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- Dokumenttyp:
- Journal Article; Article
- Autor(en):
- Steubl, Dominik; Kumar, Santhosh V; Tato, Maia; Mulay, Shrikant R; Larsson, Anders; Lind, Lars; Risérus, Ulf; Renders, Lutz; Heemann, Uwe; Carlsson, Axel C; Ärnlöv, Johan; Anders, Hans-Joachim
- Titel:
- Circulating cathepsin-S levels correlate with GFR decline and sTNFR1 and sTNFR2 levels in mice and humans.
- Abstract:
- 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.
- Zeitschriftentitel:
- Sci Rep
- Jahr:
- 2017
- Band / Volume:
- 7
- Seitenangaben Beitrag:
- 43538
- Sprache:
- eng
- Volltext / DOI:
- doi:10.1038/srep43538
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/28240259
- Print-ISSN:
- 2045-2322
- TUM Einrichtung:
- Fachgebiet Nephrologie (Prof. Heemann)
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