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Magdalena Madero,
Carmen Peralta,
Ronit Katz,
Robert Canada,
Linda Fried,
Samer Najjar,
Michael Shlipak,
Eleanor Simonsick,
Edward Lakatta,
Kushang Patel,
Dena Rifkin,
Marquis Hawkins,
Anne Newman, Mark Sarnak
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ABSTRACT: BACKGROUND AND OBJECTIVE: The association of large arterial rigidity and kidney function decline in longitudinal analyses is not well established. This study evaluated the association of aortic pulse wave velocity (aPWV) and pulse pressure (PP) with rapid kidney function decline and incident CKD in the Health, Aging and Body Composition study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants were 2129 older adults with a baseline measurement of aPWV, PP, and cystatin C and at least one additional measurement of cystatin C, either at year 3 or year 10. Outcomes were rapid kidney function decline (estimated GFR(cysC) loss of >3 ml/min per 1.73 m(2) per year) and incident CKD (eGFR(cysC) < 60 ml/min per 1.73 m(2) in participants with baseline estimated GFR > 60 ml/min per 1.73 m(2)). Multivariate regression models were used to evaluate association of aPWV and PP with each outcome. RESULTS: Mean (SD) baseline estimated GFR(cysC) was 79±29 ml/min per 1.73 m(2). Median follow-up duration was 8.9 years. In multivariable analyses, aPWV was not associated with rapid decline (odds ratio [OR], 95% confidence interval [CI] 1.16, 0.89-1.52) but was associated with incident CKD (incident rate ratio [IRR], 95% CI, 1.39, 1.09-1.77) and PP was associated with both rapid decline (OR, 95% CI 1.10, 1.04-1.16) and incident CKD (IRR, 95% CI, 1.06, 1.01-1.11). CONCLUSIONS: Large arterial stiffness assessed by aPWV and pulsatility assessed by PP were associated with incident CKD among older adults. Pulsatility assessed by PP was associated with rapid kidney function decline and incident CKD. Future research should determine whether interventions targeting arterial rigidity will prevent CKD development and progression.
Clinical Journal of the American Society of Nephrology 12/2012; · 5.23 Impact Factor
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ABSTRACT: BACKGROUND: Whether elevations in levels of urinary biomarkers of tubular injury (urine neutrophil gelatinase-associated lipocalin [NGAL] and kidney injury molecule 1 [KIM-1]) are associated with future risk of kidney disease has not been investigated. STUDY DESIGN: 1:1 nested case-control study. SETTING & PARTICIPANTS: 686 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). PREDICTOR: NGAL and KIM-1 were measured at baseline, expressed as log-transformed continuous variables, and categorized into deciles. OUTCOMES: Kidney function was estimated by cystatin C level using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Incident CKD stage 3 was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) and an eGFR decrease >1 mL/min/1.73 m(2) per year, and rapid kidney function decrease was defined as decrease ≥3 mL/min/1.73 m(2) per year. MEASUREMENTS: Cases were defined as persons with eGFR >60 mL/min/1.73 m(2) who subsequently developed incident CKD stage 3 and/or had rapid kidney function decrease by the MESA year-5 visit. Controls were matched for age, sex, race, diabetes, and baseline eGFR. We adjusted for age, hypertension, and presence of albuminuria (albumin-creatinine ratio ≥30 mg/g). RESULTS: Of 343 cases, 145 had incident CKD stage 3, 141 had rapid kidney function decrease, and 57 had both. Mean eGFR for controls was 81 ± 10 mL/min/1.73 m(2) at baseline and 80 ± 10 mL/min/1.73 m(2) at follow-up compared with 82 ± 13 and 58 ± 10 mL/min/1.73 m(2) for cases. Each doubling of KIM-1 level (in picograms per milliliter) was associated with an OR of 1.15 (95% CI, 1.02-1.29) for incident CKD stage 3 and/or rapid kidney function decrease. Compared with the lowest 90%, the highest decile of KIM-1 level was associated with an OR of 2.02 (95% CI, 1.15-3.56) for the outcome; these associations were independent of albuminuria. NGAL levels (in nanograms per milliliter) were not associated with incident CKD stage 3 and/or rapid kidney function decrease (OR, 1.04; 95% CI, 0.99-1.10). Results were similar when KIM-1 and NGAL levels were standardized for urine creatinine. LIMITATIONS: The case-control design limits the ability to account for persons who died or were not available for follow-up. CONCLUSIONS: Urinary KIM-1 level is associated with future risk of kidney disease independent of albuminuria. Urinary biomarkers of tubular injury are a promising tool for identifying persons at risk of CKD.
