Chronic Renal Insufficiency Cohort Research Articles

The body composition and excretory burden of lean, obese, and severely obese individuals has implications for the assessment of chronic kidney disease

Obesity could affect associations between creatinine generation, estimated body surface area, and excretory burden, with effects on chronic kidney disease assessment. We therefore examined the impact of obesity on the performances of estimated glomerular filtration rate (eGFR), the urine albumin:creatinine ratio (ACR), and excretory burden in 3611 participants of the Chronic Renal Insufficiency Cohort. Urine creatinine excretion significantly increased with body mass index (BMI) (34 and 31% greater at 40 kg/m(2) or more versus the normal of 18.5-25 kg/m(2)) in men and women, respectively, such that patients with a normal BMI and an ACR of 30 mg/g had the same 24-h albuminuria as severely obese patients with ACR 23 mg/g. The bias of eGFR (referenced to body surface area-indexed iothalamate (i-)GFR) had a U-shaped relationship to obesity in men but progressively increased in women. Nevertheless, obesity-associated body surface area increases were accompanied by a greater absolute (non-indexed) iGFR for a given eGFR, particularly in men. Two men with eGFRs of 45 ml/min per 1.73 m(2), height 1.76 m, and BMI 22 or 45 kg/m(2) had absolute iGFRs of 46 and 62 ml/min, respectively. The excretory burden, assessed as urine urea nitrogen and estimated dietary phosphorus, sodium, and potassium intakes, also increased in obesity. However, obese men had lower odds of anemia, hyperkalemia, and hyperphosphatemia. Thus, for a given ACR and eGFR, obese individuals have greater albuminuria, absolute GFR, and excretory burden. This has implications for chronic kidney disease management, screening, and research.

Healthy Lifestyle and Risk of Kidney Disease Progression, Atherosclerotic Events, and Death in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

In general populations, healthy lifestyle is associated with fewer adverse outcomes. We estimated the degree to which adherence to a healthy lifestyle decreases the risk of renal and cardiovascular events among adults with chronic kidney disease (CKD). Prospective cohort. 3,006 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. 4 lifestyle factors (regular physical activity, body mass index [BMI] of 20-<25kg/m(2), nonsmoking, and "healthy diet"), individually and in combination. CKD progression (50% decrease in estimated glomerular filtration rate or end-stage renal disease), atherosclerotic events (myocardial infarction, stroke, or peripheral arterial disease), and all-cause mortality. Multivariable-adjusted Cox proportional hazards. During a median follow-up of 4 years, we observed 726 CKD progression events, 355 atherosclerotic events, and 437 deaths. BMI≥25kg/m(2) and nonsmoking were associated with reduced risk of CKD progression (HRs of 0.75 [95% CI, 0.58-0.97] and 0.61 [95% CI, 0.45-0.82] for BMIs of 25 to<30 and≥30kg/m(2), respectively, versus 20 to<25kg/m(2); HR for nonsmoking of 0.68 [95% CI, 0.55-0.84] compared to the current smoker reference group) and reduced risk of atherosclerotic events (HRs of 0.67 [95% CI, 0.46-0.96] for BMI of 25-<30 vs 20-<25kg/m(2) and 0.55 [95% CI, 0.40-0.75] vs current smoker). Factors associated with reduced all-cause mortality were regular physical activity (HR, 0.64 [95% CI, 0.52-0.79] vs inactive), BMI≥30kg/m(2) (HR, 0.64 [95% CI, 0.43-0.96] vs 20-<25kg/m(2)), and nonsmoking (HR, 0.45 [95% CI, 0.34-0.60] vs current smoker). BMI<20kg/m(2) was associated with increased all-cause mortality risk (HR, 2.11 [95% CI, 1.13-3.93] vs 20-<25kg/m(2)). Adherence to all 4 lifestyle factors was associated with a 68% lower risk of all-cause mortality compared to adherence to no lifestyle factors (HR, 0.32; 95% CI, 0.11-0.89). Lifestyle factors were measured only once. Regular physical activity, nonsmoking, and BMI≥25kg/m(2) were associated with lower risk of adverse outcomes in this cohort of individuals with CKD.

