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Josef Coresh - One of the best experts on this subject based on the ideXlab platform.
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a bidirectional mendelian randomization study supports causal effects of Kidney Function on blood pressure
Kidney International, 2020Co-Authors: Josef Coresh, Alexander Teumer, Cristian Pattaro, Anna Köttgen, Harold Snieder, Morgan E Grams, Eric Boerwinkle, Nilanjan ChatterjeeAbstract:Blood pressure and Kidney Function have a bidirectional relation. Hypertension has long been considered as a risk factor for Kidney Function decline. However, whether intensive blood pressure control could promote Kidney health has been uncertain. The Kidney is known to have a major role in affecting blood pressure through sodium extraction and regulating electrolyte balance. This bidirectional relation makes causal inference between these two traits difficult. Therefore, to examine the causal relations between these two traits, we performed two-sample Mendelian randomization analyses using summary statistics of large-scale genome-wide association studies. We selected genetic instruments more likely to be specific for Kidney Function using meta-analyses of complementary Kidney Function biomarkers (glomerular filtration rate estimated from serum creatinine [eGFRcr], and blood urea nitrogen from the CKDGen Consortium). Systolic and diastolic blood pressure summary statistics were from the International Consortium for Blood Pressure and UK Biobank. Significant evidence supported the causal effects of higher Kidney Function on lower blood pressure. Based on the mode-based Mendelian randomization method, the effect estimates for one standard deviation (SD) higher in log-transformed eGFRcr was -0.17 SD unit (95 % confidence interval: -0.09 to -0.24) in systolic blood pressure and -0.15 SD unit (95% confidence interval: -0.07 to -0.22) in diastolic blood pressure. In contrast, the causal effects of blood pressure on Kidney Function were not statistically significant. Thus, our results support causal effects of higher Kidney Function on lower blood pressure and suggest preventing Kidney Function decline can reduce the public health burden of hypertension.
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Kidney Function and blood pressure a bi directional mendelian randomisation study
bioRxiv, 2019Co-Authors: Zhi Yu, Guanghao Qi, Alexander Teumer, Cristian Pattaro, Harold Snieder, Morgan E Grams, Josef Coresh, Eric Boerwinkle, Anna KöttgenAbstract:OBJECTIVE: To evaluate the bi-directional causal relation between Kidney Function and blood pressure. DESIGN: Mendelian randomisation study. SETTING: We performed two-sample Mendelian randomisation analyses. Genetic instruments of Kidney Function traits were selected from summary statistics of genome-wide association studies (GWAS) of glomerular filtration rate estimated from serum creatinine (eGFRcr) and blood urea nitrogen (BUN) and were required to be associated with both eGFRcr and BUN to ensure that the instruments were more likely to represent the underlying Kidney Function. Genetic instruments of blood pressure were selected from summary statistics of GWAS of systolic and diastolic blood pressure. We investigated Mendelian randomisation hypothesis using several alternative approaches, including methods that are most robust to the presence of horizontal pleiotropy. CONCLUSIONS: Mendelian randomisation analyses support causal effects of higher Kidney Function on lower blood pressure. These results suggest preventing Kidney Function decline can reduce the public health burden of hypertension.
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Kidney Function bone mineral metabolism markers and future risk of peripheral artery disease
Atherosclerosis, 2017Co-Authors: Chao Yang, Lucia Kwak, Shoshana H Ballew, Pranav S Garimella, Bernard G Jaar, Aaron R Folsom, Gerardo Heiss, Elizabeth Selvin, Pamela L Lutsey, Josef CoreshAbstract:BACKGROUND AND AIMS Reduced Kidney Function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond Kidney Function. METHODS Using data from 12,472 participants at baseline (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of Kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus). RESULTS During a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3-8.3 for eGFR <30 and 2.4-3.5 for eGFR 30-59 vs. eGFR ≥90 mL/min/1.73 m2). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91-3.54] for B2M vs. 1.20 [0.91-1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including Kidney Function (HR 1.47 [1.11-1.94] in top quartile). CONCLUSIONS Kidney dysFunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond Kidney Function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD.
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frailty Kidney Function and polypharmacy the atherosclerosis risk in communities aric study
American Journal of Kidney Diseases, 2017Co-Authors: Shoshana H Ballew, Josef Coresh, Elizabeth Selvin, Yan Chen, Natalie Daya, Job G Godino, Gwen B Windham, Mara A Mcadamsdemarco, Morgan E GramsAbstract:Background Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney Function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of Kidney Function may be biased in frail individuals. Study Design Observational study. Setting & Participants 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011-2013). Predictors Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFR cr ) and serum cystatin C level (eGFR cys ) and urine albumin-creatinine ratio. Outcome Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). Results 341 (7%) participants were classified as frail, 1,475 (30%) had eGFR cr 2 , 2,480 (50%) had eGFR cys 2 , and 1,006 (20%) had albuminuria with albumin excretion ≥ 30mg/g. Among frail participants, prevalences of eGFR cr and eGFR cys 2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFR cr and a strong association with eGFR cys and albumin-creatinine ratio. Frail individuals with eGFR cr of 60 to 2 were frequently reclassified to lower eGFR categories using eGFR cys (49% to 45- 2 ). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of nonfrail), including classes requiring Kidney clearance (eg, digoxin) and associated with falls and subsequent complications (eg, hypnotic/sedatives and anticoagulants). Limitations Cross-sectional study design. Conclusions Frail individuals had a high prevalence of reduced Kidney Function, with large discrepancies when reduced Kidney Function was classified by eGFR cys versus eGFR cr . Given the substantial medication burden and uncertainty in chronic Kidney disease classification, confirmation of Kidney Function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population.
