako). CSI was the renal clearance ratio between IgG (Stokes-Einstein radius 49-60 Å, pI 4.5-9.0) and IgA (Stokes-Einstein radius 61 Å, pI 3.5-5.5), which are roughly equal in effective radius but significantly different in charge [6].…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, the charge barrier function of the endothelial cell surface layer and the GBM needed reexamination. Here, the charge barrier function has been evaluated using a charge selectivity index (CSI) [6] in patients with podocyte disease (PD), chronic glomerulonephritis (CGN), and Dent disease. The urinary protein constitution in Dent disease was assumed to comprise a normal glomerular filtrate concentrate [7].…”

Section: Introductionmentioning

confidence: 99%

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Reevaluation of glomerular charge selective protein-sieving function

et al. 2009

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Recently, disorders of the slit diaphragm have been considered as major causes of proteinuria in renal disease and the charge barrier function of the glomerular capillary wall has been given less attention. We evaluated the charge selectivity index (CSI) in 40 patients with podocyte disease (PD), 75 with chronic glomerulonephritis (CGN), and 8 with Dent disease, to reexamine the charge barrier function. We evaluated CSI in Dent disease because the urinary protein profile in Dent disease was assumed to be a concentrate of a normal glomerular filtrate. CSI was defined as the renal clearance ratio between IgA and IgG. CSI values (mean +/- SD) in the CGN and PD groups and in Dent disease were 1.12 +/- 0.25, 0.42 +/- 0.31, and 0.16 +/- 0.06, respectively, suggesting that the charge barrier function was defective in the CGN group and of reduced capacity in the PD group. The results suggest that functional interactions between the slit diaphragm and the glomerular basement membrane exist, and that a slit diaphragm disorder is accompanied by a decrease in the charge barrier function in PD, as argued by the conventional hypothesis.

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Hematuria and Proteinuria

Yap

Lau²

2023

Pediatric Kidney Disease

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Charge Selective Function in Childhood Glomerular Diseases

Cited by 8 publications

References 39 publications

The Glomerular Basement Membrane as a Model System to Study the Bioactivity of Heparan Sulfate Glycosaminoglycans

The Glomerular Basement Membrane as a Model System to Study the Bioactivity of Heparan Sulfate Glycosaminoglycans

Reevaluation of glomerular charge selective protein-sieving function

Hematuria and Proteinuria

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