Association of osteopontin with kidney function and kidney failure in chronic kidney disease patients: the GCKD study
Author:
Steinbrenner Inga1ORCID, Sekula Peggy1ORCID, Kotsis Fruzsina12, von Cube Maja3, Cheng Yurong1, Nadal Jennifer4, Schmid Matthias4, Schneider Markus P5, Krane Vera6, Nauck Matthias78, Eckardt Kai-Uwe5ORCID, Schultheiss Ulla T12, Eckardt Kai-Uwe, Meiselbach Heike, Schneider Markus P, Schiffer Mario, Prokosch Hans-Ulrich, Bärthlein Barbara, Beck Andreas, Reis André, Ekici Arif B, Becker Susanne, Becker-Grosspitsch Dinah, Alberth-Schmidt Ulrike, Hausknecht Birgit, Weigel Anke, Walz Gerd, Köttgen Anna, Schultheiß Ulla T, Kotsis Fruzsina, Meder Simone, Mitsch Erna, Reinhard Ursula, Floege Jürgen, Saritas Turgay, Schaeffner Elke, Baid-Agrawal Seema, Theisen Kerstin, Haller Hermann, Menne Jan, Zeier Martin, Sommerer Claudia, Theilinger Johanna, Wolf Gunter, Busch Martin, Paul Rainer, Sitter Thomas, Wanner Christoph, Krane Vera, Börner-Klein Antje, Bauer Britta, Kronenberg Florian, Raschenberger Julia, Kollerits Barbara, Forer Lukas, Schönherr Sebastian, Weissensteiner Hansi, Oefner Peter, Gronwald Wolfram, Schmid Matthias, Nadal Jennifer,
Affiliation:
1. Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center–University of Freiburg , Freiburg , Germany 2. Department of Medicine IV–Nephrology and Primary Care, Faculty of Medicine and Medical Center–University of Freiburg , Freiburg , Germany 3. Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center–University of Freiburg , Freiburg , Germany 4. Department of Medical Biometry, Informatics and Epidemiology, Faculty of Medicine, University of Bonn , Bonn , Germany 5. Department of Nephrology and Hypertension, University Hospital Erlangen , Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen , Germany 6. Department of Internal Medicine I, Division of Nephrology, University Hospital Würzburg , Würzburg , Germany 7. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald , Greifswald , Germany 8. DZHK (German Center for Cardiovascular Research) , partner site Greifswald, Greifswald , Germany
Abstract
ABSTRACT
Background
Osteopontin (OPN), synthesized in the thick ascending limb of Henle's loop and in the distal tubule, is involved in the pathogenesis of kidney fibrosis, a hallmark of kidney failure (KF). In a cohort of chronic kidney disease (CKD) patients, we evaluated OPN's association with kidney markers and KF.
Methods
OPN was measured from baseline serum samples of German Chronic Kidney Disease study participants. Cross-sectional regression models for estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) as well as Cox regression models for all-cause mortality and KF were evaluated to estimate the OPN effect. Additionally, the predictive ability of OPN and time-dependent population-attributable fraction were evaluated.
Results
Over a median follow-up of 6.5 years, 471 KF events and 629 deaths occurred among 4950 CKD patients. One-unit higher log(OPN) was associated with 5.5 mL/min/1.73 m2 lower eGFR [95% confidence interval (95% CI) –6.4 to –4.6] and 1% change in OPN with 0.7% higher UACR (estimated effect 0.7, 95% CI 0.6–0.8). Moreover, higher OPN levels were associated with a higher risk of KF [hazard ratio (HR) 1.4, 95% CI 1.2–1.7] and all-cause mortality (HR 1.5, 95% CI 1.3–1.8). After 6 years, 31% of the KF events could be attributed to higher OPN levels (95% CI 3%–56%).
Conclusions
In this study, higher OPN levels were associated with kidney function markers worsening and a higher risk for adverse outcomes. A larger proportion of KF could be attributed to higher OPN levels, warranting further research on OPN with regards to its role in CKD progression and possible treatment options.
Publisher
Oxford University Press (OUP)
Subject
Transplantation,Nephrology
Cited by
10 articles.
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