American Journal of Kidney Diseases 06/2012; · 5.43 Impact Factor
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ABSTRACT: The strength and direction of the associations between inflammation and coagulation biomarkers with kidney disease onset and progression remain unclear, especially in a population-based setting.
Prospective observational study.
4,966 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with a cystatin C-based estimate of glomerular filtration rate (eGFR(cys)) >60 mL/min/1.73 m(2) and at least one follow-up measurement of kidney function. All participants were free of cardiovascular disease at entry.
We evaluated the associations of C-reactive protein (CRP), interleukin 6 (IL-6), fibrinogen, factor VIII, and d-dimer levels with kidney function decrease.
Kidney function decrease was assessed primarily by repeated measurements of eGFR(cys) over 5 years. Rapid decrease in kidney function was defined as eGFR decrease >3 mL/min/1.73 m(2) per year. Incident low eGFR was defined as the onset of eGFR(cys) <60 mL/min/1.73 m(2) at any follow-up examination and eGFR(cys) decrease ≥1 mL/min/1.73 m(2) per year.
Mean age was 60 years, 39% were white, 52% were women, and 11% had diabetes. Mean eGFR(cys) was 96 mL/min/1.73 m(2) and 7% had albuminuria. Median follow-up was 4.77 years. Higher factor VIII levels (per 1 standard deviation [SD] of biomarker) had the strongest association with kidney function decrease (β = -0.25; 95% CI, -0.38 to -0.12; P < 0.001), followed by IL-6 (β = -0.16; 95% CI, -0.29 to -0.03; P = 0.01), CRP (β = -0.09; 95% CI, -0.22 to 0.03; P = 0.1), and fibrinogen levels (β = -0.09; 95% CI, -0.22 to 0.04; P = 0.2). Each 1-SD higher concentration of IL-6 (OR, 1.15; 95% CI, 1.07-1.23), factor VIII (OR, 1.11; 95% CI, 1.03-1.18), and CRP (OR, 1.09; 95% CI, 1.02-1.16) at baseline was associated significantly with rapid kidney function decrease. Only IL-6 level was associated significantly with incident low eGFR (OR, 1.09; 95% CI, 1.00-1.19).
Observational study design and absence of measured GFR.
Inflammation and coagulation biomarkers are associated with decreasing kidney function in ambulatory adults without established cardiovascular disease or chronic kidney disease.
American Journal of Kidney Diseases 05/2012; 60(2):225-32. · 5.43 Impact Factor
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Carmen A Peralta,
Ronit Katz,
Michael Shlipak,
Ruth Dubin,
Ian DeBoer,
Nancy Jenny,
Annette Fitzpatrick,
Carol Koro,
Bryan Kestenbaum,
Joachim Ix, Mark Sarnak,
Mary Cushman
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ABSTRACT: Whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels are associated with kidney function decline has not been well studied.
We investigated associations of Lp-PLA(2) antigen and activity with kidney function decline and rapid decline over 5.7 years in the Cardiovascular Health Study (n = 4,359). We estimated kidney function by cystatin C (eGFRcys) in repeated measures, and defined rapid decline as ≥3 ml/min/1.73 m(2) per year. We stratified by baseline preserved GFR (≥60 ml/min/1.73 m(2)).
