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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Endothelial Microparticles and Systemic Complement Activation in Patients With Chronic Kidney Disease
Diana Jalal1, Brandon Renner2, Jennifer Laskowski2
1Division of Nephrology, Carver College of Medicine University of Iowa, Iowa City, IA diana-jalal@uiowa.edu.
Insights
Complement activation via endothelial microparticles is linked to chronic kidney disease (CKD) and endothelial dysfunction. Increased factor D in microparticles from CKD patients activates the alternative pathway, suggesting a role in vascular disease.
Area of Science:
- Nephrology
- Immunology
- Vascular Biology
Background:
- Endothelial microparticles are implicated in chronic kidney disease (CKD) and complement system activation.
- The study investigates the role of complement activation via endothelial microparticles in CKD patients.
Purpose of the Study:
- To determine if the complement pathway is activated in CKD patients through endothelial microparticles.
- To assess the correlation between complement activation and endothelial dysfunction in CKD.
Main Methods:
- Analysis of complement data in healthy subjects, CKD patients, and kidney transplant recipients.
- Evaluation of correlations between complement fragments, flow-mediated dilation, GFR, and albuminuria.
- Proteomic characterization of endothelial microparticles and in vitro pathway activation assays.
Main Results:
- Elevated complement fragment Ba in CKD and post-transplant CKD patients.
- Ba levels correlated with reduced flow-mediated dilation, lower GFR, and increased albuminuria.
- Increased Factor D in microparticles from CKD patients, which activated the alternative pathway in vitro.
Conclusions:
- The alternative complement pathway is activated in CKD, correlating with endothelial dysfunction and disease markers.
- Endothelial microparticles with elevated Factor D may contribute to CKD-associated vascular disease.
- Further research is needed to elucidate the pathological role of these microparticles.
Background:
Endothelial microparticles are associated with chronic kidney disease (CKD) and complement activation. We hypothesized that the complement pathway is activated in patients with CKD via endothelial microparticles and that complement activation correlates with endothelial dysfunction in CKD.
Methods And Results:
We analyzed complement data of 30 healthy subjects, 30 patients with stage III/IV CKD, and 30 renal transplant recipients with stage III/IV CKD, evaluating the potential correlation of complement fragments with brachial artery flow-mediated dilation, Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and urinary albumin/creatinine ratio. Endothelial microparticles were characterized via proteomic analysis and compared between study groups. Complement fragment Ba was significantly increased in CKD and post-kidney transplant CKD. Plasma Ba levels correlated significantly with lower brachial artery flow-mediated dilation, lower Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and higher urinary albumin/creatinine ratio. Factor D levels were significantly higher in the plasma microparticles of patients with CKD versus healthy controls. Plasma microparticles isolated from patients with CKD and containing factor D activated the alternative pathway in vitro.
Conclusion:
The alternative complement pathway is activated in CKD and correlates with endothelial dysfunction and markers of CKD. Future studies are needed to evaluate whether endothelial microparticles with increased factor D play a pathologic role in CKD-associated vascular disease.
Clinical Trial Registration:
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02230202.
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