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The AGES-Reykjavik Study suggests that change in kidney measures is associated with subclinical brain pathology in older community-dwelling persons.

https://arctichealth.org/en/permalink/ahliterature292670
Source
Kidney Int. 2018 Jun 27; :
Publication Type
Journal Article
Date
Jun-27-2018
Author
Sanaz Sedaghat
Jie Ding
Gudny Eiriksdottir
Mark A van Buchem
Sigurdur Sigurdsson
M Arfan Ikram
Osorio Meirelles
Vilmundur Gudnason
Andrew S Levey
Lenore J Launer
Author Affiliation
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Source
Kidney Int. 2018 Jun 27; :
Date
Jun-27-2018
Language
English
Publication Type
Journal Article
Abstract
Decreased glomerular filtration rate (GFR) and albuminuria may be accompanied by brain pathology. Here we investigated whether changes in these kidney measures are linked to development of new MRI-detected infarcts and microbleeds, and progression of white matter hyperintensity volume. The study included 2671 participants from the population-based AGES-Reykjavik Study (mean age 75, 58.7% women). GFR was estimated from serum creatinine, and albuminuria was assessed by urinary albumin-to-creatinine ratio. Brain MRI was acquired at baseline (2002-2006) and 5 years later (2007-2011). New MRI-detected infarcts and microbleeds were counted on the follow-up scans. White matter hyperintensity progression was estimated as percent change in white matter hyperintensity volumes between the two exams. Participants with a large eGFR decline (over 3 ml/min per 1.73m2 per year) had more incident subcortical infarcts (odds ratio 1.53; 95% confidence interval 1.05, 2.22), and more marked progression of white matter hyperintensity volume (difference: 8%; 95% confidence interval: 4%, 12%), compared to participants without a large decline. Participants with incident albuminuria (over 30 mg/g) had 21% more white matter hyperintensity volume progression (95% confidence interval: 14%, 29%) and 1.86 higher odds of developing new deep microbleeds (95% confidence interval 1.16, 2.98), compared to participants without incident albuminuria. The findings were independent of cardiovascular risk factors. Changes in kidney measures were not associated with occurrence of cortical infarcts. Thus, larger changes in eGFR and albuminuria are associated with increased risk for developing manifestations of cerebral small vessel disease. Individuals with larger changes in these kidney measures should be considered as a high risk population for accelerated brain pathology.
PubMed ID
29960746 View in PubMed
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The AGES-Reykjavik Study suggests that change in kidney measures is associated with subclinical brain pathology in older community-dwelling persons.

https://arctichealth.org/en/permalink/ahliterature300494
Source
Kidney Int. 2018 09; 94(3):608-615
Publication Type
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Date
09-2018
Author
Sanaz Sedaghat
Jie Ding
Gudny Eiriksdottir
Mark A van Buchem
Sigurdur Sigurdsson
M Arfan Ikram
Osorio Meirelles
Vilmundur Gudnason
Andrew S Levey
Lenore J Launer
Author Affiliation
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Source
Kidney Int. 2018 09; 94(3):608-615
Date
09-2018
Language
English
Publication Type
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Keywords
Aged
Albuminuria - physiopathology - urine
Cerebral Small Vessel Diseases - diagnosis - epidemiology
Creatinine - urine
Disease Progression
Female
Follow-Up Studies
Glomerular Filtration Rate - physiology
Humans
Incidence
Independent living
Kidney - physiopathology
Magnetic Resonance Imaging
Male
Prospective Studies
Renal Insufficiency, Chronic - physiopathology - urine
Risk factors
Serum Albumin
White Matter - diagnostic imaging - pathology
Abstract
Decreased glomerular filtration rate (GFR) and albuminuria may be accompanied by brain pathology. Here we investigated whether changes in these kidney measures are linked to development of new MRI-detected infarcts and microbleeds, and progression of white matter hyperintensity volume. The study included 2671 participants from the population-based AGES-Reykjavik Study (mean age 75, 58.7% women). GFR was estimated from serum creatinine, and albuminuria was assessed by urinary albumin-to-creatinine ratio. Brain MRI was acquired at baseline (2002-2006) and 5 years later (2007-2011). New MRI-detected infarcts and microbleeds were counted on the follow-up scans. White matter hyperintensity progression was estimated as percent change in white matter hyperintensity volumes between the two exams. Participants with a large eGFR decline (over 3 ml/min/1.73m2 per year) had more incident subcortical infarcts (odds ratio 1.53; 95% confidence interval 1.05, 2.22), and more marked progression of white matter hyperintensity volume (difference: 8%; 95% confidence interval: 4%, 12%), compared to participants without a large decline. Participants with incident albuminuria (over 30 mg/g) had 21% more white matter hyperintensity volume progression (95% confidence interval: 14%, 29%) and 1.86 higher odds of developing new deep microbleeds (95% confidence interval 1.16, 2.98), compared to participants without incident albuminuria. The findings were independent of cardiovascular risk factors. Changes in kidney measures were not associated with occurrence of cortical infarcts. Thus, larger changes in eGFR and albuminuria are associated with increased risk for developing manifestations of cerebral small vessel disease. Individuals with larger changes in these kidney measures should be considered as a high risk population for accelerated brain pathology.
PubMed ID
29960746 View in PubMed
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Aortic stiffness and change in glomerular filtration rate and albuminuria in older people.

