臺灣博碩士論文加值系統

Background: Patients on maintenance hemodialysis due to end-stage renal disease (ESRD) have an increased risk for cardiovascular diseases (CVDs). Inflammation and endothelial dysfunction are involved in atherosclerosis and CVDs. Age-related immune changes (including lymphocytes and monocytes) are more severe in ESRD. However, the contribution of immunological aging to CVD in ESRD patients is not clear.
Methods: In this cross-sectional study, blood samples from 199 ESRD patients on maintenance hemodialysis and 57 healthy individuals were analyzed. By multicolor flow cytometry, lymphocytes were separated into subpopulations that include naïve, central memory, effector memory and terminally differentiated CD4 and CD8 T cells. Monocytes were separated into classical, intermediate and non-classical monocytes. In hemodialysis patients, CVDs including stroke, peripheral artery occlusive disease (PAOD) and coronary artery disease (CAD) were ascertained based on hospital medical records.
Results: Compared to healthy individuals, hemodialysis patients showed lower level of naïve CD4 and CD8 T cells, but higher level of effector memory and terminally differentiated cells. Differentiation in monocytes also differed between hemodialysis and healthy individuals, where there was an increase in percentage of intermediate (CD14++CD16+) and non-classical (CD14+CD++) monocytes, and a decrease in classical monocytes (CD14++CD16-) in hemodialysis patients. Levels of naïve CD8+ T cell and terminally differentiated T cell were significantly correlated with age in hemodialysis patients. In a multiple logistic regression model, higher percentage of CD8+ terminally differentiated T cell was significantly associated with increased risk of CVDs (adjusted odds ratio (AOR) = 1.02, and 95% confidence interval (CI) 1.00 – 1.04, P-value=0.04) after adjusting for age, gender, cholesterol, triglyceride, diabetes, C-reactive protein (CRP) and hemoglobin (Hb).
Conclusion: This study demonstrated how the immune system of ESRD patients on hemodialysis differs from healthy individuals. Age-related immune changes, especially CD8+ terminally differentiated T cell, are associated with concurrent CVD in ESRD.

Table of Contents i
Acknowledgements iii
Abstract iv
Abbreviations vi
1. Introduction 1
1.1 Background 1
1.1.1 Epidemiology of end-stage renal disease (ESRD) 1
1.1.2 Cardiovascular diseases in ESRD patients on hemodialysis and risk factors. 2
1.1.3 Immune mechanism in atherosclerosis and CVDs 5
1.1.4 Immunosenescences (immune aging) in ESRD patients: 6
1.2 Motivation and significance 8
1.3 Conceptual framework 8
1.4 Research objectives 9
2. Methods 10
2.1 The subjects 10
2.2 Inclusion and Exclusion Criteria 10
2.3 Procedure and Data collection 10
2.4 Differentiation process of T cells and Monocytes 11
2.5 Immune cellular markers 12
2.6 Outcome variable 12
2.7 Potential confounders 13
2.8 Statistical analysis 13
3. Results 14
3.1 Differences in immune cellular markers between hemodialysis patients and healthy individuals 14
3.2 Associations between immune cellular markers and age, comorbidities in hemodialysis patient. 14
3.3 Immune cellular markers and risk of CVD in hemodialysis patients 15
4. Discussion 16
4.1 Strengths and Limitation 18
Conclusions 19
References 20
Tables 23
Figures 27
Appendix 31

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