Genome-Wide Association Studies in Nephrology: Using Known Associations for Data Checks

Prior to conducting genome-wide association studies (GWAS) of renal traits and diseases, systematic checks to ensure data integrity and analytical work flow should be conducted. Using positive controls (ie, known associations between a single-nucleotide polymorphism [SNP] and a corresponding trait) allows for identifying errors that are not apparent solely from global evaluation of summary statistics. Strong genetic control associations of chronic kidney disease (CKD), as derived from GWAS, are lacking in the non-African ancestry CKD population; thus, in this perspective, we provide examples of and considerations for using positive controls among patients with CKD. Using data from individuals with CKD who participated in the CRIC (Chronic Renal Insufficiency Cohort) Study or PediGFR (Pediatric Investigation for Genetic Factors Linked to Renal Progression) Consortium, we evaluated 2 kinds of positive control traits: traits unrelated to kidney function (bilirubin level and body height) and those related to kidney function (cystatin C and urate levels). For the former, the proportion of variance in the control trait that is explained by the control SNP is the main determinant of the strength of the observable association, irrespective of adjustment for kidney function. For the latter, adjustment for kidney function can be effective in uncovering known associations among patients with CKD. For instance, in 1,092 participants in the PediGFR Consortium, the P value for the association of cystatin C concentrations and rs911119 in the CST3 gene decreased from 2.7×10(-3) to 2.4×10(-8) upon adjustment for serum creatinine-based estimated glomerular filtration rate. In this perspective, we give recommendations for the appropriate selection of control traits and SNPs that can be used for data checks prior to conducting GWAS among patients with CKD.

Association Between Chronic Kidney Disease Progression and Cardiovascular Disease: Results from the CRIC Study

Background and Aims: There is limited information on the risk of progression of chronic kidney disease (CKD) among individuals with CVD (cardiovascular disease). We studied the association between prevalent CVD and the risk of progression of CKD among persons enrolled in a long-term observational study. Methods: A prospective cohort study of 3,939 women and men with CKD enrolled in the chronic renal insufficiency cohort (CRIC) study between June 2003 and June 2008. Prevalent cardiovascular disease (myocardial infarction/revascularization, heart failure, stroke, and peripheral vascular disease) was determined by self-report at baseline. The primary outcome was a composite of either end-stage renal disease or a 50% decline in estimated glomerular filtration rate (eGFR) from baseline. Results: One-third (1,316 of 3,939, 33.4%) of the study participants reported a history of any cardiovascular disease, and 9.6% (n = 382) a history of heart failure at baseline. After a median follow up of 6.63 years, 1,028 patients experienced the primary outcome. The composite of any CVD at baseline was not independently associated with the primary outcome (Hazard Ratio 1.04 95% CI (0.91, 1.19)). However, a history of heart failure was independently associated with a 29% higher risk of the primary outcome (Hazard Ratio 1.29 95% CI (1.06, 1.57)). The relationship between heart failure and risk of CKD progression was consistent in subgroups defined by age, race, gender, baseline eGFR, and diabetes. Neither the composite measure of any CVD or heart failure was associated with the rate of decline in eGFR. Conclusions: Self-reported heart failure was an independent risk factor for the development of the endpoint of ESRD or 50% decline in GFR in a cohort of patients with chronic kidney disease. i 2014 S. Karger AG, Basel

Urinary creatinine excretion, bioelectrical impedance analysis, and clinical outcomes in patients with CKD: the CRIC study.

Previous studies in chronic disease states have demonstrated an association between lower urinary creatinine excretion (UCr) and increased mortality, a finding presumed to reflect the effect of low muscle mass on clinical outcomes. Little is known about the relationship between UCr and other measures of body composition in terms of the ability to predict outcomes of interest. Using data from the Chronic Renal Insufficiency Cohort (CRIC), the relationship between UCr, fat free mass (FFM) as estimated by bioelectrical impedance analysis, and (in a subpopulation) whole-body dual-energy x-ray absorptiometry assessment of appendicular lean mass were characterized. The associations of UCr and FFM with mortality and ESRD were compared using Cox proportional hazards models. A total of 3604 CRIC participants (91% of the full CRIC cohort) with both a baseline UCr and FFM measurement were included; of these, 232 had contemporaneous dual-energy x-ray absorptiometry measurements. Participants were recruited between July 2003 and March 2007. UCr and FFM were modestly correlated (rho=0.50; P<0.001), while FFM and appendicular lean mass were highly correlated (rho=0.91; P<0.001). Higher urinary urea nitrogen, black race, younger age, and lower serum cystatin C level were all significantly associated with higher UCr. Over a median (interquartile range) of 4.2 (3.1-5.0) years of follow-up, 336 (9.3%) participants died and 510 (14.2%) reached ESRD. Lower UCr was associated with death and ESRD even after adjustment for FFM (adjusted hazard ratio for death per 1 SD higher level of UCr, 0.63 [95% confidence interval, 0.56 to 0.72]; adjusted hazard ratio for ESRD per 1 SD higher level of UCr, 0.70 [95% confidence interval, 0.63 to 0.75]). Among a cohort of individuals with CKD, lower UCr is associated with death and ESRD independent of FFM as assessed by bioelectrical impedance analysis.