Mean age was 72 ± 5 years. Average eGFRcys decline was -1.79 ml/min/1.73 m(2) (SD = 2.60) per year. Among persons with preserved GFR, compared to the lowest quartile of Lp-PLA(2) antigen, eGFRcys decline was faster among persons in the second, β -0.31 (95% CI -0.52, -0.10), third -0.19 (-0.41, 0.02) and fourth quartiles -0.26 (-0.48, -0.04) after full adjustment. Persons in the highest quartile of Lp-PLA(2) antigen had increased odds of rapid decline 1.34 (1.03, 1.75), compared to the lowest. There was no significant association between levels of Lp-PLA(2) activity and eGFRcys decline or rapid decline. Associations were not statistically significant among persons with low eGFR (<60 ml/min/1.73 m(2)) at baseline.
Higher levels of Lp-PLA(2) antigen but not activity were significantly associated with faster rates of kidney function decline. These findings may suggest a novel vascular pathway for kidney disease progression.
American Journal of Nephrology 11/2011; 34(6):512-8. · 2.54 Impact Factor
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ABSTRACT: Whether the rate of kidney function decline before the onset of CKD differs among racial and ethnic groups remains unclear. Here, we evaluated kidney function decline and incident CKD among white, black, Hispanic, and Chinese participants in the Multi-Ethnic Study of Atherosclerosis (MESA) during 5 years of follow-up. We estimated GFR using both cystatin C (eGFRcys) and creatinine (eGFRcreat). The definition of incident CKD required eGFRcys <60 ml/min per 1.73 m(2) and a decline in eGFRcys ≥1 ml/min per year. Among participants with eGFRcreat >60 ml/min per 1.73 m(2) at baseline, blacks had a significantly higher rate of kidney function decline than whites (0.31 ml/min per 1.73 m(2)/yr faster on average, P=0.001), even after adjusting for multiple potential confounders. Among Hispanics, Dominicans and Puerto Ricans had faster rates of decline than whites (0.55 and 0.47 ml/min per 1.73 m(2)/yr faster, respectively). Mexicans, South Americans, or other Hispanics had similar rates of decline compared to whites. We did not detect significant differences in the rates of kidney function decline among Chinese and white participants. Among those with normal or near-normal kidney function at baseline, blacks and Hispanics had the highest rates of incident CKD during follow-up. Adjustment for comorbidities attenuated some of these differences. In conclusion, the average rate of kidney function decline before the onset of CKD differs among racial and ethnic groups. Traditional risk factors do not explain these differences fully, highlighting the need to explore these disparities.
Journal of the American Society of Nephrology 06/2011; 22(7):1327-34. · 9.66 Impact Factor
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Brad C Astor,
Kunihiro Matsushita,
Ron T Gansevoort,
Marije van der Velde,
Mark Woodward,
Andrew S Levey,
Paul E de Jong,
Josef Coresh,
Meguid El-Nahas,
Kai-Uwe Eckardt, [......],
Barry Brenner,
Dick de Zeeuw,
Peter Rossing,
Hans-Henrik Parving,
Priscilla Auguste,
Kasper Veldhuis,
Yaping Wang,
Laura Camarata,
Beverly Thomas,
Tom Manley
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ABSTRACT: We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected for CKD of diverse etiology. After adjustment for potential confounders and albuminuria, we found that a 15 ml/min per 1.73 m² lower eGFR below a threshold of 45 ml/min per 1.73 m² was significantly associated with mortality and ESRD (pooled hazard ratios (HRs) of 1.47 and 6.24, respectively). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eightfold higher albumin- or protein-to-creatinine ratio was significantly associated with mortality (pooled HR 1.40) without evidence of significant heterogeneity and with ESRD (pooled HR 3.04), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD, with the associations stronger for ESRD than for mortality. Thus, these relationships are consistent with CKD stage classifications based on eGFR and suggest that albuminuria provides additional prognostic information among individuals with CKD.
Kidney International 02/2011; 79(12):1331-40. · 6.61 Impact Factor
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ABSTRACT: Most deaths in autosomal dominant polycystic kidney disease (ADPKD) are attributable to cardiovascular disease (CVD). We examined novel CVD biomarkers in different stages of ADPKD.