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short term change in Kidney Function and risk of end stage renal disease
Nephrology Dialysis Transplantation, 2012Co-Authors: Tanvir Chowdhury Turin, Josef Coresh, Marcello Tonelli, Paul E Stevens, Paul E De Jong, Christopher K T Farmer, Kunihiro Matsushita, Brenda R HemmelgarnAbstract:Background. It is unclear what degree of change in the eGFR over a 1-year period indicates clinically significant progression, and whether this change adds additional information beyond that obtained by a single eGFR measure alone. Methods. We included 598 397 adults who had at least two outpatient eGFR measurements (at least 6 months apart) during 1-year accrual period in Alberta, Canada. Change in Kidney Function (using the first and last eGFR) was defined by change in Kidney Function category with confirmation based on percent (%) change in eGFR [(last eGFR - first eGFR)/first eGFR 100]. The groups for change in Kidney Function were thus defined as: ocertain drop' (drop in CKD category with >= 25 decrease in the eGFR); ouncertain drop' (drop in CKD category with = 25 increase in the eGFR). Adjusted end-stage renal disease (ESRD) rates (per 1000 person-years) for each group of change in Kidney Function were calculated using Poisson regression. Adjusted risks of ESRD associated with change in Kidney Function, in reference to stable Kidney Function, were estimated. Results. Among the 598 397 participants, 74.8 (n = 447 570) had stable (no change in CKD category), 3.3 (n = 19 591) had a certain drop and 3.7 (n = 22 171) had a certain rise in Kidney Function. Participants who experienced a certain change in Kidney Function (both drop and rise) were older, more likely to be female, and had a higher prevalence of comorbidities, in comparison with those with stable Kidney Function. There were 1966 (0.3) ESRD events over a median follow-up of 3.5 years. Compared with participants with stable Kidney Function, after adjustment for covariates, and the first eGFR measurement, those with certain drop had 5-fold increased risk of ESRD (HR: 5.11; 95 CI: 4.565.71), whereas those with an uncertain drop had 2-fold increased risk (HR: 2.13; 95 CI: 1.842.47). After adjustment for the eGFR and covariates at the last visit, neither a certain nor uncertain drop in the eGFR was associated with an increased ESRD risk. The ESRD risk associated with the last eGFR level, adjusted for the slope over time, were 2.89 (95 CI: 2.35-3.55), 10.98 (95 CI: 8.69-13.87), 35.20 (95 CI: 27.95-44.32) and 147.96 (116.92-187.23) for categories 2, 3a, 3b and 4, respectively, in reference to category 1. Conclusions. A change in eGFR category accompanied by >= 25 decline (certain drop) is associated with increased ESRD risk. However, this elevated risk is captured by patient characteristics and eGFR at the last visit, suggesting that eGFR trajectories based on more than two serum creatinine measurements over a period longer than 1 year are required to determine ESRD risk and allow more reliable risk prediction.
Arfan M Ikram - One of the best experts on this subject based on the ideXlab platform.
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the association of thyroid Function and the risk of Kidney Function decline a population based cohort study
European Journal of Endocrinology, 2016Co-Authors: Layal Chaker, Sanaz Sedaghat, Arfan M Ikram, Albert Hofman, Ewout J Hoorn, Oscar H Franco, Abbas Dehghan, Wendy Den P J Elzen, Jacobijn Gussekloo, Robin P PeetersAbstract:Objectives: Thyroid dysFunction has been associated with Kidney Function decline, but mainly in cross-sectional studies. Therefore, we aimed to determine the association between thyroid and Kidney Function in a prospective population-based cohort study longitudinally. Design: Prospective cohort study. Methods: Participants aged ≥45 years from the Rotterdam Study with thyroid and Kidney Function assessment were included. Kidney Function and new onset chronic Kidney disease (CKD) were defined using estimated glomerular filtration ate (eGFR), with CKD defined as eGFR <60 mL/min/1.73 m2 according to the CKD-EPI formula. Results: We included 5103 participants (mean age of 63.6 years) with a mean follow-up of 8.1 years. Cross-sectionally, higher TSH levels were associated with lower eGFR (Beta (β): ?1.75 mL/min; 95% confidence interval (CI): ?2.17, ?1.33), in multivariable models adjusting for several cardiovascular risk factors including smoking, hypertension and history of coronary heart disease among others. In contrast, longitudinally, higher TSH levels were associated with less annual eGFR decline (β: ?0.06 mL/min; CI: ?0.11, ?0.01) and lower CKD incidence (odds ratio 0.85, CI; 0.75, 0.96). Compared with euthyroid participants, subclinical hyperthyroid individuals had an increased risk for CKD whereas hypothyroid individuals had a decreased risk (P for trend = 0.04). Conclusions: Hyperactive thyroid Function is associated with increased risk of Kidney Function decline while hypothyroidism is associated with a decreased CKD risk. More insight is needed in the pathophysiological pathways connecting high thyroid Function and Kidney Function decline.