The National Institute of Diabetes and Digestive and Kidney Diseases Central Repositories: a valuable resource for nephrology research.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repositories, part of the National Institutes of Health (NIH), are an important resource available to researchers and the general public. The Central Repositories house samples, genetic data, phenotypic data, and study documentation from >100 NIDDK-funded clinical studies, in areas such as diabetes, digestive disease, and liver disease research. The Central Repositories also have an exceptionally rich collection of studies related to kidney disease, including the Modification of Diet in Renal Disease landmark study and recent data from the Chronic Renal Insufficiency Cohort and CKD in Children Cohort studies. The data are carefully curated and linked to the samples from the study. The NIDDK is working to make the materials and data accessible to researchers. The Data Repositories continue to improve flexible online searching tools that help researchers identify the samples or data of interest, and NIDDK has created several different paths to access the data and samples, including some funding initiatives. Over the past several years, the Central Repositories have seen steadily increasing interest and use of the stored materials. NIDDK plans to make more collections available and do more outreach and education about use of the datasets to the nephrology research community in the future to enhance the value of this resource.

Relationship between macular and retinal diseases with prevalent atrial fibrillation — An analysis of the Australian Heart Eye Study

Relationship between macular and retinal diseases with prevalent atrial fibrillation — An analysis of the Australian Heart Eye Study

Urine Neutrophil Gelatinase-Associated Lipocalin and Risk of Cardiovascular Disease and Death in CKD: Results From the Chronic Renal Insufficiency Cohort (CRIC) Study

Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria). Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study. 3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m(2) enrolled from June 2003 through August2008. Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration. Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March2011. Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories). There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5ng/mL] vs lowest [≤6.9ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths. Urine NGAL was measured only once. Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths.

High-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and risk of incident heart failure in patients with CKD: the Chronic Renal Insufficiency Cohort (CRIC) Study.

High-sensitivity troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) strongly predict heart failure (HF) in the general population. However, the interpretation of levels of these biomarkers as predictors of HF is uncertain among patients with CKD. Here, we investigated whether hsTnT and NT-proBNP are associated with incident HF among patients with CKD. In a prospective cohort analysis, we studied 3483 people with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study recruited from June of 2003 to August of 2008 who were free of HF at baseline. We used Cox regression to examine the association of baseline levels of hsTnT and NT-proBNP with incident HF after adjustment for demographic factors, traditional cardiovascular risk factors, markers of kidney disease, pertinent medication use, and mineral metabolism markers. At baseline, hsTnT levels ranged from ≤5.0 to 738.7 pg/ml, and NT-proBNP levels ranged from ≤5 to 35,000 pg/ml. Compared with those who had undetectable hsTnT, participants in the highest quartile (>26.5 pg/ml) had a significantly higher rate of HF (hazard ratio, 4.77; 95% confidence interval, 2.49 to 9.14). Similarly, compared with those in the lowest NT-proBNP quintile (<47.6 pg/ml), participants in the highest quintile (>433.0 pg/ml) experienced a substantially higher rate of HF (hazard ratio, 9.57; 95% confidence interval, 4.40 to 20.83) [corrected]. In conclusion, hsTnT and NT-proBNP were strongly associated with incident HF among a diverse cohort of individuals with mild to severe CKD. Elevations in these biomarkers may indicate subclinical changes in volume and myocardial stress that subsequently contribute to clinical HF.

Prevalence of and risk factors for reduced serum bicarbonate in chronic kidney disease.