https://arctichealth.org/en/permalink/ahliterature272828
Source
Nephrol Dial Transplant. 2016 Mar 28;
Publication Type
Article
Date
Mar-28-2016
Author
Naya Huang
Meredith C Foster
Gary F Mitchell
Margret B Andresdottir
Gudny Eiriksdottir
Hrefna Gudmundsdottir
Tamara B Harris
Lenore J Launer
Runolfur Palsson
Vilmundur Gudnason
Andrew S Levey
Lesley A Inker
Source
Nephrol Dial Transplant. 2016 Mar 28;
Date
Mar-28-2016
Language
English
Publication Type
Article
Abstract
Aortic stiffness increases with age and increases pulsatile stress in the microcirculation. Abnormalities in kidney microvascular structure and function may contribute to development or progression of chronic kidney disease in older people.
We performed a longitudinal analysis of 629 community-dwelling elderly Icelandic adults from the Age, Gene/Environment Susceptibility-Reykjavik Study with two visits over a mean follow-up of 5.3 years. We evaluated the associations of carotid-femoral pulse wave velocity (CFPWV), carotid pulse pressure (CPP) and augmentation index (AI), with the change in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) assessed as annual change and dichotomized as large changes. Models were adjusted for age, sex, height, heart rate, traditional cardiovascular disease risk factors and baseline kidney measures.
When eGFR was analyzed as a continuous variable, higher baseline CFPWV and CPP, but not AI, were significantly associated with a larger annual decline in eGFR in models adjusted for age, sex, height, heart rate and baseline eGFR, but not after additional adjustment for the mean arterial pressure. When eGFR was analyzed as a categorical variable, higher CFPWV was significantly associated with a decrease in eGFR of =3 mL/min/1.73 m(2)/year [odds ratio (OR) 1.53, 95% confidence interval (CI) 1.11-2.13] and higher AI was associated with 30% eGFR decline during follow-up (OR 1.44 and 95% CI 1.03-2.00) in fully adjusted models. None of the tonometry measures was associated with change in UACR.
Abnormalities in vascular health may play a role in large declines in eGFR beyond the traditional cardiovascular disease risks in this older Icelandic cohort.
PubMed ID
27190377 View in PubMed
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Aortic Stiffness and Kidney Disease in an Elderly Population.

https://arctichealth.org/en/permalink/ahliterature263666
Source
Am J Nephrol. 2015 Jun 6;41(4-5):320-328
Publication Type
Article
Date
Jun-6-2015
Author
Katherine H Michener
Gary F Mitchell
Farzad Noubary
Naya Huang
Tamara Harris
Margret B Andresdottir
Runolfur Palsson
Vilmundur Gudnason
Andrew S Levey
Source
Am J Nephrol. 2015 Jun 6;41(4-5):320-328
Date
Jun-6-2015
Language
English
Publication Type
Article
Abstract
The causes of chronic kidney disease (CKD) in older people are not well understood. Aortic stiffness increases with age and results in the transmission of increased pulsatility into the kidney microvasculature, potentially contributing to CKD in older populations.
We utilized data from the Age, Gene/Environment, Susceptibility-Reykjavik Study, a community-based prospective cohort study of cardiovascular disease (CVD) in Iceland. The relationship of carotid pulse pressure (CPP) and carotid-femoral pulse wave velocity (CFPWV) with estimated glomerular filtration rate (eGFR) based on creatinine and cystatin C and urine albumin-creatinine ratio (ACR) was assessed using linear regression, adjusting for demographics and CVD risk factors.
940 participants (mean (SD) age 75.8 (4.7) years, mean (SD) CFPWV 12.9 (4.2) m/s, mean (SD) CPP 69 (21) mm Hg, mean (SD) eGFR 68 (16) ml/min/1.73 m(2), and median (IQR) ACR 3 (2-6) mg/g) were included in this study. At CPP greater than 85 mm Hg, a higher CPP was associated with a lower eGFR in unadjusted analyses but not after adjustment. CPP was significantly associated with a higher ACR in fully adjusted models (ß (95% CI) = 0.14 (0.03, 0.24) ln mg/g per SD). Higher CFPWV was associated with lower eGFR and higher ACR in unadjusted analyses but not after adjustment.
Greater aortic stiffness may be associated with modestly higher levels of albuminuria in the elderly. The association between aortic stiffness and lower eGFR may be confounded by age and CVD risk factors. © 2015 S. Karger AG, Basel.
PubMed ID
26067356 View in PubMed
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Associations between arterial stiffness, depressive symptoms and cerebral small vessel disease: cross-sectional findings from the AGES-Reykjavik Study.

