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Schurfeld, R.* ; Baalmann, F.* ; Baratashvili, E.* ; Sandner, B.* ; Bachmann, A.* ; Weiner, J.* ; Wurfel, M.* ; Wendt, R.* ; Haussmann, M.* ; Bast, I.* ; Beige, J.* ; Kosacka, J.* ; Klöting-Blüher, N. ; Krohn, K.* ; Kirsten, T.* ; Zhang, M.* ; Harris, R.C.* ; Isermann, B.* ; Kovacs, P.* ; Blüher, M. ; Stumvoll, M.* ; Tonjes, A.* ; Heiker, J.T. ; Ebert, T.*

Inverse association of circulating kallikrein-related peptidase 7 with renal function and mortality risk in patients with chronic kidney disease.

Front. Endocrin. 17:1804956 (2026)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
Introduction Kallikrein-related peptidase 7 (KLK7) is a protease implicated in metabolic disease and obesity. Patients with chronic kidney disease (CKD) exhibit several cardio-metabolic comorbidities and increased mortality. The goal of this study was to investigate the associations of KLK7 levels with renal function and clinical outcomes in patients with CKD.Methods Baseline KLK7 serum levels were cross-sectionally related to renal and cardiometabolic markers in the Leipzig-CKD cohort (n=542). Longitudinal Cox Regression analyses (n=472) were performed to associate baseline circulating KLK7 concentrations and risk of major adverse renal (MARE) and cardiovascular (MACE) events, as well as all-cause mortality. Additionally, mRNA expression of Klk7 and related genes was examined in CKD versus control mice using bulk RNA sequencing.Results KLK7 levels were inversely associated with markers of renal function, i.e. estimated glomerular filtration rate (eGFR), and inflammation, i.e. C-reactive protein, in multivariable regression. Longitudinal analyses associated higher baseline KLK7 with lower all-cause (adjusted HR [95% CI]: 0.65 [0.49-0.86], p=0.003) and non-cardiovascular (adjusted HR [95% CI]: 0.56 [0.40-0.78], p=0.001) mortality over a median follow-up of 7.6 years. A KLK7 threshold of 1383.6 pg/ml stratified patients into low- and high-risk groups for mortality. No associations were found for MARE or MACE. In tissues of CKD and control mice, no significant changes in Klk7 mRNA expression were found.Discussion Circulating KLK7 associates inversely with renal function and inflammation, likely reflecting reduced renal clearance. Higher circulating KLK7 independently predicts lower all-cause mortality, whereas baseline KLK7 was not related to composite renal and CV outcomes.
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Publication type Article: Journal article
Document type Scientific Article
Keywords adipose tissue; chronic kidney disease; dialysis; kallikrein-related peptidase 7; mortality; Corneum Chymotryptic Enzyme; Stratum-corneum; Expression; Serum; Klk7; Progranulin; Prognosis; Protein
ISSN (print) / ISBN 1664-2392
e-ISSN 1664-2392
Journal Frontiers in Endocrinology
Quellenangaben Volume: 17, Issue: , Pages: , Article Number: 1804956 Supplement: ,
Publisher Frontiers
Publishing Place Lausanne
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants Open Access Publishing Fund of Leipzig University
Stockholm, Sweden
Karolinska Institutet Research Foundation
Stiftelsen Stig och Gunborg Westman
Swedish Kidney Foundation (Njurfonden)
German Diabetes Association (DDG)
Otsuka Pharma
European Foundation for the Study of Diabetes Mentorship Programme
AstraZeneca
Medical Faculty of the University of Leipzig
Novo Nordisk