Skip to content

Aldosterone induces albuminuria via matrix metalloproteinase–dependent damage of the endothelial glycocalyx

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)94-107
Number of pages14
JournalKidney International
Issue number1
Early online date31 Oct 2018
DateAccepted/In press - 16 Aug 2018
DateE-pub ahead of print - 31 Oct 2018
DatePublished (current) - Jan 2019


Aldosterone contributes to end-organ damage in heart failure and chronic kidney disease. Mineralocorticoid-receptor inhibitors limit activation of the receptor by aldosterone and slow disease progression, but side effects, including hyperkalemia, limit their clinical use. Damage to the endothelial glycocalyx (a luminal biopolymer layer) has been implicated in the pathogenesis of endothelial dysfunction and albuminuria, but to date no one has investigated whether the glomerular endothelial glycocalyx is affected by aldosterone. In vitro, human glomerular endothelial cells exposed to 0.1 nM aldosterone and 145 mMol NaCl exhibited reduced cell surface glycocalyx components (heparan sulfate and syndecan-4) and disrupted shear sensing consistent with damage of the glycocalyx. In vivo, administration of 0.6 μg/g/d of aldosterone (subcutaneous minipump) and 1% NaCl drinking water increased glomerular matrix metalloproteinase 2 activity, reduced syndecan 4 expression, and caused albuminuria. Intravital multiphoton imaging confirmed that aldosterone caused damage of the glomerular endothelial glycocalyx and increased the glomerular sieving coefficient for albumin. Targeting matrix metalloproteinases 2 and 9 with a specific gelatinase inhibitor preserved the glycocalyx, blocked the rise in glomerular sieving coefficient, and prevented albuminuria. Together these data suggest that preservation of the glomerular endothelial glycocalyx may represent a novel strategy for limiting the pathological effects of aldosterone.

    Research areas

  • aldosterone, albuminuria, endothelium, inflammation, cardiovascular disease

Download statistics

No data available



  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Elsevier at . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 1018 KB, PDF document

    Licence: CC BY-NC-ND


View research connections

Related faculties, schools or groups