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arterial stiffness and decline in Kidney Function
Clinical Journal of The American Society of Nephrology, 2015Co-Authors: Sanaz Sedaghat, Arfan M Ikram, Albert Hofman, Francesco U S Mattaceraso, Ewout J Hoorn, Andre G Uitterlinden, Oscar H Franco, Abbas DehghanAbstract:Background and objectives The independent link between arterial stiffness and CKD remains unknown. We investigated the association of indicators of arterial stiffness with decline in Kidney Function. Design, setting, participants, & measurements We studied 3666 participants (mean age =65 years old; 58% women) from the Rotterdam Study. Pulse pressure (PP), carotid stiffness, and pulse wave velocity (PWV) were measured. We created genetic risk scores for PP and PWV. Annual declines in Kidney Function and incident CKD were assessed using eGFR. To put our findings in context of the literature, we performed a meta-analysis of the available population–based studies. Results After a median (interquartile range) follow–up time of 11 (10.7–11.3) years, 601 participants with incident CKD were recognized. In the model adjusted for age, sex, mean arterial pressure, heart rate, and baseline GFR, each SD higher PP was associated with 0.15-ml/min per 1.73 m 2 steeper annual eGFR decline (95% confidence interval [95% CI], 0.10 to 0.20) and 11% higher risk of incident CKD (95% CI, 1.05 to 1.18). Each SD greater carotid stiffness was associated with 0.08-ml/min per 1.73 m 2 steeper annual eGFR decline (95% CI, 0.04 to 0.13) and 13% higher risk of incident CKD (95% CI, 1.05 to 1.22). Each SD higher PWV was associated with 7% higher risk of incident CKD (95% CI, 1.00 to 1.14). Incorporating our findings in a meta-analysis, each SD higher PP and PWV were associated with 16% (95% CI, 1.12 to 1.21) and 8% (95% CI, 1.03 to 1.14) higher risks of incident CKD. Each SD higher PP genetic risk score was associated with 0.06-ml/min per 1.73 m 2 steeper annual eGFR decline (95% CI, 0.01 to 0.10) and 8% higher risk of incident CKD (95% CI, 1.03 to 1.14). There was no association between PWV genetic risk score and Kidney Function decline. Conclusions Higher indices of arterial stiffness are associated with steeper decline in Kidney Function. This suggests that vascular stiffness could be considered as a target for delaying decline in Kidney Function.
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Kidney Function and cerebral small vessel disease in the general population
International Journal of Stroke, 2015Co-Authors: Saloua Akoudad, Sanaz Sedaghat, Aad Van Der Lugt, Arfan M Ikram, Albert Hofman, Peter J Koudstaal, Meike W VernooijAbstract:BackgroundAnatomic and hemodynamic similarities between renal and cerebral vessels suggest a tight link between Kidney disease and brain disease. Although several distinct markers are used to identify subclinical Kidney and brain disease, a comprehensive assessment of how these markers link damage at both end organs is lacking.AimTo investigate whether measures of Kidney Function were associated with cerebral small vessel disease on MRI.MethodsIn 2526 participants of the population-based Rotterdam Study, we measured urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate based on serum creatinine and cystatin C. All participants underwent brain magnetic resonance imaging. We assessed presence of cerebral small vessel disease by calculating white matter lesion volumes and rating the presence of lacunes and cerebral microbleeds. We used multivariable linear and logistic regression to investigate the association between Kidney Function and cerebral small vessel disease.ResultsWorse kidn...