https://arctichealth.org/en/permalink/ahliterature267325
Source
J Psychiatry Neurosci. 2015 Oct 20;41(1):140334
Publication Type
Article
Date
Oct-20-2015
Author
Thomas T van Sloten
Gary F Mitchell
Sigurdur Sigurdsson
Mark A van Buchem
Palmi V Jonsson
Melissa E Garcia
Tamara B Harris
Ronald M A Henry
Andrew S Levey
Coen D A Stehouwer
Vilmundur Gudnason
Lenore J Launer
Source
J Psychiatry Neurosci. 2015 Oct 20;41(1):140334
Date
Oct-20-2015
Language
English
Publication Type
Article
Abstract
Arterial stiffness may contribute to depression via cerebral microvascular damage, but evidence for this is scarce. We therefore investigated whether arterial stiffness is associated with depressive symptoms and whether cerebral small vessel disease contributes to this association.
This cross-sectional study included a subset of participants from the AGES-Reykjavik study second examination round, which was conducted from 2007 to 2011. Arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]), depressive symptoms (15-item geriatric depression scale [GDS-15]) and cerebral small vessel disease (MRI) were determined. Manifestations of cerebral small vessel disease included higher white matter hyperintensity volume, subcortical infarcts, cerebral microbleeds, Virchow-Robin spaces and lower total brain parenchyma volume.
We included 2058 participants (mean age 79.6 yr; 59.0% women) in our analyses. Higher CFPWV was associated with a higher GDS-15 score, after adjustment for potential confounders (ß 0.096, 95% confidence interval [CI] 0.005-0.187). Additional adjustment for white matter hyperintensity volume or subcortical infarcts attenuated the association between CFPWV and the GDS-15 score, which became nonsignificant (p > 0.05). Formal mediation tests showed that the attenuating effects of white matter hyperintensity volume and subcortical infarcts were statistically significant. Virchow-Robin spaces, cerebral microbleeds and cerebral atrophy did not explain the association between CFPWV and depressive symptoms.
Our study was limited by its cross-sectional design, which precludes any conclusions about causal mediation. Depressive symptoms were assessed by a self-report questionnaire.
Greater arterial stiffness is associated with more depressive symptoms; this association is partly accounted for by white matter hyperintensity volume and subcortical infarcts. This study supports the hypothesis that arterial stiffness leads to depression in part via cerebral small vessel disease.
PubMed ID
26505140 View in PubMed
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Comparing GFR Estimating Equations Using Cystatin C and Creatinine in Elderly Individuals.

