Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort
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...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-10-01
|
| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-023-00291-8 |
| _version_ | 1827635243401609216 |
|---|---|
| author | Katharina Charlotte Reimer Jennifer Nadal Heike Meiselbach Matthias Schmid Ulla T. Schultheiss Fruzsina Kotsis Helena Stockmann Nele Friedrich Matthias Nauck Vera Krane Kai-Uwe Eckardt Markus P. Schneider Rafael Kramann Jürgen Floege Turgay Saritas on behalf of the GCKD study investigators |
| author_facet | Katharina Charlotte Reimer Jennifer Nadal Heike Meiselbach Matthias Schmid Ulla T. Schultheiss Fruzsina Kotsis Helena Stockmann Nele Friedrich Matthias Nauck Vera Krane Kai-Uwe Eckardt Markus P. Schneider Rafael Kramann Jürgen Floege Turgay Saritas on behalf of the GCKD study investigators |
| author_sort | Katharina Charlotte Reimer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T15:25:11Z |
| format | Article |
| id | doaj.art-3d09ae8388934e3592b7202dc7328f7f |
| institution | Directory Open Access Journal |
| issn | 2095-6231 |
| language | English |
| last_indexed | 2024-03-09T15:25:11Z |
| publishDate | 2023-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj.art-3d09ae8388934e3592b7202dc7328f7f2023-11-26T12:35:40ZengNature Publishing GroupBone Research2095-62312023-10-011111810.1038/s41413-023-00291-8Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohortKatharina Charlotte Reimer0Jennifer Nadal1Heike Meiselbach2Matthias Schmid3Ulla T. Schultheiss4Fruzsina Kotsis5Helena Stockmann6Nele Friedrich7Matthias Nauck8Vera Krane9Kai-Uwe Eckardt10Markus P. Schneider11Rafael Kramann12Jürgen Floege13Turgay Saritas14on behalf of the GCKD study investigatorsDepartment of Nephrology, Rheumatology, and Clinical Immunology, University Hospital RWTH AachenInstitute of Medical Biometry, Informatics and Epidemiology, University Hospital of BonnDepartment of Nephrology and Hypertension, University of Erlangen-NürnbergInstitute of Medical Biometry, Informatics and Epidemiology, University Hospital of BonnInstitute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of FreiburgInstitute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of FreiburgDepartment of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin BerlinInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine GreifswaldInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine GreifswaldDepartment of Medicine I, Division of Nephrology, University Hospital WürzburgDepartment of Nephrology and Hypertension, University of Erlangen-NürnbergDepartment of Nephrology and Hypertension, University of Erlangen-NürnbergDepartment of Nephrology, Rheumatology, and Clinical Immunology, University Hospital RWTH AachenDepartment of Nephrology, Rheumatology, and Clinical Immunology, University Hospital RWTH AachenDepartment of Nephrology, Rheumatology, and Clinical Immunology, University Hospital RWTH AachenAbstract 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.https://doi.org/10.1038/s41413-023-00291-8 |
| spellingShingle | Katharina Charlotte Reimer Jennifer Nadal Heike Meiselbach Matthias Schmid Ulla T. Schultheiss Fruzsina Kotsis Helena Stockmann Nele Friedrich Matthias Nauck Vera Krane Kai-Uwe Eckardt Markus P. Schneider Rafael Kramann Jürgen Floege Turgay Saritas on behalf of the GCKD study investigators Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort Bone Research |
| title | Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort |
| title_full | Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort |
| title_fullStr | Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort |
| title_full_unstemmed | Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort |
| title_short | Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort |
| title_sort | association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the german chronic kidney disease gckd cohort |
| url | https://doi.org/10.1038/s41413-023-00291-8 |
| work_keys_str_mv | AT katharinacharlottereimer associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT jennifernadal associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT heikemeiselbach associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT matthiasschmid associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT ullatschultheiss associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT fruzsinakotsis associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT helenastockmann associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT nelefriedrich associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT matthiasnauck associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT verakrane associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT kaiuweeckardt associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT markuspschneider associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT rafaelkramann associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT jurgenfloege associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT turgaysaritas associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort AT onbehalfofthegckdstudyinvestigators associationofmineralandbonebiomarkerswithadversecardiovascularoutcomesandmortalityinthegermanchronickidneydiseasegckdcohort |