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Endothelial function, CRP and oxidative stress in chronic kidney disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Njuemedicin)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Njurmedicin)ORCID iD: 0000-0001-6710-6422
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Njurmedicin)
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2005 (English)In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 18, no 6, p. 721-726Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Chronic kidney disease (CKD) is associated with increased morbidity and mortality in cardiovascular disease (CVD). Apart from traditional risk factors, chronic inflammation, oxidative stress, malnutrition and endothelial dysfunction are important in CVD development in renal patients. Our aim was to investigate the relationship between high sensitivity C-reactive protein (CRP), endothelium dependent vasodilation (EDV) and oxidative stress markers in patients with CKD K/DOQI stage 3-5.

METHODS: Measurements of CRP, conjugated dienes (CD), lipid hydroperoxide (LOOH), oxidized low density lipoprotein,glutathione and albumin were performed in 44 consecutive patients with CKD stage 3-5. EDV was measured by methacholine infusion in the brachial artery and venous occlusion plethysmography.

RESULTS: Patients with high CRP had significantly lower glomerular filtration rates and albumin, but increased LOOH and CD. In multiple regression analysis, only LOOH and CD remained significant. Patients with poor EDV had increased urea and lower glutathione (GSH). In multiple regression analysis, GSH and urea were independently related to EDV. No correlation was found between CRP and endothelial function.

CONCLUSION: CRP was related to lipid peroxidation, while endothelial function was related to intracellular oxidative stress in patients with CKD. CRP and EDV were unrelated to each other. Therefore, CRP and endothelial function could provide complementary prognostic information regarding future cardiovascular disorders in renal patients.

Place, publisher, year, edition, pages
2005. Vol. 18, no 6, p. 721-726
Keywords [en]
Biological Markers/blood, Brachial Artery/physiopathology, C-Reactive Protein/*metabolism, Comparative Study, Disease Progression, Endothelium; Vascular/*physiopathology, Enzyme-Linked Immunosorbent Assay, Female, Glomerular Filtration Rate/physiology, Humans, Kidney Failure; Chronic/*blood/physiopathology, Lipid Peroxides/blood, Lipoproteins; LDL/blood, Male, Middle Aged, Oxidative Stress/*physiology, Plethysmography, Prognosis, Research Support; Non-U.S. Gov't, Vasodilation/*physiology
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-94636PubMedID: 16358230OAI: oai:DiVA.org:uu-94636DiVA, id: diva2:168548
Available from: 2006-06-01 Created: 2006-06-01 Last updated: 2017-12-14
In thesis
1. Renal Dysfunction and Cardiovascular Disease
Open this publication in new window or tab >>Renal Dysfunction and Cardiovascular Disease
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Kidney dysfunction increases cardiovascular disease (CVD) risk. The mechanisms for the risk increase seem to involve a combination of traditional and non-traditional CVD risk factors.

We studied renal dysfunction as CVD and mortality risk factor in middle-aged men free from diabetes and CVD. The risk for myocardial infarction (MI) and CVD mortality was increased by ~40% in the 16.5% of men with worse renal function, independent of other CVD risk factors.

Renal transplant dysfunction as CVD and mortality risk factor was also studied. Renal transplant dysfunction was a risk factor for mortality and for combined CVD endpoint. The risk by renal transplant dysfunction was independent of traditional CVD risk factors as well as transplantation-specific risk factors. Only moderate increase in serum creatinine resulted in mortality and CVD risk comparable to diabetes, older age and higher low density lipoprotein levels.

In haemodialysis patients, the effects of a dialysis session on non-traditional CVD risk factors were studied. A HD session reduced asymmetric dimethylarginine (ADMA) and homocysteine levels, as well as augmentation index (AIx). The change in AIx was related to ADMA plasma level change.

In patients with stage 3-5 chronic kidney disease (CKD), endothelium dependent vasodilation (EDV) was studied together with markers of oxidative stress and C-reactive protein (CRP). CRP was related to lipid peroxidation, while EDV was related to intracellular antioxidative capacity measured by reduced glutathione levels.

These studies demonstrate that mild to moderate renal dysfunction is independently associated with increased CVD risk in apparently healthy people, as well as in renal transplant recipients. The mechanisms by which renal dysfunction increases CVD risk are yet to be elucidated. We suggest that arterial stiffness could be reduced in haemodialysis patients by increasing nitric oxide bioavailability. In stage 3-5 CKD patients, improving intracellular antioxidative capacity may result in endothelial function improvement.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. p. 75
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 158
Keywords
Internal medicine, renal dysfunktion, cardiovascular disease, risk factor, mortality, endothelial dysfunction, arterial stiffness, oxidative stress, inflammation, renal transplantation, haemodialysis, general population, Invärtesmedicin
Identifiers
urn:nbn:se:uu:diva-6941 (URN)91-554-6594-3 (ISBN)
Public defence
2006-09-15, Enghoffsalen, Akademiska Sjukhuset, ing 50, Uppsala, 09:15
Opponent
Supervisors
Available from: 2006-06-01 Created: 2006-06-01 Last updated: 2013-06-13Bibliographically approved

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Annuk, MargusSoveri, IngaLind, LarsFellström, Bengt

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