https://arctichealth.org/en/permalink/ahliterature258516
Source
J Am Soc Nephrol. 2014 Dec 19;
Publication Type
Article
Date
Dec-19-2014
Author
Li Fan
Andrew S Levey
Vilmundur Gudnason
Gudny Eiriksdottir
Margret B Andresdottir
Hrefna Gudmundsdottir
Olafur S Indridason
Runolfur Palsson
Gary Mitchell
Lesley A Inker
Source
J Am Soc Nephrol. 2014 Dec 19;
Date
Dec-19-2014
Language
English
Publication Type
Article
Abstract
Current guidelines recommend reporting eGFR using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations unless other equations are more accurate, and recommend the combination of creatinine and cystatin C (eGFRcr-cys) as more accurate than either eGFRcr or eGFRcys alone. However, preferred equations and filtration markers in elderly individuals are debated. In 805 adults enrolled in the community-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we measured GFR (mGFR) using plasma clearance of iohexol, standardized creatinine and cystatin C, and eGFR using the CKD-EPI, Japanese, Berlin Initiative Study (BIS), and Caucasian and Asian pediatric and adult subjects (CAPA) equations. We evaluated equation performance using bias, precision, and two measures of accuracy. We first compared the Japanese, BIS, and CAPA equations with the CKD-EPI equations to determine the preferred equations, and then compared eGFRcr and eGFRcys with eGFRcr-cys using the preferred equations. Mean (SD) age was 80.3 (4.0) years. Median (25th, 75th) mGFR was 64 (52, 73) ml/min per 1.73 m(2), and the prevalence of decreased GFR was 39% (95% confidence interval, 35.8 to 42.5). Among 24 comparisons with the other equations, CKD-EPI equations performed better in 9, similar in 13, and worse in 2. Using the CKD-EPI equations, eGFRcr-cys performed better than eGFRcr in four metrics, better than eGFRcys in two metrics, and similar to eGFRcys in two metrics. In conclusion, neither the Japanese, BIS, nor CAPA equations were superior to the CKD-EPI equations in this cohort of community-dwelling elderly individuals. Using the CKD-EPI equations, eGFRcr-cys performed better than eGFRcr or eGFRcys.
PubMed ID
25527647 View in PubMed
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Comparison of glomerular filtration rate estimating equations derived from creatinine and cystatin C: validation in the Age, Gene/Environment Susceptibility-Reykjavik elderly cohort.

https://arctichealth.org/en/permalink/ahliterature286484
Source
Nephrol Dial Transplant. 2017 Oct 05;
Publication Type
Article
Date
Oct-05-2017
Author
Jonas Björk
Anders Grubb
Vilmundur Gudnason
Olafur S Indridason
Andrew S Levey
Runolfur Palsson
Ulf Nyman
Source
Nephrol Dial Transplant. 2017 Oct 05;
Date
Oct-05-2017
Language
English
Publication Type
Article
Abstract
Validation studies comparing glomerular filtration rate (GFR) equations based on standardized creatinine and cystatin C assays in the elderly are needed. The Icelandic Age, Gene/Environment Susceptibility-Kidney cohort was used to compare two pairs of recently developed GFR equations, the revised Lund-Malmö creatinine equation (LMRCr) and the arithmetic mean of the LMRCr and Caucasian, Asian, Paediatric and Adult cystatin C equations (MEANLMR+CAPA), as well as the Full Age Spectrum creatinine equation (FASCr) and its combination with cystatin C (FASCr+Cys), with the corresponding pair of Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPICr and CKD-EPICr+Cys).
A total of 805 individuals, 74-93?years of age, underwent measurement of GFR (mGFR) using plasma clearance of iohexol. Four metrics were used to compare the performance of the GFR equations: bias, precision, accuracy [including the percentage of participants with estimated GFR (eGFR) within 30% of mGFR (P30)] and the ability to detect mGFR?90%. LMRCr and FASCr yielded significantly higher precision and P30 than CKD-EPICr, while bias was significantly worse. LMRCr, FASCr and CKD-EPICr showed similar ability to detect mGFR?
PubMed ID
29040701 View in PubMed
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Lifetime Risk of Stage 3-5 CKD in a Community-Based Sample in Iceland.

https://arctichealth.org/en/permalink/ahliterature265520
Source
Clin J Am Soc Nephrol. 2015 Aug 18;
Publication Type
Article
Date
Aug-18-2015
Author
Lesley A Inker
Hocine Tighiouart
Thor Aspelund
Vilmundur Gudnason
Tamara Harris
Olafur S Indridason
Runolfur Palsson
Shani Shastri
Andrew S Levey
Mark J Sarnak
Source
Clin J Am Soc Nephrol. 2015 Aug 18;
Date
Aug-18-2015
Language
English
Publication Type
Article
Abstract
Lifetime risk estimates of CKD can be used effectively in public education campaigns. This study sought to estimate lifetime risk of incident CKD stage 3 and higher in Iceland for people without CKD by the age of 45 years.
This was a prospective cohort study with longitudinal creatinine measurements of residents in Reykjavik, Iceland, from 1967 to 2005. CKD was ascertained by two consecutive eGFR measurements
PubMed ID
26286924 View in PubMed
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Mediation Analysis of Aortic Stiffness and Renal Microvascular Function.

