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Original Article | Open Access

Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort

Katharina Charlotte Reimer1,2,3, Jennifer Nadal4, Heike Meiselbach5, Matthias Schmid4, Ulla T. Schultheiss6,7, Fruzsina Kotsis6,7, Helena Stockmann8,9, Nele Friedrich10,11, Matthias Nauck10,11, Vera Krane12, Kai-Uwe Eckardt5,8, Markus P. Schneider5, Rafael Kramann1,2, Jürgen Floege1, Turgay Saritas1,2 ( ), Mario Schiffer13, Hans-Ulrich Prokosch13, Barbara Bärthlein13, Andreas Beck13, André Reis13, Arif B. Ekici13, Susanne Becker13, Ulrike Alberth-Schmidt13, Anke Weigel13, Sabine Marschall13, Eugenia Schefler13, Gerd Walz14, Anna Köttgen14, Fruzsina Kotsis14, Simone Meder14, Erna Mitsch14, Ursula Reinhard14, Elke Schaeffner15, Seema Baid-Agrawal15, Kerstin Theisen15, Kai Schmidt-Ott16, Martin Zeier17, Claudia Sommerer17, Mehtap Aykac17, Gunter Wolf18, Rainer Paul18, Antje Börner-Klein19, Britta Bauer19, Julia Raschenberger20, Barbara Kollerits20, Lukas Forer20, Sebastian Schönherr20, Hansi Weissensteiner20, Peter Oefner21, Wolfram Gronwald21
Department of Nephrology, Rheumatology, and Clinical Immunology, University Hospital RWTH Aachen, Aachen, Germany
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
Institute for Cell and Tumor Biology, RWTH Aachen University, Aachen, Germany
Institute of Medical Biometry, Informatics and Epidemiology, University Hospital of Bonn, Bonn, Germany
Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany
Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
Department of Medicine Ⅳ – Nephrology and Primary Care, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany
Department of Nephrology, University Medical Center Regensburg, Regensburg, Germany
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine, Greifswald, Germany
Department of Medicine Ⅰ, Division of Nephrology, University Hospital Würzburg, Würzburg, Germany
University of Erlangen-Nürnberg, Erlangen, Germany
University of Freiburg, Freiburg, Germany
Charité University Medicine Berlin, Berlin, Germany
Hannover Medical School, Hannover, Germany
University of Heidelberg, Heidelberg, Germany
University of Jena, Jena, Germany
University of Würzburg, Würzburg, Germany
Medical University of Innsbruck, Institute of Genetic Epidemiology, Innsbruck, Austria
University of Regensburg, Institute of Functional Genomics, Regensburg, Germany
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Abstract

Mineral and bone disorder (MBD) in chronic kidney disease (CKD) is tightly linked to cardiovascular disease (CVD). In this study, we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated best with adverse cardiovascular (CV) outcomes and mortality. In 5 217 participants of the German CKD (GCKD) study enrolled with an estimated glomerular filtration rate (eGFR) between 30–60 mL·min−1 per 1.73 m2 or overt proteinuria, serum osteoprotegerin (OPG), C-terminal fibroblast growth factor-23 (FGF23), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), cross-linked C-telopeptide of type 1 collagen (CTX1), procollagen 1 intact N-terminal propeptide (P1NP), phosphate, calcium, and 25-OH vitamin D were measured at baseline. Participants with missing values among these parameters (n = 971) were excluded, leaving a total of 4 246 participants for analysis. During a median follow-up of 6.5 years, 387 non-CV deaths, 173 CV deaths, 645 nonfatal major adverse CV events (MACEs) and 368 hospitalizations for congestive heart failure (CHF) were observed. OPG and FGF23 were associated with all outcomes, with the highest hazard ratios (HRs) for OPG. In the final Cox regression model, adjusted for CV risk factors, including kidney function and all other investigated biomarkers, each standard deviation increase in OPG was associated with non-CV death (HR 1.76, 95% CI: 1.35–2.30), CV death (HR 2.18, 95% CI: 1.50–3.16), MACE (HR 1.38, 95% CI: 1.12–1.71) and hospitalization for CHF (HR 2.05, 95% CI: 1.56–2.69). Out of the nine biomarkers examined, stratification based on serum OPG best identified the CKD patients who were at the highest risk for any adverse CV outcome and mortality.

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Bone Research
Volume 11,
December 2023
Article number: 52
DOI: 10.1038/s41413-023-00291-8
Cite this article:
Reimer KC, Nadal J, Meiselbach H, et al. Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort. Bone Research, 2023, 11: 52. https://doi.org/10.1038/s41413-023-00291-8

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Received: 28 March 2023
Accepted: 07 September 2023
Published: 20 October 2023
© The Author(s) 2023

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