The prevalence of metabolic acidosis increases as glomerular filtration rate falls. However, most patients with stage 4 chronic kidney disease have normal serum bicarbonate concentration while some with stage 3 chronic kidney disease have low serum bicarbonate, suggesting that other factors contribute to generation of acidosis. The purpose of this study is to identify risk factors, other than reduced glomerular filtration rate, for reduced serum bicarbonate in chronic kidney disease. This is a cross-sectional analysis of baseline data from the Chronic Renal Insufficiency Cohort Study. Multivariable logistic and linear regression models were used to relate predictor variables to the odds of low serum bicarbonate (< 22 mM) compared with normal serum bicarbonate (22-30 mM) and the coefficients of Δ serum bicarbonate concentration. The prevalence of low serum bicarbonate at baseline was 17.3%. Lower estimated glomerular filtration rate had the strongest relationship with low serum bicarbonate. Factors associated with higher odds of low serum bicarbonate, independent of estimated glomerular filtration rate, were urinary albumin/creatinine ≥ 10 mg/g, smoking, anaemia, hyperkalaemia, non-diuretic use and higher serum albumin. These and younger age, higher waist circumference, and use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers associated with negative Δ serum bicarbonate in linear regression models. Several factors not typically considered to associate with reduced serum bicarbonate in chronic kidney disease were identified including albuminuria ≥ 10 mg/g, anaemia, smoking, higher serum albumin, higher waist circumference, and use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Future studies should explore the longitudinal effect of these factors on serum bicarbonate concentration.

FGF23: more a matter of the heart than of the vessels?

In 2008, Gutierrez et al. [1] were the first to demonstrate a very powerful association between FGF23 serum levels and mortality in incident dialysis patients. Meanwhile, the same relationships were confirmed in prevalent dialysis patients, in CKD patients not on dialysis and even in patients with normal renal function [2–5], and to our knowledge no published report has failed to observe FGF23 as a significant risk predictor for hard outcomes including all-cause and cardiovascular mortality or cardiovascular morbidity. Given these uniform associations, the question has arisen, whether FGF23 levels may just reflect the toxicity of phosphate overload in these patient cohorts, or whether FGF23 may harm cardiovascular tissues by intrinsic mechanisms yet to be detailed—Myles Wolf coined the term of FGF23-related ‘collateral damage’ in this context [6]. In their seminal paper in 2011, Faul et al. [7] demonstrated that intravenous and intramyocardial injections of FGF23 injections led to left ventricular hypertrophy (LVH) in rats. Moreover, they chose the classical CKD rat model of 5/6nephrectomy with the consecutive phenotype of secondary hyperparathyroidism, hyperphosphatemia and hypertension in order to show that despite no change in this ‘clinical’ phenotype the sole administration of a FGF-receptor blocker could fully prevent the development of LVH in this model. While LVH in these experimental settings was found not to be klotho-dependent, it was instead shown that the calcineurinNFAT pathway was instrumental in this cardiac FGF-receptor signalling. Several reports also focused on FGF23-associated reactivity and remodelling of the arterial vasculature. Studies in in vitro and in vivo models as well as in humans [8–11] have demonstrated that both phosphate and FGF23 blunt endothelial function. For example, Mirza et al. [11] found a significant association of FGF23 serum levels with impaired vasoreactivity and increased arterial stiffness in a community-based cohort of subjects aged above 70 (n = 967). More recently, a couple of studies evaluated the potential direct impact of FGF23 on vascular calcification processes. Jimbo et al. [12] used both intact aortic rings obtained from uraemic rats and vascular smooth muscle cells in vitro to address this question. Here, FGF23 acted synergistically on the acceleration of phosphate-induced calcification. This effect was shown to be dependent on local expression of klotho in the vessel wall and on activation of the signal transduction pathway ERK1/2. However, in another similar experimental set-up plus in a subcohort of the Chronic Renal Insufficiency Cohort (CRIC) study (n = 1501 CKD patients) no relationships between the occurrence of vascular calcifications and FGF23 levels could be confirmed [13]. This latter setting, however, did rule out intravascular klotho expression, so the question remains under which conditions arterial vessels express klotho, or whether the detection of klotho in the experiments by Jimbo et al. was immanently limited to their individual study design. Hsu et al. [14] now provide data on the association of FGF23 with relevant surrogates of vascular function in a large patient sample of the Multi-Ethnic Study of Atherosclerosis (MESA) study cohort (n = 5977 patients). The MESA study was initiated in July 2000 to investigate the prevalence, correlates and progression of subclinical cardiovascular disease in a populationbased sample of subjects aged 45–84 years, the majority of whom presented with normal renal function [15]. Readouts of vascular reactivity were large (LAE) and small artery elasticity (SAE) measured by pulse contour analysis of the radial artery, pulse pressure measured with an automated sphygmomanometer, and ankle brachial index (ABI) calculated as the ratio of the ankle and brachial systolic blood pressures. In essence, no associations with arterial stiffness, as measured by pulse pressure, LAE, SAE, or high ABI were demonstrated in this population, confirming previous results by Scialla et al. and Lindberg et al. [13, 16]. Why are these data of importance? Firstly, the MESA study presents by far the largest and best defined study cohort evaluated in this context. Secondly, multiple measures of vascular reactivity were performed which have been proven valuable as independent predictors of outcome in this MESA cohort. However, these results must still leave open the question of whether FGF23 impacts on vascular reactivity and function in patients with advanced CKD, especially because the absolute range of FGF23 in this predominantly normal population was magnitudes below those levels reached in renal failure. IN F O C U S

