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Association between glomerular filtration rate and endothelial function in an elderly community cohort
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
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2012 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, no 1, 242-246 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Endothelial dysfunction is prevalent among individuals with chronic kidney disease. However, the association between glomerular filtration rate and endothelial function in the community is unclear and needs to be investigated in the general population.

METHODS: In the community-based Prospective Investigation of the Vasculature of Uppsala Seniors study (PIVUS, n = 952, mean age 70, women 49.3%), we investigated cross-sectional associations between estimated cystatin C-based glomerular filtration rate (eGFR), and 3 measures representing different aspects of endothelial function (endothelial-dependent vasodilation [EDV], endothelial independent vasodilatation [EIDV], and flow-mediated dilatation [FMD]). We also performed pre-specified sub-group analyses in participants with normal eGFR (>60 ml/min/1.73 m(2)).

RESULTS: In the whole cohort, 10 ml/min/1.73 m(2) higher eGFR was associated with 3% higher EDV (p = 0.001) and 2% higher EIDV (p = 0.007), adjusted for age and sex. The associations were attenuated and no longer statistically significant after adjusting for established cardiovascular risk factors. In participants with eGFR >60 ml/min/1.73 m(2), 10 ml higher eGFR was associated with 2% higher EDV (p = 0.04) after adjusting for sex and age. eGFR was not associated to FMD in any model or sub-sample.

CONCLUSION: This community-based study suggests that eGFR is associated with endothelial function also in persons with normal kidney function, but that this association is largely explained by confounding by established cardiovascular risk factors. Thus, our data do not support the notion of a direct causal interplay between renal and vascular function prior to the development of CKD.

Place, publisher, year, edition, pages
2012. Vol. 224, no 1, 242-246 p.
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-182339DOI: 10.1016/j.atherosclerosis.2012.07.008ISI: 000308078000038PubMedID: 22841608OAI: oai:DiVA.org:uu-182339DiVA: diva2:559481
Available from: 2012-10-09 Created: 2012-10-09 Last updated: 2017-12-07Bibliographically approved
In thesis
1. The Kidney in Different Stages of the Cardiovascular Continuum
Open this publication in new window or tab >>The Kidney in Different Stages of the Cardiovascular Continuum
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. The complex, interaction between the kidney and the cardiovascular system is incompletely understood, particularly at the early stages of the cardiovascular continuum.

The overall aim of this thesis was to clarify novel aspects of the interplay between the kidney and the cardiovascular system at different stages of the cardiovascular continuum; from risk factors such as insulin resistance, inflammation and oxidative stress, via sub-clinical cardiovascular damage such as endothelial dysfunction and left ventricular dysfunction, to overt cardiovascular death.

This thesis is based on two community-based cohorts of elderly, Uppsala Longitudinal Study of Adult Men (ULSAM) and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS).

The first study, show that higher insulin sensitivity, measured with euglycemic-hyperinsulinemic clamp technique was associated to improve estimated glomerular filtration rate (eGFR) in participants with normal fasting plasma glucose, normal glucose tolerance and normal eGFR. In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function during follow-up. In the second study, eGFR was inversely associated with different inflammatory markers (C-reactive protein, interleukin-6, serum amyloid A) and positively associated with a marker of oxidative stress (urinary F2-isoprostanes). In line with this, the urinary albumin/creatinine ratio was positively associated with these inflammatory markers, and negatively associated with oxidative stress.

In study three, higher eGFR was associated with better endothelial function as assessed by the invasive forearm model. Further, in study four, higher eGFR was significantly associated with higher left ventricular systolic function (ejection fraction). The 5th study of the thesis shows that higher urinary albumin excretion rate (UAER) and lower eGFR was independently associated with an increased risk for cardiovascular mortality. Analyses of global model fit, discrimination, calibration, and reclassification suggest that UAER and eGFR add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent cardiovascular disease.

Conclusion: this thesis show that the interaction between the kidney and the cardiovascular system plays an important role in the development of cardiovascular disease and that this interplay begins at an early asymptomatic stage of the disease process.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 72 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 946
Keyword
epidemiology, chronic kidney disease, cystatin C, glomerular filtration rate, albuminuria, euglycemic hyperinsulinemic clamp, insulin sensitivity, inflammation, oxidative stress, endothelial dysfunction and left ventricular dysfunction
National Category
Cardiac and Cardiovascular Systems Urology and Nephrology Gerontology, specializing in Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:uu:diva-209644 (URN)978-91-554-8792-8 (ISBN)
Public defence
2013-12-05, Universitetshuset, sal IX, Biskopsgatan 3, Uppsala, 09:00 (Swedish)
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Supervisors
Available from: 2013-11-14 Created: 2013-10-22 Last updated: 2014-01-23

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Nerpin, ElisabetRisérus, UlfHelmersson-Karlqvist, JohannaSundström, JohanJobs, ElisabethLarsson, AndersLind, LarsÄrnlöv, Johan

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