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Kidney Function is related to cerebral small vessel disease
Stroke, 2008Co-Authors: Arfan M Ikram, Wiro J. Niessen, Aad Van Der Lugt, Meike W Vernooij, Albert Hofman, Monique M B BretelerAbstract:Background and Purpose— Poor Kidney Function, as measured by glomerular filtration rate (GFR), is closely associated with presence of glomerular small vessel disease. Given the hemodynamic similarities between the vascular beds of the Kidney and the brain, we hypothesized an association between Kidney Function and markers of cerebral small vessel disease on MRI. We investigated this association in a population-based study of elderly persons. Methods— We measured GFR using the Cockcroft-Gault equation in 484 participants (60 to 90 years of age) from the Rotterdam Scan Study. Using automated MRI-analysis we measured global as well as lobar and deep volumes of gray matter and white matter, and volume of WML. Lacunar infarcts were rated visually. Volumes of deep white matter and WML and presence of lacunar infarcts reflected cerebral small vessel disease. We used linear and logistic regression models to investigate the association between GFR and brain imaging parameters. Analyses were adjusted for age, sex, ...
Mark J Sarnak - One of the best experts on this subject based on the ideXlab platform.
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low serum bicarbonate and Kidney Function decline the multi ethnic study of atherosclerosis mesa
American Journal of Kidney Diseases, 2014Co-Authors: Todd H Driver, Michael G Shlipak, Ronit Katz, Bryan Kestenbaum, David S Siscovick, Mark J Sarnak, Leonard Goldenstein, Andrew N Hoofnagle, Ian H De BoerAbstract:Background Among populations with established chronic Kidney disease (CKD), metabolic acidosis is associated with more rapid progression of Kidney disease. The association of serum bicarbonate concentrations with early declines in Kidney Function is less clear. Study Design Retrospective cohort study. Setting & Participants 5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR)>60mL/min/1.73m 2 using the CKD-EPI (CKD Epidemiology Collaboration) creatinine−cystatin C equation. Predictors Serum bicarbonate concentrations. Outcomes Rapid Kidney Function decline (eGFR decline>5% per year) and incident reduced eGFR (eGFR 2 with minimum rate of eGFR loss of 1mL/min/1.73m 2 per year). Results Average bicarbonate concentration was 23.2±1.8mEq/L. 1,730 (33%) participants had rapid Kidney Function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid Kidney Function decline (95%CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95%CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level Limitations Cause of metabolic acidosis cannot be determined in this study. Conclusions Lower serum bicarbonate concentrations are associated independently with rapid Kidney Function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR>60mL/min/1.73m 2 . If confirmed, our findings suggest that metabolic acidosis may indicate either early Kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR 2 .
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blood pressure components and decline in Kidney Function in community living older adults the cardiovascular health study
American Journal of Hypertension, 2013Co-Authors: Dena E Rifkin, Michael G Shlipak, Ronit Katz, David S Siscovick, Anne B Newman, Mark J Sarnak, Linda F Fried, Michel Chonchol, Carmen A PeraltaAbstract:Chronic Kidney disease is very common in the US population, and it is present in >30% of adults over age 65.1 High blood pressure (BP) is a well-established risk factor for chronic Kidney disease and end stage renal disease in youth and middle age.2,3 Elevated pressure in the renal vasculature and consequent elevated intraglomerular pressure lead to failure of autoregulation and endothelial dysFunction and eventually to progressive glomerular and interstitial fibrosis. In contrast, data on the association of high BP with Kidney Function decline in the elderly, in whom hypertension is highly prevalent,4 are less clear.5,6 In particular, neither randomized trial data nor genome-wide association study data provide clear supporting data for associations between lower BP and reduced risk for Kidney Function decline. For example, in the placebo arm of the Systolic Hypertension in the Elderly Program, elevated systolic pressure was associated with Kidney Function decline. Because this arm only included individuals with systolic hypertension, it cannot be easily generalized to a community-dwelling older population.7 The Hypertension in the Very Elderly Trial has not reported Kidney Function outcomes. In the large International Consortium for Blood Pressure Genome-Wide Association studies, which provide analysis of associations between BP variants and cardiovascular disease, no association was seen between these variants and chronic Kidney disease.8 In addition, the relative associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) with Kidney Function decline in the elderly are uncertain. This is of particular clinical importance because hypertension in the elderly is primarily characterized by high SBP and normal to low DBP (isolated systolic hypertension [ISH]).9 In the Cardiovascular Health Study, SBP was the best predictor of cardiovascular events, not PP or DBP.10 In the Framingham Heart Study, however, the association of each BP component with cardiovascular risk varied by age; contrary to associations in young and middle age, PP was the strongest predictor of coronary heart disease in the elderly and DBP was negatively associated with risk.11 The associations of each BP component with Kidney Function decline are not well known. Recently, the American Heart Association consensus statement on treatment of hypertension in older adults highlighted this large knowledge gap.12 Therefore, we designed this study to examine the associations of SBP, DBP, and PP with Kidney Function decline using data from the Cardiovascular Health Study.
