Evidence map›Paper›PMID 30389198›Full record

ArticleKidney international2019

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

Matthew J Butler, Raina Ramnath, Hiroyuki Kadoya, Dorinne Desposito, Anne Riquier-Brison, Joanne K Ferguson, Karen L Onions, Anna S Ogier, Hesham ElHegni, Richard J Coward and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Kidney international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
5.3field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 89 citations in OpenAlex.

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  3. Renalase stimulates aldosterone production via PMCA4b/cAMP in NCI-H295R cells.Journal of enzyme inhibition and medicinal chemistry · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Matthew J ButlerBristol Renal, Bristol Medical School, University of Bristol, Bristol, UK. Electronic address: Matthew.Butler@bristol.ac.uk.
Raina RamnathBristol Renal, Bristol Medical School, University of Bristol, Bristol, UK.
Hiroyuki KadoyaDepartment of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Dorinne DespositoDepartment of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Anne Riquier-BrisonDepartment of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Joanne K FergusonBristol Renal, Bristol Medical School, University of Bristol, Bristol, UK.
Karen L OnionsBristol Renal, Bristol Medical School, University of Bristol, Bristol, UK.
Anna S OgierBristol Renal, Bristol Medical School, University of Bristol, Bristol, UK.
Hesham ElHegniBristol Renal, Bristol Medical School, University of Bristol, Bristol, UK.
Richard J CowardBristol Renal, Bristol Medical School, University of Bristol, Bristol, UK.
Gavin I WelshBristol Renal, Bristol Medical School, University of Bristol, Bristol, UK.
Rebecca R FosterBristol Renal, Bristol Medical School, University of Bristol, Bristol, UK.
Janos Peti-PeterdiDepartment of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Simon C SatchellBristol Renal, Bristol Medical School, University of Bristol, Bristol, UK.
University of Bristol · GBUniversity of Southern California · USAt Bristol · GB

Funding

Multiphoton Imaging of the Juxtaglomerular ApparatusR01DK064324 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JANOS PETI-PETERDI · 2004 to 2026
$8.4M
Multiphoton microscope replacement for USC shared resourceS10OD021833 · OD · UNIVERSITY OF SOUTHERN CALIFORNIA · PI PETI-PETERDI, JANOS · 2017 to 2017
$600k
Biotechnology and Biological Sciences Research Council BB/G012776/1Medical Research Council MR/K010492/1Medical Research Council MR/M018237/1NIDDK NIH HHS R01 DK064324NIH HHS S10 OD021833
6 · The paper itself

Abstract

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.

Indexed as

AlbuminuriaAldosteroneAnimalsCell LineDisease Models, AnimalEndothelial CellsGlycocalyxHeparan SulfateHumansKidney GlomerulusMaleMatrix Metalloproteinase 2Matrix Metalloproteinase 9Matrix Metalloproteinase InhibitorsMiceMice, Inbred C57BLAldosteroneHeparan SulfateMatrix Metalloproteinase 2Matrix Metalloproteinase 9Matrix Metalloproteinase InhibitorsMmp2 protein, mouseMmp9 protein, mouseSdc4 protein, mouseSodium ChlorideSyndecan-4albuminuriaaldosteronecardiovascular diseaseendotheliuminflammation

Identifiers

PMID30389198
PMCPMC6506575
OpenAlexW2899317753

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.