We recruited 50 hypertensive subjects with ADPKD with estimated GFR (eGFR) of >60 ml/min per 1.73 m(2); 52 hypertensive subjects with ADPKD with eGFR of 25 to 60 ml/min per 1.73 m(2); 42 normotensive subjects with ADPKD and eGFR of >60 ml/min per 1.73 m(2); and 50 healthy controls. We assayed serum C-reactive protein and IL-6 as markers of inflammation; plasma 8-epi-prostaglandin F(2α (8-epi-PGF2α)) and superoxide dismutase (SOD) as markers of oxidative stress; and homeostasis model assessment (HOMA) as a measure of insulin resistance.
The hypertensive ADPKD eGFR of 25 to 60 group had higher levels of C-reactive protein and IL-6 than controls, normotensive ADPKD with eGFR of >60, and hypertensive ADPKD with eGFR of >60. The normotensive ADPKD eGFR >60, hypertensive ADPKD eGFR >60, and hypertensive ADPKD eGFR 25 to 60 groups had higher 8-epi-PGF(2α) and lower SOD than controls, with no difference between the ADPKD groups. There was no difference in HOMA levels between any of the groups. Adjustment for age, race, gender, and body mass index did not alter these relationships.
Inflammation and oxidative stress are evident early in ADPKD even with preserved kidney function. Inflammation exhibits a graded relationship with levels of kidney function, whereas oxidative stress demonstrates a threshold effect. These pathways may be therapeutic targets for CVD risk mitigation.
Clinical Journal of the American Society of Nephrology 01/2011; 6(1):7-13. · 5.23 Impact Factor
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ABSTRACT: Habitual physical activity (PA) has both physiologic and metabolic effects that may moderate the risk of kidney function decline. We tested the hypothesis that higher levels of PA are associated with a lower risk of kidney function decline using longitudinal data from a large cohort of older adults.
We studied 4011 ambulatory participants aged 65 or older from the Cardiovascular Health Study (CHS) who completed at least 2 measurements of kidney function over 7 years. We calculated a PA score (range, 2-8) by summing kilocalories expended per week (ordinal score of 1-5 from quintiles of kilocalories per week) and walking pace (ordinal score for categories of <2, 2-3, and >3 mph). Rapid decline in kidney function decline (RDKF) was defined by loss of more than 3.0 mL/min/1.73 m(2) per year in glomerular filtration rate, which we estimated by using longitudinal measurements of cystatin C levels.
A total of 958 participants had RDKF (23.9%; 4.1 events per 100 person-years). The estimated risk of RDKF was 16% in the highest PA group (score of 8) and 30% in the lowest PA group (score of 2). After multivariate adjustment, we found that the 2 highest PA groups (scores of 7-8) were associated with a 28% lower risk of RDKF (95% confidence interval, 21%-41% lower risk) than the 2 lowest PA groups (score of 2-3). Greater kilocalories of leisure-time PA and walking pace were also each associated with a lower incidence of RDKF.
Higher levels of PA are associated with a lower risk of RDKF among older adults.
Archives of internal medicine 12/2009; 169(22):2116-23. · 11.46 Impact Factor
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Anna K|[ouml]|ttgen,
Nicole L Glazer,
Abbas Dehghan,
Shih-Jen Hwang,
Ronit Katz,
Man Li,
Qiong Yang,
Vilmundur Gudnason,
Lenore J Launer,
Tamara B Harris, [......],
Andr|[eacute]| G Uitterlinden,
Cornelia M van Duijn,
Daniel I Chasman,
Guillaume Par|[eacute,
Paul M Ridker,
W H Linda Kao,
Jacqueline C Witteman,
Josef Coresh,
Michael G Shlipak,
Caroline S Fox
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ABSTRACT: Chronic kidney disease (CKD) has a heritable component and is an important global public health problem because of its high prevalence and morbidity
Nature Genetics 05/2009; 41(6):712-717. · 35.53 Impact Factor
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Anna Köttgen,
Nicole L Glazer,
Abbas Dehghan,
Shih-Jen Hwang,
Ronit Katz,
Man Li,
Qiong Yang,
Vilmundur Gudnason,
Lenore J Launer,
Tamara B Harris, [......],
André G Uitterlinden,
Cornelia M van Duijn,
Daniel I Chasman,
Guillaume Paré,
Paul M Ridker,
W H Linda Kao,
Jacqueline C Witteman,
Josef Coresh,
Michael G Shlipak,
Caroline S Fox
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ABSTRACT: Chronic kidney disease (CKD) has a heritable component and is an important global public health problem because of its high prevalence and morbidity. We conducted genome-wide association studies (GWAS) to identify susceptibility loci for glomerular filtration rate, estimated by serum creatinine (eGFRcrea) and cystatin C (eGFRcys), and CKD (eGFRcrea < 60 ml/min/1.73 m(2)) in European-ancestry participants of four population-based cohorts (ARIC, CHS, FHS, RS; n = 19,877; 2,388 CKD cases), and tested for replication in 21,466 participants (1,932 CKD cases). We identified significant SNP associations (P < 5 × 10(-8)) with CKD at the UMOD locus, with eGFRcrea at UMOD, SHROOM3 and GATM-SPATA5L1, and with eGFRcys at CST and STC1. UMOD encodes the most common protein in human urine, Tamm-Horsfall protein, and rare mutations in UMOD cause mendelian forms of kidney disease. Our findings provide new insights into CKD pathogenesis and underscore the importance of common genetic variants influencing renal function and disease.