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the risk of infection related hospitalization with decreased Kidney Function
American Journal of Kidney Diseases, 2012Co-Authors: Lorien S Dalrymple, Ronit Katz, Bryan Kestenbaum, Linda P Fried, Mark J Sarnak, Ian H De Boer, Michael G ShlipakAbstract:Background Moderate Kidney disease may predispose to infection. We sought to determine whether decreased Kidney Function, estimated by serum cystatin C level, was associated with the risk of infection-related hospitalization in older individuals. Study Design Cohort study. Setting & Participants 5,142 Cardiovascular Health Study (CHS) participants with measured serum creatinine and cystatin C and without estimated glomerular filtration rate (eGFR) 2 at enrollment. Predictor The primary exposure of interest was eGFR using serum cystatin C level (eGFR SCysC ). Outcome Infection-related hospitalizations during a median follow-up of 11.5 years. Results In adjusted analyses, eGFR SCysC categories of 60-89, 45-59, and 15-44 mL/min/1.73 m 2 were associated with 16%, 37%, and 64% greater risk of all-cause infection-related hospitalization, respectively, compared with eGFR SCysC ≥90 mL/min/1.73 m 2 . When cause-specific infection was examined, eGFR SCysC of 15-44 mL/min/1.73 m 2 was associated with an 80% greater risk of pulmonary and 160% greater risk of genitourinary infection compared with eGFR SCysC ≥90 mL/min/1.73 m 2 . Limitations No measures of urinary protein, study limited to principal discharge diagnosis. Conclusions Lower Kidney Function, estimated using cystatin C level, was associated with a linear and graded risk of infection-related hospitalization. These findings highlight that even moderate degrees of decreased Kidney Function are associated with clinically significant higher risks of serious infection in older individuals.
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rapid decline of Kidney Function increases cardiovascular risk in the elderly
Journal of The American Society of Nephrology, 2009Co-Authors: Michael G Shlipak, Ronit Katz, Bryan Kestenbaum, David S Siscovick, Linda P Fried, Anne B Newman, Dena E Rifkin, Mark J SarnakAbstract:Chronic Kidney disease (CKD), defined at a specific time point, is an important risk factor for cardiovascular disease. Whether the rate of Kidney Function decline contributes additional cardiovascular risk is unknown. In the Cardiovascular Health Study, we compared the associations of changes in Kidney Function during the first 7 yr with the incidence of heart failure (HF), myocardial infarction (MI), stroke, and peripheral arterial disease (PAD) during the subsequent 8 yr. We defined a rapid decline in cystatin C–based estimated GFR as >3 ml/min per 1.73 m2/yr, on the basis of determination at baseline, year 3, and year 7. Among eligible participants, 1083 (24%) had rapid Kidney decline. The incidence of each type of cardiovascular event was significantly higher among patients with rapid decline (all P < 0.001). After multivariate adjustment for demographics, cardiovascular disease risk factors, and baseline Kidney Function, rapid Kidney Function decline was significantly associated with HF (adjusted hazard ratio [HR] 1.32; 95% confidence interval [CI] 1.13 to 1.53), MI (HR 1.48; 95% CI 1.21 to 1.83), and PAD (HR 1.67; 95% CI 1.02 to 2.75) but not with stroke (HR 1.19; 95% CI 0.97 to 1.45). The association of rapid decline with each outcome did not differ by the presence or absence of CKD. In conclusion, declining Kidney Function associates with higher risk for HF, MI, and PAD among patients with or without CKD.
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rapid Kidney Function decline and mortality risk in older adults
JAMA Internal Medicine, 2008Co-Authors: Dena E Rifkin, Michael G Shlipak, Ronit Katz, David S Siscovick, Anne B Newman, Linda F Fried, Michel Chonchol, Mark J SarnakAbstract:Background: Impaired Kidney Function is associated with increased mortality risk in older adults. It remains unknown, however, whether longitudinal declines in Kidney Function are independently associated with increased cardiovascular and all-cause mortality in older adults. Methods: The Cardiovascular Health Study evaluated a cohort of community-dwelling older adults enrolled from 1989 to 1993 in 4 US communities with follow-up through 2005. Among 4380 participants, the slope of annual decline in estimated glomerular filtration rate (eGFR) was estimated using both serum creatinine (eGFRcreat) and cystatin C (eGFRcys) rates, which were measured at baseline, year 3, and year 7 of follow-up. Rapid decline in eGFR was defined as a loss greater than 3 mL/min/1.73 m 2 per year, and cardiovascular and all-cause mortality were assessed over a mean of 9.9 years of follow-up. Results: Mean (SD) levels of creatinine and cystatin C were 0.93 (0.30) mg/dL and 1.03 (0.25) mg/L, respectively; mean (SD) eGFRcreat and eGFRcys were 79 (23) mL/min/1.73 m 2 and 79 (19) mL/min/1.73 m 2 , respectively. Individuals with rapid decline measured by eGFRcreat (n=714; 16%) had increased risk of cardiovascular (adjusted hazard ratio [AHR], 1.70; 95% confidence interval [CI], 1.40-2.06) and allcause (AHR, 1.73; 95% CI, 1.54-1.94) mortality. Individuals with rapid decline measured by eGFRcys (n=1083; 25%) also had increased risk of cardiovascular (AHR, 1.53; 95% CI, 1.29-1.80) and all-cause (AHR, 1.53; 95% CI, 1.381.69) mortality. The association of rapid decline in eGFR with elevated mortality risk did not differ across subgroups based on baseline Kidney Function, age, sex, race, or prevalent coronary heart disease. Conclusion: Rapid decline in eGFR is associated with an increased risk of cardiovascular and all-cause mortality in older adults, independent of baseline eGFR and other demographic variables.