Higher levels of cystatin C are associated with worse cognitive function in older adults with chronic kidney disease: the chronic renal insufficiency cohort cognitive study.

To determine the association between cognition and levels of cystatin C in persons with chronic kidney disease (CKD). Prospective observational study. Chronic Renal Insufficiency Cohort Cognitive Study. Individuals with a baseline cognitive assessment completed at the same visit as serum cystatin C measurement (N=821; mean age 64.9, 50.6% male, 48.6% white). Levels of serum cystatin C were categorized into tertiles; cognitive function was assessed using six neuropsychological tests. Scores on these tests were compared across tertiles of cystatin C using linear regression and logistic regression to examine the association between cystatin C level and cognitive performance (1 standard deviation difference from the mean). After multivariable adjustment for age, race, education, and medical comorbidities in linear models, higher levels of cystatin C were associated with worse cognition on the modified Mini-Mental State Examination, Buschke Delayed Recall, Trail-Making Test Part (Trails) A and Part B, and Boston Naming (P<.05 for all). This association remained statistically significant for Buschke Delayed Recall (P=.01) and Trails A (P=.03) after additional adjustment for estimated glomerular filtration rate (eGFR). The highest tertile of cystatin C was associated with greater likelihood of poor performance on Trails A (odds ratio (OR)=2.17, 95% confidence interval (CI)=1.16-4.06), Trails B (OR=1.89, 95% CI=1.09-3.27), and Boston Naming (OR=1.85, 95% CI=1.07-3.19) than the lowest tertile after multivariate adjustment in logistic models. In individuals with CKD, higher serum cystatin C levels were associated with worse cognition and greater likelihood of poor cognitive performance on attention, executive function, and naming. Cystatin C is a marker of cognitive impairment and may be associated with cognition independent of eGFR.

Arterial stiffness, central pressures, and incident hospitalized heart failure in the chronic renal insufficiency cohort study.

Chronic kidney disease is associated with an increased risk of heart failure (HF). We aimed to evaluate the role of large artery stiffness, brachial, and central blood pressure as predictors of incident hospitalized HF in the Chronic Renal Insufficiency Cohort (CRIC), a multiethnic, multicenter prospective observational study of patients with chronic kidney disease. We studied 2602 participants who were free of HF at baseline. Carotid-femoral pulse wave velocity (CF-PWV; the gold standard index of large artery stiffness), brachial, and central pressures (estimated via radial tonometry and a generalized transfer function) were assessed at baseline. Participants were prospectively followed up to assess the development of new-onset hospitalized HF. During 3.5 years of follow-up, 154 participants had a first hospital admission for HF. CF-PWV was a significant independent predictor of incident hospitalized HF. When compared with the lowest tertile, the hazard ratios among subjects in the middle and top CF-PWV tertiles were 2.33 (95% confidence interval, 1.37-3.97; P=0.002) and 5.24 (95% confidence interval, 3.22-8.53; P<0.0001), respectively. After adjustment for multiple confounders, the hazard ratios for the middle and top CF-PWV tertiles were 1.95 (95% confidence interval, 0.92-4.13; P=0.079) and 3.01 (95% confidence interval, 1.45-6.26; P=0.003), respectively. Brachial systolic and pulse pressure were also independently associated with incident hospitalized HF, whereas central pressures were less consistently associated with this end point. The association between CF-PWV and incident HF persisted after adjustment for systolic blood pressure. Large artery stiffness is an independent predictor of incident HF in chronic kidney disease, an association with strong biological plausibility given the known effects of large artery stiffening of left ventricular pulsatile load.

