Please use this identifier to cite or link to this item: doi:10.22028/D291-36753
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Title: Measurement of urinary Dickkopf-3 uncovered silent progressive kidney injury in patients with chronic obstructive pulmonary disease
Author(s): Schunk, Stefan J.
Beisswenger, Christoph
Ritzmann, Felix
Herr, Christian
Wagner, Martina
Triem, Sarah
Hütter, Gregor
Schmit, David
Zewinger, Stephen
Sarakpi, Tamim
Honecker, Anja
Mahadevan, Peer
Boor, Peter
Wagenpfeil, Stefan
Jörres, Rudolf
Watz, Henrik
Welte, Tobias
Vogelmeier, Claus F.
Gröne, Hermann-Josef
Fliser, Danilo
Speer, Thimoteus
Bals, Robert
Language: English
Title: Kidney International
Volume: 100
Issue: 5
Pages: 1081-1091
Publisher/Platform: Elsevier
Year of Publication: 2021
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Chronic kidney disease (CKD) represents a global public health problem with high disease related morbidity and mortality. Since CKD etiology is heterogeneous, early recognition of patients at risk for progressive kidney injury is important. Here, we evaluated the tubular epithelial derived glycoprotein dickkopf-3 (DKK3) as a urinary marker for the identification of progressive kidney injury in a non-CKD cohort of patients with chronic obstructive pulmonary disease (COPD) and in an experimental model. In COSYCONET, a prospective multicenter trial comprising 2,314 patients with stable COPD (follow-up 37.1 months), baseline urinary DKK3, proteinuria and estimated glomerular filtration rate (eGFR) were tested for their association with the risk of declining eGFR and the COPD marker, forced expiratory volume in one second. Baseline urinary DKK3 but not proteinuria or eGFR identified patients with a significantly higher risk for over a 10% (odds ratio: 1.54, 95% confidence interval: 1.13-2.08) and over a 20% (2.59: 1.28-5.25) decline of eGFR during follow-up. In particular, DKK3 was associated with a significantly higher risk for declining eGFR in patients with eGFR over 90 ml/min/1.73m2 and proteinuria under 30 mg/g. DKK3 was also associated with declining COPD marker (2.90: 1.70-4.68). The impact of DKK3 was further explored in wild-type and Dkk3-/- mice subjected to cigarette smoke-induced lung injury combined with a CKD model. In this model, genetic abrogation of DKK3 resulted in reduced pulmonary inflammation and preserved kidney function. Thus, our data highlight urinary DKK3 as a possible marker for early identification of patients with silent progressive CKD and for adverse outcomes in patients with COPD.
DOI of the first publication: 10.1016/j.kint.2021.06.029
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-367532
ISSN: 0085-2538
Date of registration: 11-Jul-2022
Faculty: M - Medizinische Fakultät
Department: M - Innere Medizin
M - Medizinische Biometrie, Epidemiologie und medizinische Informatik
Professorship: M - Prof. Dr. Robert Bals
M - Prof. Dr. Stefan Wagenpfeil
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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