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doi:10.22028/D291-36753
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: | https://www.sciencedirect.com/science/article/abs/pii/S0085253821006633 |
Link to this record: | urn:nbn:de:bsz:291--ds-367532 hdl:20.500.11880/33394 http://dx.doi.org/10.22028/D291-36753 |
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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