Serum aldosterone and death, end-stage renal disease, and cardiovascular events in blacks and whites: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

Prior studies have demonstrated that elevated aldosterone concentrations are an independent risk factor for death in patients with cardiovascular disease. Limited studies, however, have evaluated systematically the association between serum aldosterone and adverse events in the setting of chronic kidney disease. We investigated the association between serum aldosterone and death and end-stage renal disease in 3866 participants from the Chronic Renal Insufficiency Cohort. We also evaluated the association between aldosterone and incident congestive heart failure and atherosclerotic events in participants without baseline cardiovascular disease. Cox proportional hazards models were used to evaluate independent associations between elevated aldosterone concentrations and each outcome. Interactions were hypothesized and explored between aldosterone and sex, race, and the use of loop diuretics and renin-angiotensin-aldosterone system inhibitors. During a median follow-up period of 5.4 years, 587 participants died, 743 developed end-stage renal disease, 187 developed congestive heart failure, and 177 experienced an atherosclerotic event. Aldosterone concentrations (per SD of the log-transformed aldosterone) were not an independent risk factor for death (adjusted hazard ratio, 1.00; 95% confidence interval, 0.93-1.12), end-stage renal disease (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99-1.17), or atherosclerotic events (adjusted hazard ratio, 1.04; 95% confidence interval, 0.85-1.18). Aldosterone was associated with congestive heart failure (adjusted hazard ratio, 1.21; 95% confidence interval, 1.02-1.35). Among participants with chronic kidney disease, higher aldosterone concentrations were independently associated with the development of congestive heart failure but not for death, end-stage renal disease, or atherosclerotic events. Further studies should evaluate whether mineralocorticoid receptor antagonists may reduce adverse events in individuals with chronic kidney disease because elevated cortisol levels may activate the mineralocorticoid receptor.

Erratum to: Determinants of the creatinine clearance to glomerular filtration rate ratio in patients with chronic kidney disease: a cross-sectional study

After the publication of our paper Lin et al. “Determinants of the creatinine clearance to glomerular filtration rate ratio in patients with chronic kidney disease: a cross-sectional study” BMC Nephrology 2013, 14:268, we became aware of errors in the manuscript arising from to a misunderstanding of serum creatinine calibration in the released Chronic Renal Insufficiency Cohort (CRIC) study data obtained from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Data Repository. Specifically further multiplication by 0.95 was actually not necessary to arrive at the standardized creatinine values.Here we present the revised results of the re-analyses along with revisions of the relevant tables. Mean CrCl/iGFR ratio should be 1.13 ± 0.46 instead of 1.19 ± 0.48. The main conclusion of the paper remain unchanged: “Contrary to what had been suggested by prior smaller studies, CrCl/GFR ratio does not vary with degree of proteinuria or race/ethnicity. The ratio is also closer to 1.0 than reported by several frequently cited reports in the literature.”

Retinopathy and progression of CKD: The CRIC study.

Retinal abnormalities may be associated with changes in the renal vasculature. This study assessed the association between retinopathy and progression of kidney disease in participants of the Chronic Renal Insufficiency Cohort (CRIC) study. This was a prospective study in which patients with CKD enrolled in CRIC had nonmydriatic fundus photographs of both eyes. All CRIC participants in six clinical sites in which fundus cameras were deployed were offered participation. Photographs were reviewed at a reading center. The presence and severity of retinopathy and vessel calibers were assessed using standard protocols by graders masked to clinical information. The associations of retinal features with changes in eGFR and the need for RRT (ESRD) were assessed. Retinal images and renal progression outcomes were obtained from 1852 of the 2605 participants (71.1%) approached. During follow-up (median 2.3 years), 152 participants (8.2%) developed ESRD. Presence and severity of retinopathy at baseline were strongly associated with the risk of subsequent progression to ESRD and reductions in eGFR in unadjusted analyses. For example, participants with retinopathy were 4.4 times (95% confidence interval [95% CI], 3.12 to 6.31) more likely to develop ESRD than those without retinopathy (P<0.001). However, this association was not statistically significant after adjustment for initial eGFR and 24-hour proteinuria. Venular and arteriolar diameter calibers were not associated with ESRD or eGFR decline. The results showed a nonlinear relationship between mean ratio of arteriole/vein calibers and the risk of progression to ESRD; participants within the fourth arteriole/vein ratio quartile were 3.11 times (95% CI, 1.51 to 6.40) more likely to develop ESRD than those in the first quartile (P<0.001). The presence and severity of retinopathy were not associated with ESRD and decline in eGFR after taking into account established risk factors.

