du.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Circulating cathepsin-S levels correlate with GFR decline and sTNFR1 and sTNFR2 levels in mice and humans
Show others and affiliations
Number of Authors: 12
2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 43538Article in journal (Refereed) Published
Abstract [en]

Cardiovascular complications determine morbidity/mortality in chronic kidney disease (CKD). We hypothesized that progressive CKD drives the release of cathepsin-S (Cat-S), a cysteine protease that promotes endothelial dysfunction and cardiovascular complications. Therefore, Cat-S, soluble tumor-necrosis-factor receptor (sTNFR) 1/2 and glomerular filtration rate (GFR) were measured in a CKD mouse model, a German CKD-cohort (MCKD, n = 421) and two Swedish community-based cohorts (ULSAM, n = 764 and PIVUS, n = 804). Association between Cat-S and sTNFR1/2/GFR was assessed using multivariable linear regression. In the mouse model, Cat-S and sTNFR1/2 concentrations were increased following the progressive decline of GFR, showing a strong correlation between Cat-S and GFR (r = -0.746, p < 0.001) and Cat-S and sTNFR1/sTNFR2 (r = 0.837/0.916, p < 0.001, respectively). In the human cohorts, an increase of one standard deviation of estimated GFR was associated with a decrease of 1.008 ng/ml (95%-confidence interval (95%-CI) -1.576-(-0.439), p < 0.001) in Cat-S levels in MCKD; in ULSAM and PIVUS, results were similar. In all three cohorts, Cat-S and sTNFR1/sTNFR2 levels were associated in multivariable linear regression (p < 0.001). In conclusion, as GFR declines Cat-S and markers of inflammation-related endothelial dysfunction increase. The present data indicating that Cat-S activity increases with CKD progression suggest that Cat-S might be a therapeutic target to prevent cardiovascular complications in CKD.

Place, publisher, year, edition, pages
2017. Vol. 7, 43538
Keyword [en]
chronic kidney disease; prognostic markers
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
URN: urn:nbn:se:du-24488DOI: 10.1038/srep43538ISI: 000394936800001PubMedID: 28240259OAI: oai:DiVA.org:du-24488DiVA: diva2:1078384
Available from: 2017-03-03 Created: 2017-03-03 Last updated: 2017-03-27Bibliographically approved

Open Access in DiVA

fulltext(4183 kB)14 downloads
File information
File name FULLTEXT01.pdfFile size 4183 kBChecksum SHA-512
16f97a447fa5bcf07568ae3134e5a39da112cb1bd800fceb45ce73170638c0f57ef7a0f51f3e268430d94e2bba9b38bdf8acf9c0656d830aee10cbe713bf0778
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Ärnlöv, Johan
By organisation
Medical Science
In the same journal
Scientific Reports
Clinical Medicine

Search outside of DiVA

GoogleGoogle Scholar
Total: 14 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 241 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf