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1.  Cis-vaccenic acid and the Framingham Risk Score predict chronic kidney disease: the Multi-ethnic Study of Atherosclerosis (MESA) 
SUMMARY
Introduction
Data on the associations of fatty acids with chronic kidney disease (CKD) are sparse.
Materials and Methods
We performed a cross-sectional study of 2792 men and women from the MESA cohort of African-American, Caucasian, Chinese and Hispanic adults without known cardiovascular disease. Plasma phospholipid fatty acid proportions were associated with estimated glomerular filtration rate (eGFR) and the albumin/creatinine ratio.
Results
Cis-vaccenic acid (18:1n-7), adjusted for other fatty acids using multivariate logistic regression (CI: 1.0–1.4), and step-wise logistic regression (CI: 1.02–1.42), was positively associated with reduced eGFR. The Framingham Risk Score, when adjusting for fatty acid proportions and demographic factors, was positively associated with CKD as measured by the eGFR and the albumin/creatinine ratio.
Discussion and Conclusions
Plasma phospholipid proportions of the18 carbon monounsaturated cis-vaccenic acid {18:1n-7}) and the Framingham Risk Score are associated with kidney function. The potential role of 18:1n-7 in the development of CKD warrants further investigation.
doi:10.1016/j.plefa.2012.02.009
PMCID: PMC3340522  PMID: 22417701
Fatty acids; chronic kidney disease; Framingham Heart Disease Risk Score; 18:1n-7; cisvaccenic acid; monounsaturated 18 carbon fatty acid
2.  Genetic variation in APOL1 and MYH9 genes is associated with chronic kidney disease among Nigerians 
Purpose
A region of chromosome 22 which includes APOL1 and MYH9 genes was recently identified as a risk locus for non-diabetic forms of kidney disease, including idiopathic and HIV associated focal segmental glomerular sclerosis and kidney disease clinically attributed to hypertension among African Americans. The purpose of the current study was therefore to examine the frequency of these variants and to determine whether they are associated with chronic kidney disease (CKD) among native Africans.
Methods
To investigate possible evidence of association between variants in these genes and non-diabetic CKD among West Africans, we performed a case/control analysis in a sample of 166 Nigerians without history of European admixture. Our study included a total of 9 variants on APOL1 (n=4) and MYH9 (n=5) genes.
Results
We observed significantly strong associations with previously reported APOL1 variants rs73885319 and rs60910145 and their two-allele “G1” haplotype (P < 0.005). We did not observe significant evidence of association between non-diabetic CKD and any of the MYH9 variants or haplotypes after accounting for multiple testing in our sample.
Conclusions
In conclusion, APOL1 risk variants are associated with non-diabetic forms of CKD among Nigerians of Yoruba ethnicity. Further information on APOL1/MYH9 variants may lead to screening programs which could lead to earlier detection and interventions for non-diabetic kidney disease.
doi:10.1007/s11255-012-0263-4
PMCID: PMC3599169  PMID: 22956460
chronic kidney disease; APOL1; MYH9; genetic renal disease
3.  Association of Pulse Pressure, Arterial Elasticity, and Endothelial Function With Kidney Function Decline Among Adults With Estimated GFR > 60 mL/min/1.73 m2: The Multi-Ethnic Study of Atherosclerosis 
Background
The association of subclinical vascular disease and early declines in kidney function has not been well studied.
Study Design
Prospective cohort study
Setting & Participants
MESA participants with eGFR ≥60 ml/min/1.73m2 with follow-up of 5 years
Predictors
Pulse pressure (pulse pressure), small and large arterial elasticity (SAE, LAE), and flow mediated dilation.
Outcomes
kidney function decline
Measurements
SAE and LAE were measured by pulse contour analysis of the radial artery. Kidney function was measured by serum creatinine- and cystatin C-based eGFR.