Abstract P300: Cardiovascular Risk Inequality in Subjects with Chronic Kidney Disease by Age, Race and Ethnicity in the United States

Objectives: Adults with chronic kidney disease (CKD) carry an extraordinarily excess risk for cardiovascular disease (CVD). The present study aimed to test two hypotheses: (1) Non-Hispanic black (NHB) with CKD have significantly higher CVD risk profiles than non-Hispanic white (NHW). (2) This difference significantly contributes to the excess risk of CVD in NHB versus NHW. Methods: A total of 3,939 participants aged 21-74 years old in the baseline Chronic Renal Insufficiency Cohort Study, a multiethnic population-based study supported by the National Institute of Diabetes and Digestive and Kidney Diseases, were analyzed. CKD was classified using estimate glomerular filtration rate. A sum weighted CVDRisk score was developed from multiple CVD risk factors. Differences in CVDRisk score by race/ethnicity were tested using quantile regression (QR), a novel data mining approach to identify distribution of risk factors and outcomes. Results: The prevalence of CVD was 30.7 and 38.2% in NHW and NHB with CKD (p&lt;0.001). The means (SD) of CVDRisk score were 12.6 (5.7) in NHW and 14.6 (6.4) in NHB (p&lt;0.001). QR analysis indicated that NHB had significantly higher CVDRisk score in all quantile (Qs) of CVDRisk score than NHW. This race/ethnicity difference was even worse among younger NHB (aged &lt;65). An estimated 32% of the excess CVD prevalence for NHB versus NHW may be attributable to a higher CVDRisk score in those aged&lt;65 years old. Conclusion: The study highlights an excess and disproportionate distribution of CVD risk factor profile in subjects with CKD for NHB versus NHW. An estimated one third of the excess CVD prevalence in younger NHB with CKD could be explained by their higher CVD risk factor profiles.

Abstract P188: Urinary Sodium and Potassium Excretion and Cardiovascular Diseases in Patients with Chronic Kidney Disease: the Chronic Renal Insufficiency Cohort study

Introduction: Chronic kidney disease (CKD) patients are at an increased risk of cardiovascular disease (CVD) compared to the general population. Prior studies have produced contradictory results for the associations of sodium and potassium intake with the risk of CVD. In addition, these associations have not been investigated in patients with CKD. Hypothesis: We assessed the prospective associations between urinary sodium and potassium excretion and CVD event rates among patients with CKD. Methods: The Chronic Renal Insufficiency Cohort Study (CRIC) is a prospective cohort study of 3,939 participants with CKD from seven locations in the United States. Dietary sodium and potassium intake are assessed by averaging three 24-hour urinary measures and calibrating to sex-specific mean 24-hour urinary creatinine excretion. Composite CVD event is defined as myocardial infarction (MI), stroke, or congestive heart failure (CHF). CVD events are reported every six months and confirmed by medical record adjudication. Results: Over an average 6.5 years of follow-up, 660 CVD events were observed. The highest quartile (&gt;197.7 mmol/24 hours) of adjusted sodium excretion had a hazard ratio (HR) of 1.52 (95% confidence interval 1.23, 1.88; p for trend across quartiles 70.5 mmol/24 hours) of adjusted potassium excretion had a HR of 1.46 (1.14, 1.87; p for trend across quartiles 0.0009) for composite CVD events compared to the lowest quartile (≤41.2 mmol/24 hours). When modeled continuously, every 100-mmol/24 hours higher adjusted sodium excretion was associated with an increased HR of 1.25 (1.14, 1.36) for composite CVD events, 1.25 (1.13, 1.39) for CHF, 1.32 (1.08, 1.61) for stroke, and 1.09 (0.93, 1.27) for MI. In addition, every 50-mmol/24 hour higher adjusted potassium intake was associated with an increased HR of 1.25 (1.10, 1.41) for composite CVD events, 1.32 (1.15, 1.52) for CHF, 1.11 (0.81, 1.54) for stroke, and 1.00 (0.79, 1.27) for MI. Conclusions: Our study found that high dietary sodium and potassium are both associated with an increased risk of CVD among patients with CKD. These findings suggest that reductions in high dietary sodium and potassium intake might reduce the risk of CVD among patients with CKD.