Nature Genetics 05/2009; 41(6):712-7. · 35.53 Impact Factor
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ABSTRACT: Vascular remodeling may be a mechanism linking chronic kidney disease to cardiovascular disease. Whether early kidney dysfunction is associated with small and large arterial remodeling is not well understood. Using multivariable linear regression, back-transforming beta-coefficients to relative difference, the authors studied the association of cystatin C, creatinine-based estimated glomerular filtration rate (GFR), and albuminuria with small (SAE) and large (LAE) arterial elasticity and aortic distensibility among 6,282 participants in the Multiethnic Study of Atherosclerosis at baseline (2000-2002). Compared with the lowest quintile, higher quintiles of cystatin C were incrementally associated with lower SAE: third quintile relative difference = -5% (95% confidence interval (CI): -8, -2); fourth quintile relative difference = -10% (95% CI: -13, -8); and highest quintile relative difference = -16% (95% CI: -20, -12). By use of creatinine, the association was observed only among those with chronic kidney disease (estimated GFR, <60 mL/minute/1.73 m(2)): relative difference = -9% (95% CI: -13, -4). Albuminuria was significantly associated with lower SAE: relative difference = -6% (95% CI: -10, -1). Cystatin C was associated with lower LAE only at the highest quintile (relative difference = -3%, 95% CI: -6, 0) compared with the lowest quintile. By use of creatinine, chronic kidney disease was not independently associated with LAE (P = 0.912). Cystatin C, estimated GFR, and albuminuria were not associated with aortic distensibility (P = 0.26, 0.48, 0.45). Early kidney dysfunction is significantly associated with decreased arterial elasticity in smaller arteries and, to a lesser degree, in larger arteries.
American journal of epidemiology 01/2009; 169(6):740-8. · 5.59 Impact Factor
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ABSTRACT: Persons with early kidney disease have an increased risk of cardiovascular events and mortality, but the importance of accelerated atherosclerosis in promoting these outcomes is unclear. We therefore explored whether serum cystatin C level is associated with carotid intima-media thickness (IMT) in ambulatory adults without clinical heart disease.
Cross-sectional study.
We evaluated 6,557 ethnically diverse persons free of clinical cardiovascular disease aged 45 to 84 years at the baseline visit of the Multi-Ethnic Study of Atherosclerosis.
Kidney function was estimated by using 2 methods: serum cystatin C level and estimated glomerular filtration rate, based on creatinine and cystatin C levels.
Study outcomes were internal and common carotid IMT, measured by using high-resolution B-mode ultrasound. Multivariate linear and logistic regressions were used to evaluate the independent association of kidney function with carotid IMT.
