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Inverse correlation between vascular endothelial growth factor back-filtration and capillary filtration pressures
Rhein Westfal TH Aachen, Div Nephrol & Immunol, Aachen, Germany.
Rhein Westfal TH Aachen, Inst Heat & Mass Transfer, Aachen, Germany.
Rhein Westfal TH Aachen, Fac Math Informat & Nat Sci, Numer Math, Aachen, Germany.
Rhein Westfal TH Aachen, Div Nephrol & Immunol, Aachen, Germany;Univ Kiel, Dept Nephrol, Kiel, Germany.
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2018 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, no 9, p. 1514-1525Article in journal (Refereed) Published
Abstract [en]

Background: Vascular endothelial growth factor A (VEGF) is an essential growth factor during glomerular development and postnatal homeostasis. VEGF is secreted in high amounts by podocytes into the primary urine, back-filtered across the glomerular capillary wall to act on endothelial cells. So far it has been assumed that VEGF back-filtration is driven at a constant rate exclusively by diffusion.

Methods: In the present work, glomerular VEGF back-filtration was investigated in vivo using a novel extended model based on endothelial fenestrations as surrogate marker for local VEGF concentrations. Single nephron glomerular filtration rate (SNGFR) and/or local filtration flux were manipulated by partial renal mass ablation, tubular ablation, and in transgenic mouse models of systemic or podocytic VEGF overexpression or reduction.

Results: Our study shows positive correlations between VEGF back-filtration and SNGFR as well as effective filtration rate under physiological conditions along individual glomerular capillaries in rodents and humans.

Conclusion: Our results suggest that an additional force drives VEGF back-filtration, potentially regulated by SNGFR.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS , 2018. Vol. 33, no 9, p. 1514-1525
Keywords [en]
endothelium, filtration, GFR, glomerular hypertrophy, VEGF, streaming potential
National Category
Urology and Nephrology
Identifiers
URN: urn:nbn:se:uu:diva-368118DOI: 10.1093/ndt/gfy057ISI: 000446862700006PubMedID: 29635428OAI: oai:DiVA.org:uu-368118DiVA, id: diva2:1267631
Funder
German Research Foundation (DFG), DFG MO 1082/7-1German Research Foundation (DFG), TP04German Research Foundation (DFG), TP17German Research Foundation (DFG), Q2 SFB/Transregio 57Available from: 2018-12-03 Created: 2018-12-03 Last updated: 2018-12-03Bibliographically approved

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Andrae, JohannaBetsholtz, Christer

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