Results
Among 4,853 adults, higher pulse pressure and lower SAE and LAE had independent and linear associations with faster rates of kidney function decline. Compared to persons with pulse pressure 40–50mmHg, eGFRSCysC decline was 0.29 (p=0.006), 0.56 (p<0.001), and 0.91 (p<0.001) ml/min/1.73m2/year faster among persons with pulse pressure 50–60, 60–70, and >70mmHg, respectively. Compared to the highest quartile of SAE (most elastic), eGFRSCysC decline was 0.26 (p=0.009), 0.35 (p=0.001), and 0.70 (p<0.001) ml/min/1.73m2/year faster for the second, third and fourth quartiles respectively. For LAE, compared to the highest quartile, eGFRSCysC decline was 0.28 (p=0.004), 0.58 (p<0.001), and 0.83 (p<0.001) ml/min/1.73m2/year faster for each decreasing quartile of LAE. Findings were similar with creatinine-based eGFR. In contrast, among 2,997 adults with flow-mediated dilation and kidney function measures, flow-mediated dilation was not significantly associated with kidney function decline. For every 1-SD greater flow-mediated dilation, eGFRSCysC and eGFRSCr changed by 0.05 ml/min/1.73m2/year (p=0.3) and 0.06 ml/min/1.73m2/year (p=0.04), respectively.
Limitations
We had no direct measure of GFR, in common with nearly all large population based studies.
Conclusions
Higher pulse pressure and lower arterial elasticity, but not flow-mediated dilation, were linearly and independently associated with faster kidney function decline among persons with eGFR ≥60 ml/min/1.73m2. Future studies investigate whether treatments to lower stiffness of large and small arteries may slow the rate of kidney function loss.
doi:10.1053/j.ajkd.2011.08.015
PMCID: PMC3242889  PMID: 22000727
kidney function; arterial elasticity; chronic kidney disease; atherosclerosis
4.  Retinal arteriolar caliber and urine albumin excretion: the Multi-Ethnic Study of Atherosclerosis 
Nephrology Dialysis Transplantation  2011;26(11):3523-3528.
Background. Changes in retinal microvascular caliber, which occur prior to onset of retinopathy, may indicate presence of kidney damage.
Methods. This study examined the association between retinal arteriolar [central retinal artery equivalent (CRAE)] and venular caliber [central retinal venule equivalent (CRVE)] and presence of albuminuria (micro- or macroalbuminuria) among participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort of adults aged 45–84 years without baseline clinical cardiovascular disease. During the second MESA exam, digital fundus photography was completed in 5897 participants who provided spot urine specimens. Albuminuria was defined by spot urine albumin/creatinine ratios ≥30 mg/g. Multivariable adjusted odds of albuminuria by quintiles of CRAE and CRVE were determined using logistic regression. Analyses were repeated after stratifying by presence of type 2 diabetes.
Results. Albuminuria was noted in 11.5% (n = 675) and included 584 subjects with microalbuminuria and 91 with macroalbuminuria. A significant U-shaped pattern was seen with higher prevalence of albuminuria across quintile extremes in CRAE (15.7, 8.8 and 10.6% in CRAE Quintiles 1, 3 and 5, respectively; P <0.0001). After adjustment for covariates, both narrower CRAE [odds ratios (OR) 1.55; 95% confidence interval (CI) 1.17–2.04, Quintile 1 versus 3) and wider CRAE (OR 1.44; 95% CI 1.07–1.93, Quintile 5 versus 3) were significantly associated with albuminuria. Associations appeared substantially stronger in adults with than without type 2 diabetes but the interaction term for diabetes and CRAE on presence of albuminuria did not meet statistical significance (P = 0.3). No association was noted between CRVE quintiles and albuminuria.