Albert Hofman - One of the best experts on this subject based on the ideXlab platform.
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the association of thyroid Function and the risk of Kidney Function decline a population based cohort study
European Journal of Endocrinology, 2016Co-Authors: Layal Chaker, Sanaz Sedaghat, Arfan M Ikram, Albert Hofman, Ewout J Hoorn, Oscar H Franco, Abbas Dehghan, Wendy Den P J Elzen, Jacobijn Gussekloo, Robin P PeetersAbstract:Objectives: Thyroid dysFunction has been associated with Kidney Function decline, but mainly in cross-sectional studies. Therefore, we aimed to determine the association between thyroid and Kidney Function in a prospective population-based cohort study longitudinally. Design: Prospective cohort study. Methods: Participants aged ≥45 years from the Rotterdam Study with thyroid and Kidney Function assessment were included. Kidney Function and new onset chronic Kidney disease (CKD) were defined using estimated glomerular filtration ate (eGFR), with CKD defined as eGFR <60 mL/min/1.73 m2 according to the CKD-EPI formula. Results: We included 5103 participants (mean age of 63.6 years) with a mean follow-up of 8.1 years. Cross-sectionally, higher TSH levels were associated with lower eGFR (Beta (β): ?1.75 mL/min; 95% confidence interval (CI): ?2.17, ?1.33), in multivariable models adjusting for several cardiovascular risk factors including smoking, hypertension and history of coronary heart disease among others. In contrast, longitudinally, higher TSH levels were associated with less annual eGFR decline (β: ?0.06 mL/min; CI: ?0.11, ?0.01) and lower CKD incidence (odds ratio 0.85, CI; 0.75, 0.96). Compared with euthyroid participants, subclinical hyperthyroid individuals had an increased risk for CKD whereas hypothyroid individuals had a decreased risk (P for trend = 0.04). Conclusions: Hyperactive thyroid Function is associated with increased risk of Kidney Function decline while hypothyroidism is associated with a decreased CKD risk. More insight is needed in the pathophysiological pathways connecting high thyroid Function and Kidney Function decline.
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arterial stiffness and decline in Kidney Function
Clinical Journal of The American Society of Nephrology, 2015Co-Authors: Sanaz Sedaghat, Arfan M Ikram, Albert Hofman, Francesco U S Mattaceraso, Ewout J Hoorn, Andre G Uitterlinden, Oscar H Franco, Abbas DehghanAbstract:Background and objectives The independent link between arterial stiffness and CKD remains unknown. We investigated the association of indicators of arterial stiffness with decline in Kidney Function. Design, setting, participants, & measurements We studied 3666 participants (mean age =65 years old; 58% women) from the Rotterdam Study. Pulse pressure (PP), carotid stiffness, and pulse wave velocity (PWV) were measured. We created genetic risk scores for PP and PWV. Annual declines in Kidney Function and incident CKD were assessed using eGFR. To put our findings in context of the literature, we performed a meta-analysis of the available population–based studies. Results After a median (interquartile range) follow–up time of 11 (10.7–11.3) years, 601 participants with incident CKD were recognized. In the model adjusted for age, sex, mean arterial pressure, heart rate, and baseline GFR, each SD higher PP was associated with 0.15-ml/min per 1.73 m 2 steeper annual eGFR decline (95% confidence interval [95% CI], 0.10 to 0.20) and 11% higher risk of incident CKD (95% CI, 1.05 to 1.18). Each SD greater carotid stiffness was associated with 0.08-ml/min per 1.73 m 2 steeper annual eGFR decline (95% CI, 0.04 to 0.13) and 13% higher risk of incident CKD (95% CI, 1.05 to 1.22). Each SD higher PWV was associated with 7% higher risk of incident CKD (95% CI, 1.00 to 1.14). Incorporating our findings in a meta-analysis, each SD higher PP and PWV were associated with 16% (95% CI, 1.12 to 1.21) and 8% (95% CI, 1.03 to 1.14) higher risks of incident CKD. Each SD higher PP genetic risk score was associated with 0.06-ml/min per 1.73 m 2 steeper annual eGFR decline (95% CI, 0.01 to 0.10) and 8% higher risk of incident CKD (95% CI, 1.03 to 1.14). There was no association between PWV genetic risk score and Kidney Function decline. Conclusions Higher indices of arterial stiffness are associated with steeper decline in Kidney Function. This suggests that vascular stiffness could be considered as a target for delaying decline in Kidney Function.
