Related Experiment Videos
Inflammation and advanced glycation end products in uremia: simple coexistence, potentiation or causal relationship?
S Schwedler1, R Schinzel, P Vaith
1Department of Medicine, Division of Nephrology, University of Würzburg, Würzburg, Germany. Pelleas@t-online.de
Insights
Cardiovascular disease in dialysis patients is linked to metabolic and inflammatory issues. Advanced glycation end products (AGEs) may drive C-reactive protein (CRP) production, contributing to atherosclerosis risk.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Biochemistry
Background:
- Dialysis patients exhibit high cardiovascular disease (CVD) rates due to multifactorial causes.
- Chronic uremia involves metabolic disturbances, oxidative stress, and immuno-inflammatory system activation.
- Accumulation of advanced glycation end products (AGEs) and advanced oxidation products (AOPPs) characterizes uremia, alongside acute phase response activation.
Purpose of the Study:
- To investigate the potential link between advanced glycation end products (AGEs) and C-reactive protein (CRP) production in uremic patients.
- To explore the role of AGEs in stimulating hepatic CRP production, potentially contributing to atherosclerosis.
Main Methods:
- Review of existing literature on cardiovascular disease in dialysis patients.
- Analysis of the role of AGEs, AOPPs, and acute phase reactants like CRP in uremia.
- Discussion of potential mechanisms involving AGEs, RAGE, and CRP production in hepatocytes and monocytes.
Main Results:
- High serum levels of AGEs, AOPPs, and acute phase reactants (CRP, fibrinogen, serum amyloid A) are observed in uremic patients.
- CRP predicts cardiovascular and overall mortality in hemodialysis patients.
- AGEs have been found in atherosclerotic lesions and can induce endothelial cell activation, suggesting a pathophysiological role.
Conclusions:
- AGEs accumulation in uremia may directly or indirectly stimulate hepatic CRP production.
- This AGEs-CRP axis could be a significant factor in the high incidence of atherosclerosis and mortality in dialysis patients.
- Further clinical studies are needed to confirm the predictive effects of AGEs on cardiovascular mortality in this population.
Abstract:
The causes for the high frequency of cardiovascular disease in dialysis patients are multifactorial in origin. Disturbances in the carbohydrate and lipid metabolism, the balance between oxidants and antioxidants and the immuno-inflammatory system are thought to play a role. Chronic uremia is characterized by the accumulation of advanced glycation end products (AGEs) and advanced oxidation products (AOPP) as well as activation of the acute phase response. High serum levels of these products and acute phase reactants such as C-reactive protein (CRP), fibrinogen and serum amyloid A can be found. CRP has been shown to predict cardiovascular and overall mortality in hemodialysis patients. Whether CRP is involved causally in atherosclerosis or merely represents a marker of disease is as yet unknown. Since CRP has been detected in colocalization with modified apolipoproteins or complement components in atherosclerotic lesions, a pathophysiological role seems very likely. AGEs as well have been detected in aortas of hemodialysis patients. Incubation of endothelial cells with AGEs induced expression of adhesion molecules with consecutive attraction of monocytes to the vessel wall. Thus far, clinical studies investigating the predictive effects of AGEs on cardiovascular mortality in hemodialysis patients are lacking. There is considerable debate about what factors turn on the acute phase response in this population. Proinflammatory effects of AGEs mediated through one receptor for AGEs, RAGE, have been described. We hypothesize that there may be a link between increased hepatic CRP production and the accumulation of AGEs in uremia. AGEs may stimulate CRP production in hepatocytes either directly or indirectly via interaction with monocytes.