Conclusions. Albuminuria is associated with narrower and wider arteriolar caliber. Future studies should determine whether variation in arteriolar caliber predicts incident albuminuria and whether associations are mediated by hypertension and diabetes. Such information could further clarify early microvascular processes in the pathogenesis of kidney disease.
doi:10.1093/ndt/gfr095
PMCID: PMC3247797  PMID: 21398363
albuminuria; diabetic retinopathy; MESA (Multi-Ethnic Study of Atherosclerosis); retinal arteriolar; retinal venular
5.  Patterns of Sodium and Potassium Excretion and Blood Pressure in the African Diaspora 
Journal of Human Hypertension  2011;26(5):315-324.
Habitual levels of dietary sodium and potassium are correlated with age-related increases in blood pressure (BP) and likely play a role in this phenomenon. Although extensive published evidence exists from randomized trials, relatively few large-scale community surveys with multiple 24-hour urine collections have been reported. We obtained three 24-hour samples on 2,704 individuals from Nigeria, Jamaica and the US to evaluate patterns of intake and within-person relationships to blood pressure. The average (±s.d.) age and weight of participants across all three sites were 39.9±8.6 years and 76.1±21.2 kg, respectively, and 55% of the total participants were females. Sodium excretion increased across the East-West gradient (e.g., 123.9±54.6, 134.1±48.8, 176.6±71.0 (±s.d.) mmol, Nigeria, Jamaica and US, respectively), while potassium was essentially unchanged (e.g., 46.3±22.9, 40.7±16.1, 44.7±16.4 (±s.d.) mmol, respectively). In multivariate analyses both sodium (positively) and potassium (negatively) were strongly correlated with blood pressure (p < 0.001); quantitatively the association was stronger, and more consistent in each site individually, for potassium. Within-population day-to-day variation was also greater for sodium than for potassium. Among each population group a significant correlation was observed between sodium and urine volume, supporting the prior finding of sodium as a determinant of fluid intake in free-living individuals. These data confirm the consistency with the possible role of dietary electrolytes as hypertension risk factors, reinforcing the relevance of potassium in these populations.
doi:10.1038/jhh.2011.39
PMCID: PMC3158967  PMID: 21593783
blood pressure; sodium excretion; potassium excretion; African Diaspora
6.  Mortality Rates Across 25-Hydroxyvitamin D (25[OH]D) Levels among Adults with and without Estimated Glomerular Filtration Rate <60 ml/min/1.73 m2: The Third National Health and Nutrition Examination Survey 
PLoS ONE  2012;7(10):e47458.
Background
Previous studies exploring the association between 25[OH]D levels and mortality in adults with and without kidney disease utilized 25[OH]D thresholds that have recently been scrutinized by the Institute of Medicine Committee to Review Dietary References Intakes for Vitamin D and Calcium.
Objective
We explored all-cause mortality rates across the spectrum of 25[OH]D levels over an eighteen-year follow-up among adults with and without an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2.
Design
The study included 1,097 U.S. adults with eGFR <60 ml/min/1.73 m2 and 14, 002 adults with eGFR ≥60 ml/min/1.73 m2. Mortality rates and rate ratios (RR) across 25[OH]D groups were calculated with Poisson regression and restricted cubic splines while adjusting for covariates.
Results
Prevalence of 25[OH]D levels <30 and <20 ng/ml among adults with eGFR <60 ml/min/1.73 m2 was 76.5% (population estimate 6.2 million) and 35.4% (population estimate 2.9 million), respectively. Among adults with eGFR ≥60 ml/min/1.73 m2, 70.5% had 25[OH]D levels <30 ng/ml (population estimate 132.2 million) while 30.3% had 25[OH]D levels <20 ng/ml (population estimate 56.8 million). Significantly higher mortality rates were noted among individuals with 25[OH]D levels <12 ng/ml compared to referent group (24 to <30 ng/ml): RR1.41 (95% CI 1.17, 1.71) among individuals with eGFR <60 ml/min/1.73 m2 and RR 1.32 (95% CI 1.13, 1.56) among individuals with eGFR ≥60 ml/min/1.73 m2 after adjustment for covariates including co-morbid conditions. Mortality rates were fairly similar across all 25[OH]D groups with levels >20 ng/ml after adjustment for all covariates.