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Kidney Function and cerebral small vessel disease in the general population
International Journal of Stroke, 2015Co-Authors: Saloua Akoudad, Sanaz Sedaghat, Aad Van Der Lugt, Arfan M Ikram, Albert Hofman, Peter J Koudstaal, Meike W VernooijAbstract:BackgroundAnatomic and hemodynamic similarities between renal and cerebral vessels suggest a tight link between Kidney disease and brain disease. Although several distinct markers are used to identify subclinical Kidney and brain disease, a comprehensive assessment of how these markers link damage at both end organs is lacking.AimTo investigate whether measures of Kidney Function were associated with cerebral small vessel disease on MRI.MethodsIn 2526 participants of the population-based Rotterdam Study, we measured urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate based on serum creatinine and cystatin C. All participants underwent brain magnetic resonance imaging. We assessed presence of cerebral small vessel disease by calculating white matter lesion volumes and rating the presence of lacunes and cerebral microbleeds. We used multivariable linear and logistic regression to investigate the association between Kidney Function and cerebral small vessel disease.ResultsWorse kidn...
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Kidney Function is related to cerebral small vessel disease
Stroke, 2008Co-Authors: Arfan M Ikram, Wiro J. Niessen, Aad Van Der Lugt, Meike W Vernooij, Albert Hofman, Monique M B BretelerAbstract:Background and Purpose— Poor Kidney Function, as measured by glomerular filtration rate (GFR), is closely associated with presence of glomerular small vessel disease. Given the hemodynamic similarities between the vascular beds of the Kidney and the brain, we hypothesized an association between Kidney Function and markers of cerebral small vessel disease on MRI. We investigated this association in a population-based study of elderly persons. Methods— We measured GFR using the Cockcroft-Gault equation in 484 participants (60 to 90 years of age) from the Rotterdam Scan Study. Using automated MRI-analysis we measured global as well as lobar and deep volumes of gray matter and white matter, and volume of WML. Lacunar infarcts were rated visually. Volumes of deep white matter and WML and presence of lacunar infarcts reflected cerebral small vessel disease. We used linear and logistic regression models to investigate the association between GFR and brain imaging parameters. Analyses were adjusted for age, sex, ...
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Kidney Function gait pattern and fall in the general population a cohort study
Nephrology Dialysis Transplantation, 2018Co-Authors: Sanaz Sedaghat, Ewout J Hoorn, Oscar H Franco, Abbas Dehghan, Sirwan K L Darweesh, Vincentius J A Verlinden, Jos N Van Der Geest, Mohammad Arfan IkramAbstract:Background Gait disturbance is proposed as a mechanism for higher risk of fall in Kidney disease patients. We investigated the association of Kidney Function with gait pattern in the general population and tested whether the association between impaired Kidney Function and fall is more pronounced in subjects with lower gait Function. Methods We included 1430 participants (mean age: 60 years) from the Rotterdam Study. Kidney Function was assessed using estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). We assessed global gait, gait velocity and seven independent gait domains: Rhythm, Phases, Variability, Pace, Tandem, Turning and Base of Support. Regression models adjusted for cardiometabolic and neurological factors were used. We evaluated whether participants with impaired Kidney Function and impaired gait fell more in the previous year. Results The study population had a median (interquartile range) ACR of 3.6 (2.5-6.2) mg/g and mean ± SD eGFR of 87.6 ± 15 mL/min/1.73 m2. Higher ACR and lower eGFR were associated with lower global gait score [per doubling of ACR: -0.10, 95% confidence interval (CI): -0.14 to -0.06, and per SD eGFR:-0.09, 95% CI: -0.14 to -0.03] and slower gait speed (ACR: -1.44 cm/s, CI: -2.12 to -0.76; eGFR: -1.55 cm/s, CI: -2.43 to -0.67). Worse Kidney Function was associated with lower scores in Variability domain. The association between impaired Kidney Function and history of fall was present only in participants with lower gait scores [odds ratio (95% CI): ACR: 1.34 (1.09-1.65); eGFR: 1.58 (1.07-2.33)]. Conclusions We observed a graded association between lower Kidney Function and impaired gait suggesting that individuals with decreased Kidney Function, even at an early stage, need to be evaluated for gait abnormalities and might benefit from fall prevention programmes.