Abstract P294: Urinary Sodium and Potassium Excretion and Progression of Chronic Kidney Disease

Introduction: Chronic kidney disease is a major risk factor for end-stage renal disease, cardiovascular disease, and premature death. There are scarce data on the effects of dietary sodium and potassium intake on the development and progression of chronic kidney disease. Hypothesis: We investigated the prospective association of urinary sodium and potassium excretion with the risk of chronic kidney disease progression and all-cause mortality among patients with chronic kidney disease. Methods: The Chronic Renal Insufficiency Cohort study is a prospective, longitudinal cohort study among 3,939 patients with chronic kidney disease from 7 clinical centers in the US. Dietary sodium and potassium intake are accessed by averaging three 24-hour urinary measures and calibrating to sex-specific mean 24-hour urinary creatinine excretion. Estimated-glomerular filtration rate was obtained annually. Chronic kidney disease progression was defined as a composite end point of incident end-stage renal disease or halving of estimated-glomerular filtration rate from baseline. Results: A total of 905 events of chronic kidney disease progression and 540 deaths from all-causes were identified during follow-up. Overall, a 100-mmol/24 hours higher adjusted sodium excretion was associated with an increased hazard ratio of 1.28 (95% confidence interval 1.17, 1.41; p&lt;0.0001) for chronic kidney disease progression, 1.35 (1.21, 1.50; p&lt;0.0001) for all-cause mortality, and 1.30 (1.21, 1.41; p&lt;0.0001) for the composite outcome. Similar, a 50-mmol/24 hours higher adjusted potassium excretion was associated with increased hazard ratio of 1.56 (1.36, 1.78; p&lt;0.0001) for chronic kidney disease progression, 1.36 (1.15, 1.62; p=0.0004) for all-cause mortality, and 1.51 (1.35, 1.69; p&lt;0.0001) for the composite outcome after adjustment for important covariables, including baseline kidney function, diuretics, and other antihypertensive medication use. Conclusions: High dietary sodium and potassium intake are associated with increased risk of chronic kidney disease progression and all-cause mortality in patients with chronic kidney disease. These results suggest that a moderate reduction in dietary sodium and potassium intake might slow the progression of chronic kidney disease and reduce all-cause mortality in patients with chronic kidney disease.

Increasing Use of Vitamin D Supplementation in the Chronic Renal Insufficiency Cohort Study

This study examined rates and determinants of vitamin D supplementation among Chronic Renal Insufficiency Cohort (CRIC) participants and determined the association between dose and 25-hydroxyvitamin D (25(OH)D) level. The 2010 Institute of Medicine Report noted a significant increase in vitamin D supplementation in the general population, but use in chronic kidney disease (CKD) is unknown. CRIC is a multicenter prospective observational cohort study of 3,939 participants with a median baseline age of 60 and an estimated glomerular filtration rate (eGFR) of 42.1 mL/minute per 1.73 m2. Of the cohort, 54.9% was male, 42.1% were Black, and 48.4% were diabetic. Multivariable logistic generalized estimating equations were used to examine determinants of supplementation use assessed annually between 2003 and 2011. Cross-sectional linear regression models, based on a subset of 1,155 participants, assessed associations between supplement dose and 25(OH)D level, measured by high-performance liquid chromatography coupled with tandem mass spectrometry. The proportion of participants reporting supplement use increased (P < .0001), from 10% at baseline to 44% at 7-year follow-up visits. This was largely due to initiation of products containing only ergocalciferol or cholecalciferol. The odds of supplementation were greater in older, female, non-Black, married participants with greater education and lower body mass index. Among participants taking supplementation, dose was positively associated with 25(OH)D level, adjusted for race, season, diabetes, dietary intake, eGFR, and proteinuria. Only 3.8% of non-Black and 16.5% of Black participants taking a supplement were deficient (<20 ng/mL), whereas 22.7% of non-Black and 62.4% of black participants not reporting supplement use were deficient. Vitamin D supplementation rates rose significantly among CRIC participants over 7 years of follow-up and were associated with greater serum 25(OH)D levels. Studies of vitamin D levels on clinical outcomes in CKD and future vitamin D interventional studies should consider these changes in supplementation practices.