In unadjusted linear analysis, each SD (0.23 mg/L) greater cystatin C level was associated with 0.091-mm greater internal carotid IMT (P < 0.001), but this association was diminished by 70% after adjustment for age, sex, and race/ethnicity (0.027 mm; P < 0.001) and was no longer significant after adjustment for cardiovascular risk factors (0.005 mm; P = 0.5). Similarly, the strong unadjusted associations of cystatin C level with common carotid IMT disappeared after adjustment. Chronic kidney disease, defined by using either creatinine level or cystatin C-based estimated glomerular filtration rate less than 60 mL/min/1.73 m(2), had no independent association with internal and common carotid IMT.
There were few participants with severe kidney disease.
Cystatin C level had no independent association with carotid IMT in a population free of clinical heart disease. This observation suggests that accelerated atherosclerosis is unlikely to be the primary mechanism explaining the independent association of cystatin C level with cardiovascular risk.
American Journal of Kidney Diseases 10/2008; 53(3):389-98. · 5.43 Impact Factor
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ABSTRACT: Prior studies evaluating the relationship of kidney disease with cardiovascular risk factors have been limited by their cross-sectional design. We evaluated the change in lipids, inflammatory and procoagulant biomarkers with decline in kidney function in a nested case-cohort study in the Cardiovascular Health Study, a community-based study of adults aged >65 years.
Individuals with an increase in serum creatinine >or=0.3 mg/dl (baseline to 3 years later, n = 207) were matched to controls of similar age, race, gender, diabetes and baseline serum creatinine, but whose change in creatinine was <0.3 mg/dl. Baseline and change in risk factors were analyzed with conditional logistic regression.
Changes in C-reactive protein were similar. In contrast, cases had larger increases in fibrinogen (OR 1.38 per standard deviation, 95% confidence interval 1.08-1.76) and factor VIII [1.38 (1.10-1.72)] and larger decreases in HDL [OR 0.80 (0.64, 1.00)]. Change in interleukin-6 was greater in cases than controls, but this did not persist after multivariate adjustment. However, in linear regression, change in interleukin-6 was correlated with change in creatinine.
Cardiovascular risk factors and kidney function may change concurrently. This could lead to an increased risk of cardiovascular disease as kidney function worsens.
American Journal of Nephrology 10/2008; 29(4):334-41. · 2.54 Impact Factor
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Cleveland Clinic Journal of Medicine 03/2008; 75(2):118-20. · 3.77 Impact Factor
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ABSTRACT: Protein-energy wasting and inflammation are common and associated with an increased risk of mortality in hemodialysis (HD) patients. We examined the extent to which they mediate the associations of each other with death in this population.
Retrospective analysis of the Hemodialysis (HEMO) Study data.
Prevalent HD patients.
One-thousand HEMO study participants with data available on C-reactive protein (CRP), body mass index (BMI), and serum creatinine.
None.
The associations of CRP, BMI, and serum creatinine with time to all-cause mortality separately and together in multivariate Cox models.
In 1,437 patient-years of follow-up, there were 265 (26.5%) all-cause deaths. Compared with the lowest CRP quartile, the highest quartile was associated with a hazard ratio (HR) of 2.02 (95% confidence interval [CI], 1.31-3.10) for all-cause mortality. This association of highest CRP quartile with mortality was not attenuated with further adjustment for BMI and serum creatinine (HR, 2.13; 95% CI, 1.38-3.30). When serum albumin was added to the model, the hazard of death associated with highest CRP quartile was modestly attenuated (HR, 1.88; 95% CI, 1.21-2.92). In contrast, both BMI (for each kg/m2 increase; HR, 0.94; 95% CI, 0.91-0.96 for all-cause mortality) and serum creatinine (for each mg/dL increase; HR, 0.85; 95% CI, 0.79-0.90 for all-cause mortality) had strong, independent protective effects. Further adjustment with CRP had a negligible effect on these associations.
The associations of markers of nutrition and inflammation with mortality are largely independent of each other in HD patients.
