Journal article
Endothelial Microparticles and Systemic Complement Activation in Patients With Chronic Kidney Disease
Journal of the American Heart Association, Vol.7(14), p.7:e007818
2018
DOI: 10.1161/JAHA.117.007818
PMCID: PMC6064828
PMID: 30006493
Abstract
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 flowmediated 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.
Details
- Title: Subtitle
- Endothelial Microparticles and Systemic Complement Activation in Patients With Chronic Kidney Disease
- Creators
- Diana Jalal - Carver College of Medicine, University of IowaBrandon Renner - University of Colorado Anschutz [Aurora]Jennifer Laskowski - University of Colorado Anschutz [Aurora]Erik Stites - University of Colorado Anschutz [Aurora]James Cooper - University of Colorado Anschutz [Aurora]Karissa Valente - University of Colorado Anschutz [Aurora]Zhiying You - University of Colorado Anschutz [Aurora]Loni Perrenoud - University of Colorado Anschutz [Aurora]Moglie Le Quintrec - Centre Hospitalier Régional Universitaire [Montpellier]Ismaeel Muhamed - North Carolina State University [Raleigh]Uwe Christians - University of Colorado Anschutz [Aurora]Jelena Klawitter - University of Colorado Anschutz [Aurora]Margaret Lindorfer - University of Virginia [Charlottesville]Ronald Taylor - University of Virginia [Charlottesville]V. Michael Holers - University of Colorado Anschutz [Aurora]Joshua Thurman - University of Colorado Anschutz [Aurora]
- Resource Type
- Journal article
- Publication Details
- Journal of the American Heart Association, Vol.7(14), p.7:e007818
- DOI
- 10.1161/JAHA.117.007818
- PMID
- 30006493
- PMCID
- PMC6064828
- NLM abbreviation
- J Am Heart Assoc
- ISSN
- 2047-9980
- eISSN
- 2047-9980
- Publisher
- Wiley-Blackwell
- Language
- English
- Date published
- 2018
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984094581902771
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