Association of osteopontin with kidney function and kidney failure in chronic kidney disease patients: the GCKD study
Inga Steinbrenner, Peggy Sekula, Fruzsina Kotsis, Maja von Cube, Yurong Cheng, Jennifer Nadal, Matthias Schmid, Markus P. Schneider, Vera Krane, Matthias Nauck, Kai-Uwe Eckardt, Ulla T. Schultheiß, the GCKD investigators, Kai-Uwe Eckardt, Heike Meiselbach, Markus P Schneider, Mario Schiffer, Hans‐Ulrich Prokosch, Barbara Bärthlein, Andreas Beck, André Reis, Arif B. Ekici, Susanne Becker, Dinah Becker-Grosspitsch, Matthias Schmid, Birgit Hausknecht, Anke Weigel, Gerd Walz, Anna Köttgen, Ulla T. Schultheiß, Fruzsina Kotsis, Simone Meder, Erna Mitsch, Ursula Reinhard, Jürgen Floege, Turgay Saritas, Elke Schäeffner, Seema Baid‐Agrawal, Kerstin Theisen, Hermann Haller, Jan Menne, Martin Zeier, Claudia Sommerer, Johanna Theilinger, G Wolf, Martin Busch, Rainer Paul, Thomas Sitter, Christoph Wanner, Vera Krane, Antje Börner-Klein, Britta Bauer, Florian Kronenberg, Julia Raschenberger, Barbara Kollerits, Lukas Forer, Sebastian Schönherr, Hansi Weißensteiner, Peter J. Oefner, Wolfram Gronwald, Matthias Schmid, Jennifer Nadal
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.