Journal of Renal Nutrition 12/2007; 17(6):372-80. · 1.57 Impact Factor
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Linda F Fried,
Mary Louise Biggs,
Michael G Shlipak,
Stephen Seliger,
Bryan Kestenbaum,
Catherine Stehman-Breen, Mark Sarnak,
David Siscovick,
Tamara Harris,
Jane Cauley,
Anne B Newman,
John Robbins
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ABSTRACT: Kidney dysfunction is associated with bone loss, and patients with ESRD have an increased risk for hip fracture. However, the association of mild to moderate kidney disease with hip fracture has not been studied previously. The association of kidney function with incident hip fracture was examined among participants in the Cardiovascular Health Study, a community-based cohort of older individuals. The primary measure of kidney function was serum cystatin C, a measure that does not depend on lean mass. Hip fractures were identified using International Classification of Diseases, Ninth Revision codes for hospitalizations. A total of 4699 individuals had cystatin C measured in 1992 to 1993 and did not have a hip fracture before cystatin C measurement. The association of kidney function with hip fracture was analyzed with Cox proportional hazards models. Analyses were conducted separately for men and women. After a mean follow-up of 7.1 yr, 195 incident hip fractures occurred in women and 79 occurred in men. Higher cystatin C levels were associated with a higher risk for fracture in women (hazard ratio [HR] 1.26; 95% confidence interval [CI] 1.14 to 1.38 per SD) and in men (HR 1.27; 95% CI 1.11 to 1.46). After multivariable adjustment, higher cystatin C levels were significantly associated with hip fracture in women (HR 1.16; 95% CI 1.01, 1.33) but not in men (HR 1.14; 95% CI 0.86 to 1.52), although the magnitude of the association was similar. Kidney dysfunction, as assessed by cystatin C, is associated with an increased risk for hip fracture. Further studies are needed to evaluate potential mediators of this relationship and to assess whether interventions can decrease this risk.
Journal of the American Society of Nephrology 02/2007; 18(1):282-6. · 9.66 Impact Factor
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Linda F Fried,
Michael G Shlipak,
Catherine Stehman-Breen,
Anuja Mittalhenkle,
Stephen Seliger, Mark Sarnak,
John Robbins,
David Siscovick,
Tamara B Harris,
Anne B Newman,
Jane A Cauley
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ABSTRACT: Results of cross-sectional analyses of the association of kidney function with bone mineral density (BMD) have been conflicting. We examined the association of cystatin-C, a new marker of kidney function that is unrelated to lean mass, with initial and follow-up BMD, in an ancillary study of the Cardiovascular Health Study, a population-based cohort of individuals > or = 65 years old.
Two years after measurement of cystatin-C and other covariates, the first BMD was measured in Pittsburgh, Pennsylvania and Davis, California, by using dual energy x-ray absorptiometry. Follow-up BMD was measured in Pittsburgh 4 years later. Associations of cystatin-C with initial BMD and the change in BMD (%/y) at the hip were examined with linear regression. Analyses were conducted separately for men and women.
In 1519 participants who had cystatin-C and initial BMD assessed, 614 had follow-up BMD. The percent annual change in BMD at the total hip by cystatin-C quartiles was -0.24, -0.13, -0.40, and -0.66%/y (first to fourth quartile) in women and -0.02, -0.30, -0.18, and -0.94%/y in men. After adjusting for potential confounders, cystatin-C was marginally associated with initial BMD in men but not women. Cystatin-C was associated with bone loss in men; after adjustment for weight loss, cystatin-C was not associated with bone loss in women.