Conclusions
Regardless of presence of eGFR <60 ml/min/1.73 m2, mortality rates across groups with 25[OH]D levels 20–40 ng/ml are similar.
doi:10.1371/journal.pone.0047458
PMCID: PMC3480387  PMID: 23112816
7.  The Effect of Including Cystatin C or Creatinine in a Cardiovascular Risk Model for Asymptomatic Individuals 
American Journal of Epidemiology  2011;174(8):949-957.
The authors studied the incremental value of adding serum cystatin C or creatinine to the Framingham risk score variables (FRSVs) for the prediction of incident cardiovascular disease (CVD) among 6,653 adults without clinical CVD utilizing the Multi-Ethnic Study of Atherosclerosis (2000–2008). CVD events included coronary heart disease, heart failure, stroke, and peripheral arterial disease. Variables were transformed to yield optimal prediction of 6-year CVD events in sex-stratified models with FRSVs alone, FRSVs + cystatin C, and FRSVs + creatinine. Risk prediction in the 3 models was assessed by using the C statistic, and net reclassification improvement was calculated. The mean ages were 61.9 and 64.6 years for individuals with and without diabetes, respectively. After 6 years of follow-up, 447 (7.2%) CVD events occurred. In the total cohort, no significant change in the C statistic was noted with FRSVs + cystatin C and FRSVs + creatinine compared with FRSVs alone, and net reclassification improvement for CVD risk was extremely small and not significant with the addition of cystatin C or creatinine to FRSVs. Similar findings were noted after stratifying by baseline presence of diabetes. In conclusion, the addition of cystatin C or serum creatinine to FRSVs does not improve CVD risk prediction among adults without clinical CVD.
doi:10.1093/aje/kwr185
PMCID: PMC3218629  PMID: 21880578
cardiovascular diseases; creatinine; cystatin C; risk model
8.  Genetic variation in APOL1 and MYH9 genes is associated with chronic kidney disease among Nigerians 
Purpose
A region of chromosome 22 which includes APOL1 and MYH9 genes was recently identified as a risk locus for non-diabetic forms of kidney disease, including idiopathic and HIV-associated focal segmental glomerular sclerosis and kidney disease clinically attributed to hypertension among African Americans. The purposes of the current study were, therefore, to examine the frequency of these variants and to determine whether they are associated with chronic kidney disease (CKD) among native Africans.
Methods
To investigate the possible evidence of association between variants in these genes and non-diabetic CKD among West Africans, we performed a case/control analysis in a sample of 166 Nigerians without history of European admixture. Our study included a total of 9 variants on APOL1 (n = 4) and MYH9 (n = 5) genes.
Results
We observed significantly strong associations with previously reported APOL1 variants rs73885319 and rs60910145, and their two-allele “G1” haplotype (P < 0.005). We did not observe significant evidence of association between non-diabetic CKD and any of the MYH9 variants or haplotypes after accounting for multiple testing in our sample.
Conclusions
In conclusion, APOL1 risk variants are associated with non-diabetic forms of CKD among Nigerians of Yoruba ethnicity. Further information on APOL1/MYH9 variants may lead to screening programs, which could lead to earlier detection and interventions for non-diabetic kidney disease.
doi:10.1007/s11255-012-0263-4
PMCID: PMC3599169  PMID: 22956460
Chronic kidney disease; APOL1; MYH9; Genetic renal disease
9.  Association of Waist Circumference and Body Mass Index With All-Cause Mortality in CKD: The REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study 
Background
Obesity management requires understanding of the mortality risks associated with different adiposity measures.
