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Cited by 59Renal Diseases and GlomerulopathiesProteoglycans and glycosaminoglycans researchChronic Kidney Disease and Diabetes

The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.

A Synthetic Heparanase Inhibitor Reduces Proteinuria in Passive Heymann Nephritis

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Levidiotis, Vicki, Freeman, Craig, Punler, Malcolm, Martinello, Paul, Creese, Brian, Ferro, Vito, van der Vlag, Johan, Berden, Jo H.M., Parish, Christopher R., Power, David A.·2004·Journal of the American Society of Nephrology
DOI 10.1097/01.asn.0000142426.55612.6d
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Abstract

The beta-D-endoglycosidase heparanase has been proposed to be important in the pathogenesis of proteinuria by acting to selectively degrade the negatively charged side chains of heparan sulfate proteoglycans (HSPG) within the glomerular basement membrane (GBM). A loss of the negatively charged HSPG may result in alteration of the permselective properties of the GBM, loss of glomerular epithelial and endothelial cell anchor points, and liberation of growth factors. This study examined the effect of PI-88, a sulfated oligosaccharide heparanase inhibitor, on renal function, glomerular ultrastructure, and proteinuria. Continuous PI-88 infusion at 25 mg/kg per d did not adversely affect animal behavior, growth, or GFR. Cortical tubular vacuolation, however, was observed by light microscopy, and GBM thickness was significantly reduced in these animals (P < 0.0002). Tissue distribution studies using [(35)S]-labeled PI-88 revealed high levels of radioactivity in the kidney after a single subcutaneous injection of 25 mg/kg, suggesting protracted accumulation; moreover, active PI-88 was detected in urine. In passive Heymann nephritis, PI-88 delivered as a continuous infusion at 25 mg/kg per d significantly reduced autologous-phase proteinuria, at day 14 (P < 0.009), in the absence of altered sheep antibody deposition, C5b-9 deposition, and circulating rat anti-sheep antibody titers. Glomerular vascular endothelial growth factor and fibroblast growth factor expression was unaffected by PI-88 administration. However, PI-88 administration significantly prevented glomerular HSPG loss as demonstrated by quantitative immunofluorescence studies (P < 0.0001) in the absence of altered agrin distribution. These data therefore confirm the importance of heparanase in the development of proteinuria.

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Crossref · 10.1097/01.asn.0000142426.55612.6d

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  • Biological roles of glycans

    Varki, A. (2017) · Glycobiology · doi:10.1093/glycob/cww086 · Cited by 2,635

    “Pathological or experimental damage to such glycans causes large molecules like albumin to escape into the urine, and is associated with glomerular diseases (478, (485) (486) (487) (488) (489) (490) (491) .”
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Metadata

Authors
Levidiotis, V., Freeman, C., Punler, M., Martinello, P., Creese, B., Ferro, V., van der Vlag, J., Berden, J. H. M., Parish, C. R., & Power, D. A.
Affiliations
  • The University of Melbourne (AU)
  • Australian National University (AU)
Corresponding author
  • Levidiotis, Vicki
  • Power, David A.
ORCID
Venue
Journal of the American Society of Nephrology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2004-11
Volume
15
Issue
11
Pages
2882-2892
ISSN
1046-6673 (ISSN-L)
DOI
10.1097/01.asn.0000142426.55612.6d
OpenAlex
W2107149687
Cited by
59
References
45
Citations by year
2025: 2 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 2 · 2013: 4 · 2012: 2
FWCI
4.19
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Journal of the American Society of Nephrology (publishedVersion)
  • PubMed (publishedVersion)
  • ANU Open Research (Australian National University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion, other-oa)
Funders
  • Amgen
  • University of Washington
  • Kidney Health Australia
  • Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Keywords
heparanase, PI-88, heparan sulfate proteoglycans, proteinuria, passive Heymann nephritis, glomerular basement membrane, sulfated oligosaccharides, heparanase inhibitors, glomerular ultrastructure, agrin, endothelial growth factor, fibroblast growth factor, renal function
MeSH terms
Animals, Autoradiography, Fluorescent Antibody Technique, Glomerulonephritis, Immunoglobulin G, Kidney, Kidney Glomerulus, Microscopy, Electron, Oligosaccharides, Proteinuria, Sheep, Complement Membrane Attack Complex, Rats, Sprague-Dawley, Heparan Sulfate Proteoglycans, Rats

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