Kidney dysfunction, as assessed by cystatin-C, is associated with a more rapid loss of BMD at the hip, especially in men. Further studies are needed to confirm these findings and to determine whether this loss leads to an elevated risk of fracture.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 07/2006; 61(7):743-8. · 4.60 Impact Factor
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Stephen L Seliger,
W T Longstreth,
Ronit Katz,
Teri Manolio,
Linda F Fried,
Michael Shlipak,
Catherine O Stehman-Breen,
Anne Newman, Mark Sarnak,
Daniel L Gillen,
Anthony Bleyer,
David S Siscovick
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ABSTRACT: Subclinical brain infarcts (SBI) are common in the elderly and are associated with covert neurologic and cognitive impairment. Although renal impairment is associated with accelerated cerebrovascular disease and an increased risk for clinically apparent brain infarct, few studies have examined the relationship between renal function and SBI, and these may have been limited by the inaccuracy of creatinine as a renal function marker. A cross-sectional study was performed among older adults in the Cardiovascular Health Study to examine associations between SBI and two serum markers of renal function: Serum creatinine (SCr) and cystatin C (CysC). Patients had cranial magnetic resonance imaging and renal markers measured in 1992 to 1993. Logistic regression was used to estimate the associations between renal function (estimated by 1/SCr and 1/CysC) and SBI, controlling for potential confounding factors. SBI were present in 789 (28.7%) of 2784 participants. A linear association with SBI was observed for 1/CysC (per 1-SD decrement; odds ratio [OR] 1.20; 95% confidence interval [CI] 1.09 to 1.32; P < 0.001) but not for 1/SCr (OR 1.08; 95% CI 0.98 to 1.19; P = 0.14), for which a quadratic U-shaped association was suggested (P = 0.004). In a model with both markers, 1/CysC was linearly associated with SBI (OR 1.26; P < 0.001), whereas 1/SCr was not (OR 1.06; P = 0.3). The prevalence of SBI was directly associated with quintile of CysC, whereas the association between SCr and SBI was U-shaped, with greater prevalence at high and low levels. Compared with creatinine, CysC, a novel marker of renal function, has a stronger and more direct association with SBI in the elderly.
Journal of the American Society of Nephrology 12/2005; 16(12):3721-7. · 9.66 Impact Factor
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ABSTRACT: The reduction of cardiovascular disease risk in kidney failure involves treatment of modifiable risk factors and provision of proven interventions to patients with established disease. Volume status management is key to blood pressure control. Statins are the agents of choice for the treatment of dyslipidemia. Target hemoglobin levels should be achieved using intravenous iron and erythropoietic agents. Combinations of calcium and noncalcium-containing phosphorus binders and vitamin D and its analogues should be used to attain target parathyroid hormone, phosphorus, and calcium phosphorus product levels. beta Blockers and aspirin are recommended in patients with ischemic heart disease and angiotensin-converting enzyme inhibitors (or angiotensin II receptor blockers), and beta blockers are recommended in patients with heart failure with reduced ejection fraction. In patients who require revascularization, studies suggest a survival benefit of coronary artery bypass graft surgery over percutaneous transluminal coronary angioplasty and coronary artery stenting.
Current Treatment Options in Cardiovascular Medicine 09/2004; 6(4):257-268.
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ABSTRACT: Because cardiovascular disease is the leading cause of death and hypoalbuminemia predicts mortality, hypoalbuminemia may be associated with atherosclerosis.
In 1,411 patients enrolled in the HEMO study, associations of albumin with the presence of coronary artery disease (CAD), cerebrovascular disease (CVD), peripheral vascular disease (PVD), and any one of the three conditions at baseline were examined using multivariable logistic regression models.
In the two-slope model, when albumin level was 3.6 g/dL (36 g/L) or greater, with each 1-g/dL (10-g/L) increase in albumin level the odds for CAD (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.17 to 0.59), PVD (OR, 0.39; 95% CI, 0.18 to 0.80), CVD (OR, 0.33; 95% CI, 0.15 to 0.73), and any one of the three conditions (OR, 0.23; 95% CI, 0.12 to 0.44) decreased. When albumin level was less than 3.6 g/dL (36 g/L), none of the conditions was statistically significantly associated with each 1-g/dL (10-g/L) increase in albumin level. When normal- and low-albumin groups were compared with each other, patients with albumin levels less than 3.6 g/dL (36 g/L) had a higher association with CAD (OR, 1.32; 95% CI, 1.03 to 1.70) and for any one of the three conditions (OR, 1.38; 95% CI, 1.07 to 1.78).
The odds for atherosclerosis linearly decreased as albumin level increased in the normal-albumin group, and a plateau was seen in the low-albumin group; however, the low-albumin group had significantly greater CAD. The nonlinearity of association of albumin level with prevalence of atherosclerosis might be due to the cross-sectional nature of the study of higher mortality with hypoalbuminemia.
American Journal of Kidney Diseases 11/2002; 40(4):721-7. · 5.43 Impact Factor