Study Design
Prospective cohort
Setting and Participants
5,805 adults with BMI ≥ 18.5 and stage 1–4 CKD defined by a spot urine albumin-creatinine ratio ≥ 30 mg/g and/or an estimated glomerular filtration rate < 60 ml/min/1.73 m2 enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study
Predictor
Body mass index (BMI) in kg/m2 categorized as 18.5–24.9, 25.0–29.9, 30.0–34.9, 35.0–39.9 and ≥ 40 kg/m2 and waist circumference categorized as < 80, 80–87.9, 88–97.9, 98–107.9, and ≥ 108 cm in women and < 94, 94–101.9, 102–111.9, 112–121.9, and ≥122 cm in men.
Outcomes
All cause mortality
Measurements
BMI and WC were measured using a standardized protocol during the home visit.
Results
A total of 686 deaths (11.8%) occurred during a median follow-up of 4 years. Compared to the referent BMI category 25–29.9 kg/m2, hazard ratios for mortality were 1.27 (95% CI, 0.96–1.69) for BMI < 25 kg/m2, and 0.84 (95% CI, 0.62–1.13), 0.81 (0.52–1.26) and 0.95 (95% CI, 0.54–1.65) for BMI categories 30–34.9, 35–39.9 and ≥ 40 kg/m2, respectively, after adjustment for covariates including waist circumference. In contrast, after adjustment for covariates including BMI, higher mortality rates were noted for all waist circumference categories compared to the referent (< 80 cm in women and < 94 cm in men) with hazard ratios 1.04 (95% CI, 0.77–1.41) for waist circumference 80–87.9 in women and 94–101.9 in men, 1.29 (95% CI, 0.92–1.81) for waist circumference 88–97.9 in women and 102–111.9 in men, 1.72 (95% CI, 1.12–2.62) for waist circumference 98–107.9 in women and 112–121.9 in men, and 2.09 (95% CI, 1.26–3.46) for waist circumference ≥ 108 in women and ≥ 122 in men.
Limitations
BMI and waist circumference measured at baseline only.
Conclusions
waist circumference should be considered in conjunction with BMI when assessing mortality risk associated with obesity in adults with CKD.
doi:10.1053/j.ajkd.2011.02.390
PMCID: PMC3144322  PMID: 21601327
Obesity; waist circumference; mortality; chronic kidney disease
10.  Retinal Arteriolar Narrowing and Subsequent Development of CKD Stage 3: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Background
Microvascular disease is a major pathogenic factor for chronic kidney disease (CKD) in persons with diabetes, but the role of microvascular disease in the development of CKD in the general population is unclear. The aim of this study is to examine whether microvascular disease precedes the development of CKD stage 3 in participants of the Multi-Ethnic Study of Atherosclerosis (MESA).
Study Design
Population-based cohort study.
Setting & Participants
MESA is a prospective cohort study of adults aged 45-84 years living in 6 US communities; 4,594 adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 when they underwent retinal photography (visit 2: in 2002-2004) were examined.
Predictor
Retinal microvascular caliber measured from fundus photographs.
Outcomes
Incident CKD stage 3 (ie, eGFR <60 mL/min/1.73 m2) at 2 subsequent follow-up examinations (visit 3 in 2004-2005, and visit 4 in 2005-2007) and an annual eGFR decrease >1 mL/min/1.73 m2 computed using the CKD Epidemiology Collaboration (CKD-EPI) equation.
Results
After a median follow-up of 4.8 years, there were 232 incident CKD stage 3 cases. Overall, retinal microvascular caliber was not associated with incident CKD stage 3. However, in race-stratified analysis, narrower arterioles in whites was associated with a higher risk of developing CKD stage 3 after adjusting for age, sex, blood pressure, diabetes, and other factors (HR, 1.78; 95% CI, 1.01-3.15; P = 0.04, lowest vs highest arteriolar caliber tertile). This association was seen even in whites without hypertension and diabetes (HR, 2.95; 95% CI, 1.10-7.98; P = 0.03). Retinal arteriolar caliber was not associated with incident CKD stage 3 in African Americans, Chinese, or Hispanics.
