Related Experiment Video
Updated: May 3, 2026
A Semi-Automated and Reproducible Biological-Based Method to Quantify Calcium Deposition In Vitro
Published on: June 2, 2022
Biomarkers of vascular calcification and mortality in patients with ESRD
Julia J Scialla1, W H Linda Kao, Ciprian Crainiceanu
1Department of Medicine, University of Miami, Miami, Florida;, †Department of Epidemiology,, §Department of Biostatistics, and, ‡Department of Medicine, Johns Hopkins University, Baltimore, Maryland;, ‖Department of Medicine, San Francisco General Hospital and University of California San Francisco, San Francisco, California;, ¶Department of Epidemiology, Emory University, Atlanta, Georgia;, *Nephrology Center of Maryland, Baltimore, Maryland, ††Hospital for Sick Children, University Health Network and University of Toronto, Toronto, Ontario, Canada.
Insights
Osteoprotegerin (OPG) and fetuin-A levels are linked to mortality in dialysis patients. Higher OPG and lower fetuin-A correlate with increased all-cause mortality, particularly in non-diabetic individuals.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Biomarkers
Background:
- Vascular calcification is a prevalent and fatal complication in dialysis patients.
- Key factors implicated include osteoprotegerin (OPG), osteopontin (OPN), bone morphogenic protein-7 (BMP-7), and fetuin-A.
Purpose of the Study:
- To investigate the association between OPG, OPN, BMP-7, and fetuin-A levels and mortality in incident dialysis patients.
- To explore the role of diabetes in these associations and assess the predictive accuracy of these biomarkers.
Main Methods:
- Blood samples from 602 incident dialysis patients were analyzed for OPG, OPN, BMP-7, and fetuin-A.
- Cox proportional hazards models were used to assess associations with all-cause and cardiovascular mortality, adjusting for covariates.
- Interactions with diabetes and predictive accuracy were evaluated.
Main Results:
- Elevated OPG and reduced fetuin-A levels were associated with increased all-cause mortality.
- OPG showed a stronger association with mortality in patients without diabetes.
- OPN and BMP-7 were not independently associated with mortality; biomarkers did not improve risk prediction.
Conclusions:
- OPG and fetuin-A may serve as risk factors for mortality in dialysis patients.
- These biomarkers, however, do not enhance the prediction of mortality risk.
- The interaction between OPG and diabetes warrants further investigation.
Background:
Vascular calcification is common among patients undergoing dialysis and is associated with mortality. Factors such as osteoprotegerin (OPG), osteopontin (OPN), bone morphogenic protein-7 (BMP-7), and fetuin-A are involved in vascular calcification.
Design, Setting, Participants, & Measurements:
OPG, OPN, BMP-7, and fetuin-A were measured in blood samples from 602 incident dialysis patients recruited from United States dialysis centers between 1995 and 1998 as part of the Choices for Healthy Outcomes In Caring for ESRD Study. Their association with all-cause and cardiovascular mortality were assessed using Cox proportional hazards models adjusted for demographic characteristics, comorbidity, serum phosphate, and calcium. An interaction with diabetes was tested because of its known association with vascular calcification. Predictive accuracy of selected biomarkers was explored by C-statistics in nested models with training and validation subcohorts.
Results:
Higher OPG and lower fetuin-A levels were associated with higher mortality over up to 13 years of follow-up (median, 3.4 years). The adjusted hazard ratios (HR) for highest versus lowest tertile were 1.49 (95% confidence interval [95% CI], 1.08 to 2.06) for OPG and 0.69 (95% CI, 0.52 to 0.92) for fetuin-A. In stratified models, the highest tertile of OPG was associated with higher mortality among patients without diabetes (HR, 2.42; 95% CI, 1.35 to 4.34), but not patients with diabetes (HR, 1.26; 95% CI, 0.82 to 1.93; P for interaction=0.001). In terms of cardiovascular mortality, higher fetuin-A was associated with lower risk (HR, 0.85 per 0.1 g/L: 95% CI, 0.75 to 0.96). In patients without diabetes, higher OPG was associated with greater risk (HR for highest versus lowest tertile, 2.91; 95% CI, 1.06 to 7.99), but not in patients with diabetes or overall. OPN and BMP-7 were not independently associated with outcomes overall. The addition of OPG and fetuin-A did not significantly improve predictive accuracy of mortality.
Conclusions:
OPG and fetuin-A may be risk factors for all-cause and cardiovascular mortality in patients undergoing dialysis, but do not improve risk prediction.
Related Concept Videos
01:25Imaging Studies for Cardiovascular System VI: Calcium -Scoring CT
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
01:24Chronic Kidney Disease II: Clinical Manifestations
01:20Blood Studies for Cardiovascular System I: Cardiac Biomarkers
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...
01:27Atherosclerosis II: Clinical Manifestations and Diagnostic Tests
01:20Imaging Studies for Cardiovascular System III: X-Ray
Definition and Purpose
An X-ray, or radiograph, is a non-invasive method that uses ionizing radiation to take images of internal structures. It is mainly used in cardiac imaging to examine the heart, lungs, and major blood vessels, aiming to identify abnormalities in the heart's size, shape, and position, such as heart failure, congenital defects, and vascular...