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Circulating cathepsin-S levels correlate with GFR decline and sTNFR1 and sTNFR2 levels in mice and humans
Tech Univ Munich, Klinikum Rechts Isar, Nephrol Abt, Munich, Germany.
Klinikum Univ Munchen, Div Renal, Med Klin & Poliklin 4, Campus Innenstadt, Munich, Germany.
Klinikum Univ Munchen, Div Renal, Med Klin & Poliklin 4, Campus Innenstadt, Munich, Germany.
Klinikum Univ Munchen, Div Renal, Med Klin & Poliklin 4, Campus Innenstadt, Munich, Germany.
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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
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-316474DOI: 10.1038/srep43538ISI: 000394936800001PubMedID: 28240259OAI: oai:DiVA.org:uu-316474DiVA: diva2:1077913
Funder
EU, Horizon 2020, 668036, 634869Swedish Research CouncilSwedish Heart Lung FoundationMarianne and Marcus Wallenberg Foundation
Available from: 2017-03-01 Created: 2017-03-01 Last updated: 2017-04-03Bibliographically approved

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Larsson, AndersLind, LarsRisérus, UlfCarlsson, Axel CÄrnlöv, Johan
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Biochemial structure and functionCardiovascular epidemiologyClinical Nutrition and MetabolismDepartment of Medical Sciences
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