Limitations
Analyses were based on a single eGFR measurement, and retinal microvascular caliber and eGFR measurements were not ascertained concurrently.
Conclusion
Microvascular changes as manifest in the eye may contribute to the development of CKD stage 3 in whites.
doi:10.1053/j.ajkd.2011.02.382
PMCID: PMC3197818  PMID: 21549464
Microvascular changes; retinal microvascular caliber; chronic kidney disease
11.  Cystatin C and Albuminuria as Risk Factors for Development of CKD Stage 3: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Background
The growing burden and morbidity of chronic kidney disease (CKD) warrant effective strategies for identifying those at increased risk. We examined the association of cystatin C and albuminuria with development of CKD stage 3.
Study Design
Prospective observational study.
Setting and Participants
5,422 participants from the Multi-Ethnic Study of Atherosclerosis with estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73m2.
Predictor
Participants were categorized into four mutually exclusive groups: presence or absence of microalbuminuria (albumin-creatinine ratio >17 and > 25 µg/mg in men and women, respectively) in those with or without cystatin C ≥ 1.0 mg/L.
Outcomes and Measurements
Incident CKD stage 3 was defined as eGFR < 60 ml/min/1.73m2 at the 3rd or 4th visit and an annual decline of > 1 ml/min/1.73 m2. Poisson regression was used to evaluate incident rate ratios in unadjusted and adjusted analyses that include baseline eGFR.
Results
Mean age was 61 years, 49% were men, 38% white, 11% had diabetes, 13.7% had cystatin C ≥ 1mg/L, 8.4% had microalbuminuria, and 2.7 % had cystatin C ≥ 1 mg/L with microalbuminuria. 554 (10%) participants developed CKD stage 3 over a median follow-up of 4.7 years and the adjusted incidence rate ratios (95% CI) were 1.57 (1.19–2.07), 1.37 (1.13–1.66), and 2.12 (1.61–2.80) in those with microalbuminuria, cystatin C ≥ 1 mg/L, and both, respectively, compared to those with neither.
Limitations
Relatively short follow up and absence of measured GFR.
Conclusions
Cystatin C and microalbuminuria are independent risk factors for incident CKD stage 3 and could be useful as screening tools to identify those at increased risk.
doi:10.1053/j.ajkd.2010.11.021
PMCID: PMC3090544  PMID: 21296473
12.  Obesity and Albuminuria Among Adults With Type 2 Diabetes 
Diabetes Care  2009;32(5):851-853.
OBJECTIVE
To determine the association between obesity measures and albuminuria in adults with type 2 diabetes.
RESEARCH DESIGN AND METHODS
In the Look AHEAD (Action for Health in Diabetes) Study, BMI and waist circumference were measured among 4,985 participants while total percent body fat was measured by whole-body DEXA scans among 1,351 participants. Odds of albuminuria by quartiles of BMI, waist circumference, and percent total body fat were calculated using logistic regression analysis while adjusting for covariates.
RESULTS
The highest quartile of BMI (odds ratio [OR] 1.72 [95% CI 1.40–2.11]) and waist circumference (OR 1.75 [95% CI 1.42–2.15]) was significantly associated with albuminuria compared with the lowest quartile after adjustment for covariates. No associations were noted between quartiles of percent total body fat and albuminuria in any model.
CONCLUSIONS
Increased BMI and abdominal obesity are associated with albuminuria in overweight and obese adults with type 2 diabetes.
doi:10.2337/dc08-2059
PMCID: PMC2671132  PMID: 19196893
13.  The Association of Cell Cycle Checkpoint 2 Variants and Kidney Function: Findings of the Family Blood Pressure Program and the Atherosclerosis Risk in Communities Study 
American journal of hypertension  2009;22(5):552-558.