https://arctichealth.org/en/permalink/ahliterature257071
Source
J Am Soc Nephrol. 2014 Oct 7;
Publication Type
Article
Date
Oct-7-2014
Author
Todd Woodard
Sigurdur Sigurdsson
John D Gotal
Alyssa A Torjesen
Lesley A Inker
Thor Aspelund
Gudny Eiriksdottir
Vilmundur Gudnason
Tamara B Harris
Lenore J Launer
Andrew S Levey
Gary F Mitchell
Author Affiliation
Cardiovascular Engineering Inc., Norwood, Massachusetts;
Source
J Am Soc Nephrol. 2014 Oct 7;
Date
Oct-7-2014
Language
English
Publication Type
Article
Abstract
Aortic stiffening, assessed by carotid-femoral pulse wave velocity, is associated with CKD. Transmission of excessive flow pulsatility into the low-impedance renal microvasculature may mediate this association. However, direct analyses of macrovascular-microvascular relations in the kidney are limited. Using arterial tonometry, iohexol clearance, and magnetic resonance imaging, we related arterial stiffness, GFR, urinary albumin excretion, and potential mediators, including renal artery pulsatility index, renal vascular resistance, and arterial volume in the cortex, in 367 older adults (ages 72-92 years) participating in the Age, Gene/Environment Susceptibility-Reykjavik Study. In a model adjusted for age, sex, heart rate, and body size, aortic stiffness was related to GFR (Slope of regression B=-2.28?0.85 ml/min per SD, P=0.008) but not urine albumin (P=0.09). After accounting for pulsatility index, the relation between aortic stiffness and GFR was no longer significant (P=0.10). Mediation analysis showed that 34% of the relation between aortic stiffness and GFR was mediated by pulsatility index (95% confidence interval of indirect effect, -1.35 to -0.29). An additional 20% or 36% of the relation was mediated by lower arterial volume in the cortex or higher renal vascular resistance, respectively, when offered as mediators downstream from higher pulsatility index (95% confidence interval of indirect effect including arterial volume in the cortex, -2.22 to -0.40; 95% confidence interval of indirect effect including renal vascular resistance, -2.51 to -0.76). These analyses provide the first evidence that aortic stiffness may contribute to lower GFR by transferring excessive flow pulsatility into the susceptible renal microvasculature, leading to dynamic constriction or vessel loss.
PubMed ID
25294231 View in PubMed
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Midlife Blood Pressure and Late-Life GFR and Albuminuria: An Elderly General Population Cohort.

https://arctichealth.org/en/permalink/ahliterature262913
Source
Am J Kidney Dis. 2015 May 15;
Publication Type
Article
Date
May-15-2015
Author
Lesley A Inker
Aghogho Okparavero
Hocine Tighiouart
Thor Aspelund
Margret B Andresdottir
Gudny Eiriksdottir
Tamara Harris
Lenore Launer
Hjalmfridur Nikulasdottir
Johanna Eyrun Sverrisdottir
Hrefna Gudmundsdottir
Farzad Noubary
Gary Mitchell
Runolfur Palsson
Olafur S Indridason
Vilmundur Gudnason
Andrew S Levey
Source
Am J Kidney Dis. 2015 May 15;
Date
May-15-2015
Language
English
Publication Type
Article
Abstract
Chronic kidney disease (CKD) is common in the elderly, but the cause is often not identifiable. Some posit that age-related reductions in glomerular filtration rate (GFR) and increases in albuminuria are normal, whereas others suggest that they are a consequence of vascular disease.
Cross-sectional analysis of a substudy of a prospective cohort.
AGES (Age, Gene/Environment Susceptibility)-Reykjavik Study.
Exposure to higher blood pressure in midlife.
Measured GFR using plasma clearance of iohexol and urine albumin-creatinine ratio.
GFR was measured in 805 participants with mean age in midlife and late life of 51.0±5.8 and 80.8±4.0 (SD) years, respectively. Mean measured GFR was 62.4±16.5mL/min/1.73m(2) and median albuminuria was 8.0 (IQR, 5.4-16.5) mg/g. Higher midlife systolic and diastolic blood pressures were associated with lower later-life GFRs. Associations persisted after adjustment. Higher midlife systolic and diastolic blood pressures were also associated with higher albumin-creatinine ratios, and associations remained significant even after adjustment.
This is a study of survivors, and people who agreed to participate in this study were healthier than those who refused. Blood pressure may encompass effects of the other risk factors. Results may not be generalizable to populations of other races. We were not able to adjust for measured GFR or albuminuria at the midlife visit.
Factors other than advanced age may account for the high prevalence of CKD in the elderly. Midlife factors are potential contributing factors to late-life kidney disease. Further studies are needed to identify and treat midlife modifiable factors to prevent the development of CKD.
PubMed ID
25987258 View in PubMed
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12 records – page 1 of 2.