Circulating cathepsin-S levels correlate with GFR decline and sTNFR1 and sTNFR2 levels in mice and humans.

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

doi:10.1038/srep43538

Klinik und Poliklinik für Innere Medizin II, Gastroenterologie (Prof. Schmid)

Back
Back to start of result list
Permanent link for displayed object

Title:: Circulating cathepsin-S levels correlate with GFR decline and sTNFR1 and sTNFR2 levels in mice and humans.
Document type:: Journal Article; Article
Author(s):: 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
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.
Journal title abbreviation:: Sci Rep
Year:: 2017
Journal volume:: 7
Pages contribution:: 43538
Language:: eng
Fulltext / DOI:: doi:10.1038/srep43538
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/28240259
Print-ISSN:: 2045-2322
TUM Institution:: Fachgebiet Nephrologie (Prof. Heemann)
BibTeX

Occurrences:

mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments

mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Innere Medizin II, Gastroenterologie (Prof. Schmid)Abteilung für Nephrologie (Prof. Heemann)Professur für Nephrologie (Prof. Heemann)2017