BACKGROUND
Recent experimental evidence suggests that DNA damage and cell cycle regulatory proteins are involved in kidney injury and apoptosis. The checkpoint 2 gene (CHEK2) is an important transducer in DNA damage signaling pathways in response to injury, and therefore, CHEK2 variants may affect susceptibility to kidney disease.
METHODS
We used tag-single-nucleotide polymorphisms (tag-SNPs) to evaluate the association of the CHEK2 with kidney function (estimated glomerular filtration rate, eGFR) in 1,549 African-American and 1,423 white Hypertension Genetic Epidemiology Network (HyperGEN) participants. We performed replication analyses in the Genetic Epidemiology Network of Arteriopathy (GENOA) participants (1,746 African Americans and 1,418 whites), GenNet participants (706 whites), and Atherosclerosis Risk in Communities (ARIC) study participants (3,783 African Americans and 10,936 whites). All analyses were race-stratified and used additive genetic models with adjustments for covariates and for family structure, if needed.
RESULTS
One tag-SNP, rs5762764, was associated with eGFR in HyperGEN P = (0.003) and GENOA white participants (P = 0.009), and it was significantly associated with eGFR in meta-analyses (P = 0.002). The associations were independent of type 2 diabetes.
CONCLUSIONS
These results suggest that CHEK2 variants may influence eGFR in the context of hypertension.
doi:10.1038/ajh.2009.41
PMCID: PMC2727134  PMID: 19265784
14.  The Differential Association of Kidney Dysfunction With Small and Large Arterial Elasticity 
American Journal of Epidemiology  2009;169(6):740-748.
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 m2): 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.
doi:10.1093/aje/kwn392
PMCID: PMC2727212  PMID: 19131564
albuminuria; cystatin C; elasticity; kidney; kidney diseases
15.  Mild elevations of urine albumin excretion are associated with atherogenic lipoprotein abnormalities in the Multi-Ethnic Study of Atherosclerosis 
Atherosclerosis  2007;197(1):407-414.
Objective
Elevated urine albumin excretion is an established risk factor for cardiovascular disease. Increased cardiovascular risk may be partly mediated by abnormalities in lipoprotein metabolism. We examined cross-sectional associations of urine albumin-creatinine ratio (ACR) with standard lipid measurements and with lipoprotein particle concentrations measured by Nuclear Magnetic Resonance (NMR) in the Multi-Ethnic Study of Atherosclerosis.
Methods and Results
Among 5633 participants who were not using lipid-lowering medications, greater ACR was associated with greater triglyceride concentration and lesser high density lipoprotein cholesterol concentration (women only), but not with low density lipoprotein (LDL) cholesterol calculated using conventional methods. In contrast, unadjusted mean small LDL particle concentrations measured by NMR were 770, 827, and 935 nmol/L for women (p<0.001) and 996, 1030, and 1040 nmol/L for men (p=0.037) among participants with normal, high normal, and elevated ACR. Adjusting for age, race/ethnicity, diabetes, impaired fasting glucose, hypertension, smoking, medications, body mass index, and serum creatinine, each two-fold greater ACR was associated with an increase in small LDL particle concentration of 27 nmol/L for women (p<0.001) and 14 nmol/L for men (p=0.008). Greater ACR was also associated with greater intermediate density lipoprotein particle concentration and smaller mean LDL particle size.
Conclusions
Mild elevations of urine ACR are associated with atherogenic lipoprotein abnormalities that are not directly observed with a standard lipid panel.
doi:10.1016/j.atherosclerosis.2007.06.018
PMCID: PMC2288670  PMID: 17681346
Albuminuria; kidney; lipids; lipoproteins; epidemiology
16.  Sugary Soda Consumption and Albuminuria: Results from the National Health and Nutrition Examination Survey, 1999–2004 
PLoS ONE  2008;3(10):e3431.
Background
End-stage renal disease rates rose following widespread introduction of high fructose corn syrup in the American diet, supporting speculation that fructose harms the kidney. Sugar-sweetened soda is a primary source of fructose. We therefore hypothesized that sugary soda consumption was associated with albuminuria, a sensitive marker for kidney disease.
