On the relationship between proteinuria and plasma phosphate.

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Version: author
Serval ID
serval:BIB_39EDDC477103
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
On the relationship between proteinuria and plasma phosphate.
Journal
Swiss medical weekly
Author(s)
de Seigneux S., Wilhelm-Bals A., Courbebaisse M.
ISSN
1424-3997 (Electronic)
ISSN-L
0036-7672
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
147
Pages
w14509
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Albuminuria is strongly associated with renal and cardiovascular outcomes independently of renal function level. However, the pathophysiology of these associations is debated. In chronic kidney disease (CKD), phosphate retention participates in cardiovascular events and increased cardiovascular mortality. We hypothesised that albuminuria may modulate tubular phosphate handling by the kidney. To verify this hypothesis, we first studied the association between phosphataemia and albuminuria in children with nephrotic syndrome and in adults with CKD. In both cases, higher albuminuria was associated with higher phosphate level, independently of glomerular filtration rate. We further tried to decipher the molecular mechanisms of these observations. Using animal models of nephrotic proteinuria, we could show that albuminuric rats and mice had abnormally elevated sodium-phosphate apical co-transporter expression, despite elevated fibroblast growth factor 23 (FGF23). The FGF23 downstream pathway was inhibited despite elevated FGF23 levels. Klotho protein expression was also lower in proteinuric animals compared to controls. Finally, albumin had no direct effects on phosphate transport in cells. Altogether, we show that albuminuria induces alteration of phosphate tubular handling, independently of glomerular filtration rate. The mechanisms involved appear to include Klotho down-regulation and resistance to FGF23. This observation may link albuminuria to increased cardiovascular disease via altered phosphate handling. Finally, this observation opens up further opportunities to better understand the link between albuminuria, Klotho, FGF23 and phosphate handling.
Keywords
Adult, Animals, Cardiovascular Diseases/blood, Cardiovascular Diseases/diagnosis, Child, Disease Models, Animal, Fibroblast Growth Factors, Humans, Mice, Phosphates/blood, Proteinuria/metabolism, Proteinuria/physiopathology, Rats, Renal Insufficiency, Chronic/complications
Pubmed
Web of science
Open Access
Yes
Create date
30/10/2017 12:20
Last modification date
20/08/2019 13:29
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