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Novel Biomarkers Detected by Proteomics Predict Death and Cardiovascular Events in Hemodialysis Patients
Ping-Hsun Wu1,2,3, Rie Io Glerup4, My Hanna Sofia Svensson5
1Department of Medical Sciences, Uppsala University, 75236 Uppsala, Sweden.
Insights
Novel protein biomarkers, including Interleukin-8 (IL-8), T-cell immunoglobulin and mucin domain 1 (TIM-1), and C-C motif chemokine 20 (CCL20), predict mortality and cardiovascular events in hemodialysis patients. Stem cell factor (SCF) and Galanin peptides (GAL) show protective associations.
Area of Science:
- Nephrology
- Cardiology
- Biomarker Discovery
Background:
- End-stage kidney disease (ESKD) significantly elevates mortality and cardiovascular (CV) disease risk.
- Hemodialysis (HD) patients face complex challenges in predicting adverse CV outcomes.
- Identifying novel biomarkers is critical for risk stratification in this population.
Purpose of the Study:
- To investigate the association between 92 targeted proteins and mortality and CV events in HD patients.
- To identify novel protein biomarkers for predicting all-cause death, CV death, and composite vascular events (CVEs).
Main Methods:
- Prospective study of 331 HD patients followed for 5 years.
- Serum protein analysis using Proseek Multiplex Cardiovascular I panel (proximity extension assay technology).
- Cox-regression analyses to evaluate associations between proteins and clinical outcomes.
Main Results:
- Twenty proteins associated with all-cause death, 7 with CV death, and 17 with CVEs were identified.
- Interleukin-8 (IL-8), TIM-1, and CCL20 independently predicted increased risk of death and CVEs.
- Stem cell factor (SCF) and Galanin peptides (GAL) were associated with decreased risk of all-cause and CV death.
Conclusions:
- IL-8, TIM-1, and CCL20 are significant predictors of mortality and CV outcomes in HD patients.
- SCF and GAL represent novel protective biomarkers in this high-risk cohort.
- Further research into the biological role of SCF in HD patients is warranted.
Abstract:
End-stage kidney disease increases mortality and the risk of cardiovascular (CV) disease. It is crucial to explore novel biomarkers to predict CV disease in the complex setting of patients receiving hemodialysis (HD). This study investigated the association between 92 targeted proteins with all-cause death, CV death, and composite vascular events (CVEs) in HD patients. From December 2010 to March 2011, 331 HD patients were included and followed prospectively for 5 years. Serum was analyzed for 92 CV-related proteins using Proseek Multiplex Cardiovascular I panel, a high-sensitivity assay based on proximity extension assay (PEA) technology. The association between biomarkers and all-cause death, CV death, and CVEs was evaluated using Cox-regression analyses. Of the PEA-based proteins, we identified 20 proteins associated with risk of all-cause death, 7 proteins associated with risk of CV death, and 17 proteins associated with risk of CVEs, independent of established risk factors. Interleukin-8 (IL-8), T-cell immunoglobulin and mucin domain 1 (TIM-1), and C-C motif chemokine 20 (CCL20) were associated with increased risk of all-cause death, CV death, and CVE in multivariable-adjusted models. Stem cell factor (SCF) and Galanin peptides (GAL) were associated with both decreased risk of all-cause death and CV death. In conclusion, IL-8, TIM-1, and CCL20 predicted death and CV outcomes in HD patients. Novel findings were that SCF and GAL were associated with a lower risk of all-cause death and CV death. The SCF warrants further study with regard to its possible biological effect in HD patients.
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