Methodology/Principal Findings
Design was a cross-sectional analysis. Data were drawn from the National Health and Nutrition Examination Survey (NHANES), 1999–2004. The setting was a representative United States population sample. Participants included adults 20 years and older with no history of diabetes mellitus (n = 12,601); after exclusions for missing outcome and covariate information (n = 3,243), the analysis dataset consisted of 9,358 subjects. Exposure was consumption of two or more sugary soft drinks, based on 24-hour dietary recall. The main outcome measure was Albuminuria, defined by albumin to creatinine ratio cutpoints of >17 mg/g (males) and >25 mg/g (females). Logistic regression adjusted for confounders (diet soda, age, race-ethnicity, gender, poverty). Interactions between age, race-ethnicity, gender, and overweight-obesity were explored. Further analysis adjusted for potential mediators: energy intake, basal metabolic rate, obesity, hypertension, lipids, serum uric acid, smoking, energy expenditure, and glycohemoglobin. Alternative soda intake definitions and cola consumption were employed.
Results
Weighted albuminuria prevalence was 11%, and 17% consumed 2+ sugary soft drinks/day. The confounder-adjusted odds ratio for sugary soda was 1.40 (95% confidence interval: 1.13, 1.74). Associations were modified by gender (p = 0.008) and overweight-obesity (p = 0.014). Among women, the OR was 1.86 (95% CI: 1.37, 2.53); the OR among males was not significant. In the group with body mass under 25 kg/m2, OR = 2.15 (95% confidence interval: 1.42, 3.25). Adjustment for potential mediators and use of alternative definitions of albuminuria and soda consumption did not appreciably change results. Diet sodas were not associated with albuminuria.
Conclusions
Findings suggest that sugary soda consumption may be associated with kidney damage, although moderate consumption of 1 or fewer sodas does not appear to be harmful. Additional studies are needed to assess whether HFCS itself, overall excess intake of sugar, or unmeasured lifestyle and confounding factors are responsible.
doi:10.1371/journal.pone.0003431
PMCID: PMC2562987  PMID: 18927611
17.  Progression of kidney disease in type 2 diabetes – beyond blood pressure control: an observational study 
BMC Nephrology  2005;6:8.
Background
The risk factors for progression of chronic kidney disease (CKD) in type 2 diabetes mellitus (DM) have not been fully elucidated. Although uncontrolled blood pressure (BP) is known to be deleterious, other factors may become more important once BP is treated.
Methods
All patients seen in the outpatient clinics of our hospital between January 1993 and September 2002 with type 2 DM and clinical evidence of CKD were evaluated. Progression of kidney disease was evaluated by rate of decline of glomerular filtration rate (GFR) as estimated from the simplified MDRD formula. Variables associated with progression in univariate analyses were examined by multivariate analysis to determine the factors independently associated with kidney disease progression.
Results
343 patients (mean age 69 years; all male; 77% Caucasian) were studied. Mean BP, glycated hemoglobin, and serum cholesterol during the study period were 138/72 mmHg, 8.1%, and 4.8 mmol/L, respectively. Mean decline of GFR was 4.5 ml min-1 1.73 m2-1 yr-1 (range -14 to +32). Low initial serum albumin (p < 0.001), black race (p < 0.001), and degree of proteinuria (p = 0.002), but not blood pressure, glycated hemoglobin, or serum cholesterol, were independently associated with progression.
Conclusion
In a cohort of diabetic patients with CKD in whom mean BP was < 140/80 mmHg, the potentially remediable factors hypoalbuminemia and proteinuria but not blood pressure were independently associated with progression of kidney disease. Further understanding of the relationship between these factors and kidney disease progression may lead to beneficial therapies in such patients.
doi:10.1186/1471-2369-6-8
PMCID: PMC1180831  PMID: 15985177

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