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the association of thyroid Function and the risk of Kidney Function decline a population based cohort study
European Journal of Endocrinology, 2016Co-Authors: Layal Chaker, Sanaz Sedaghat, Arfan M Ikram, Albert Hofman, Ewout J Hoorn, Oscar H Franco, Abbas Dehghan, Wendy Den P J Elzen, Jacobijn Gussekloo, Robin P PeetersAbstract:Objectives: Thyroid dysFunction has been associated with Kidney Function decline, but mainly in cross-sectional studies. Therefore, we aimed to determine the association between thyroid and Kidney Function in a prospective population-based cohort study longitudinally. Design: Prospective cohort study. Methods: Participants aged ≥45 years from the Rotterdam Study with thyroid and Kidney Function assessment were included. Kidney Function and new onset chronic Kidney disease (CKD) were defined using estimated glomerular filtration ate (eGFR), with CKD defined as eGFR <60 mL/min/1.73 m2 according to the CKD-EPI formula. Results: We included 5103 participants (mean age of 63.6 years) with a mean follow-up of 8.1 years. Cross-sectionally, higher TSH levels were associated with lower eGFR (Beta (β): ?1.75 mL/min; 95% confidence interval (CI): ?2.17, ?1.33), in multivariable models adjusting for several cardiovascular risk factors including smoking, hypertension and history of coronary heart disease among others. In contrast, longitudinally, higher TSH levels were associated with less annual eGFR decline (β: ?0.06 mL/min; CI: ?0.11, ?0.01) and lower CKD incidence (odds ratio 0.85, CI; 0.75, 0.96). Compared with euthyroid participants, subclinical hyperthyroid individuals had an increased risk for CKD whereas hypothyroid individuals had a decreased risk (P for trend = 0.04). Conclusions: Hyperactive thyroid Function is associated with increased risk of Kidney Function decline while hypothyroidism is associated with a decreased CKD risk. More insight is needed in the pathophysiological pathways connecting high thyroid Function and Kidney Function decline.
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arterial stiffness and decline in Kidney Function
Clinical Journal of The American Society of Nephrology, 2015Co-Authors: Sanaz Sedaghat, Arfan M Ikram, Albert Hofman, Francesco U S Mattaceraso, Ewout J Hoorn, Andre G Uitterlinden, Oscar H Franco, Abbas DehghanAbstract:Background and objectives The independent link between arterial stiffness and CKD remains unknown. We investigated the association of indicators of arterial stiffness with decline in Kidney Function. Design, setting, participants, & measurements We studied 3666 participants (mean age =65 years old; 58% women) from the Rotterdam Study. Pulse pressure (PP), carotid stiffness, and pulse wave velocity (PWV) were measured. We created genetic risk scores for PP and PWV. Annual declines in Kidney Function and incident CKD were assessed using eGFR. To put our findings in context of the literature, we performed a meta-analysis of the available population–based studies. Results After a median (interquartile range) follow–up time of 11 (10.7–11.3) years, 601 participants with incident CKD were recognized. In the model adjusted for age, sex, mean arterial pressure, heart rate, and baseline GFR, each SD higher PP was associated with 0.15-ml/min per 1.73 m 2 steeper annual eGFR decline (95% confidence interval [95% CI], 0.10 to 0.20) and 11% higher risk of incident CKD (95% CI, 1.05 to 1.18). Each SD greater carotid stiffness was associated with 0.08-ml/min per 1.73 m 2 steeper annual eGFR decline (95% CI, 0.04 to 0.13) and 13% higher risk of incident CKD (95% CI, 1.05 to 1.22). Each SD higher PWV was associated with 7% higher risk of incident CKD (95% CI, 1.00 to 1.14). Incorporating our findings in a meta-analysis, each SD higher PP and PWV were associated with 16% (95% CI, 1.12 to 1.21) and 8% (95% CI, 1.03 to 1.14) higher risks of incident CKD. Each SD higher PP genetic risk score was associated with 0.06-ml/min per 1.73 m 2 steeper annual eGFR decline (95% CI, 0.01 to 0.10) and 8% higher risk of incident CKD (95% CI, 1.03 to 1.14). There was no association between PWV genetic risk score and Kidney Function decline. Conclusions Higher indices of arterial stiffness are associated with steeper decline in Kidney Function. This suggests that vascular stiffness could be considered as a target for delaying decline in Kidney Function.
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Kidney Function and cerebral small vessel disease in the general population
International Journal of Stroke, 2015Co-Authors: Saloua Akoudad, Sanaz Sedaghat, Aad Van Der Lugt, Arfan M Ikram, Albert Hofman, Peter J Koudstaal, Meike W VernooijAbstract:BackgroundAnatomic and hemodynamic similarities between renal and cerebral vessels suggest a tight link between Kidney disease and brain disease. Although several distinct markers are used to identify subclinical Kidney and brain disease, a comprehensive assessment of how these markers link damage at both end organs is lacking.AimTo investigate whether measures of Kidney Function were associated with cerebral small vessel disease on MRI.MethodsIn 2526 participants of the population-based Rotterdam Study, we measured urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate based on serum creatinine and cystatin C. All participants underwent brain magnetic resonance imaging. We assessed presence of cerebral small vessel disease by calculating white matter lesion volumes and rating the presence of lacunes and cerebral microbleeds. We used multivariable linear and logistic regression to investigate the association between Kidney Function and cerebral small vessel disease.ResultsWorse kidn...
