Dataset Information

Chronic Renal Insufficiency Cohort Study (CRIC): Overview and Summary of Selected Findings.

ABSTRACT: The Chronic Renal Insufficiency Cohort (CRIC) Study is a United States multicenter, prospective study of racially and ethnically diverse patients with CKD. Although the original aims of the study were to identify novel predictors of CKD progression and to elucidate the risk and manifestations of cardiovascular disease among nearly 4000 individuals with CKD, the CRIC Study has evolved into a national resource for investigation of a broad spectrum of CKD-related topics. The study has produced >90 published scientific articles, promoted many young investigative careers in nephrology, and fostered international collaborations focused on understanding the global burden of CKD. The third phase of the CRIC Study will complete enrollment of 1500 additional study participants in 2015 and is designed to answer questions regarding morbidity and mortality in mild-to-moderate CKD and to assess the burden of CKD in older persons. This review highlights some of the salient findings of the CRIC Study in the areas of race and ethnicity, CKD progression, CKD and cognition, and cardiovascular disease outcomes; it also outlines the ongoing and forthcoming opportunities for the global nephrology community to enhance its understanding of CKD and related complications through the study.

SUBMITTER: Denker M

PROVIDER: S-EPMC4633788 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Chronic Renal Insufficiency Cohort Study (CRIC): Overview and Summary of Selected Findings.

Denker Matthew M Boyle Suzanne S Anderson Amanda H AH Appel Lawrence J LJ Chen Jing J Fink Jeffrey C JC Flack John J Go Alan S AS Horwitz Edward E Hsu Chi-Yuan CY Kusek John W JW Lash James P JP Navaneethan Sankar S Ojo Akinlolu O AO Rahman Mahboob M Steigerwalt Susan P SP Townsend Raymond R RR Feldman Harold I HI

Clinical journal of the American Society of Nephrology : CJASN 20150811 11

The Chronic Renal Insufficiency Cohort (CRIC) Study is a United States multicenter, prospective study of racially and ethnically diverse patients with CKD. Although the original aims of the study were to identify novel predictors of CKD progression and to elucidate the risk and manifestations of cardiovascular disease among nearly 4000 individuals with CKD, the CRIC Study has evolved into a national resource for investigation of a broad spectrum of CKD-related topics. The study has produced >90 ...[more]

PMID: 26265715

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Project description:Rationale & objectivesFew studies have investigated racial disparities in survival among dialysis patients in a manner that considers risk factors and mortality during the phase of kidney disease before maintenance dialysis. Our objective was to explore racial variations in survival among dialysis patients and relate them to racial differences in comorbid conditions and rates of death in the setting of kidney disease not yet requiring dialysis therapy.Study designRetrospective cohort study.Settings & participants3,288 black and white participants in the Chronic Renal Insufficiency Cohort (CRIC), none of whom were receiving dialysis at enrollment.ExposureRace.OutcomeMortality.Analytic approachCox proportional hazards regression was used to examine the association between race and mortality starting at: (1) time of dialysis initiation and (2) entry into the CRIC.ResultsDuring 7.1 years of median follow-up, 678 CRIC participants started dialysis. Starting from the time of dialysis initiation, blacks had lower risk for death (unadjusted HR, 0.67; 95% CI, 0.51-0.87) compared with whites. Starting from baseline CRIC enrollment, the strength of the association between some risk factors and dialysis was notably stronger for whites than blacks. For example, the HR for dialysis onset in the presence (vs absence) of heart failure at CRIC enrollment was 1.30 (95% CI, 1.01-1.68) for blacks versus 2.78 (95% CI, 1.90-4.50) for whites, suggesting differential severity of these risk factors by race. When we included deaths occurring both before and after dialysis, risk for death was higher among blacks (vs whites) starting from CRIC enrollment (HR, 1.41; 95% CI, 1.22-1.64), but this finding was attenuated in adjusted models (HR, 1.08; 95% CI, 0.91-1.28).LimitationsResidual confounding.ConclusionsThe apparent survival advantage among blacks over whites treated with dialysis may be attributed to selected transition of a subset of whites with more severe comorbid conditions onto dialysis.

Project description:RATIONALE & OBJECTIVE:Few studies have examined incident type 2 diabetes mellitus (T2DM) in chronic kidney disease (CKD). Our objective was to examine rates of and risk factors for T2DM in CKD, using several alternative measures of glycemic control. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:1,713 participants with reduced glomerular filtration rates and without diabetes at baseline, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. PREDICTORS:Measures of kidney function and damage, fasting blood glucose, hemoglobin A1c (HbA1c), HOMA-IR (homeostatic model assessment of insulin resistance), demographics, family history of diabetes mellitus (DM), smoking status, medication use, systolic blood pressure, triglyceride level, high-density lipoprotein cholesterol level, body mass index, and physical activity. OUTCOME:Incident T2DM (defined as fasting blood glucose ? 126mg/dL or prescription of insulin or oral hypoglycemic agents). ANALYTICAL APPROACH:Concordance between fasting blood glucose and HbA1c levels was assessed using ?. Cause-specific hazards modeling, treating death and end-stage kidney disease as competing events, was used to predict incident T2DM. RESULTS:Overall T2DM incidence rate was 17.81 cases/1,000 person-years. Concordance between fasting blood glucose and HbA1c levels was low (? for categorical versions of fasting blood glucose and HbA1c = 13%). Unadjusted associations of measures of kidney function and damage with incident T2DM were nonsignificant (P ? 0.4). In multivariable models, T2DM was significantly associated with fasting blood glucose level (P = 0.002) and family history of DM (P = 0.03). The adjusted association of HOMA-IR with T2DM was comparable to that of fasting blood glucose level; the association of HbA1c level was nonsignificant (P ? 0.1). Harrell's C for the models ranged from 0.62 to 0.68. LIMITATIONS:Limited number of outcome events; predictors limited to measures taken at baseline. CONCLUSIONS:The T2DM incidence rate among individuals with CKD is markedly higher than in the general population, supporting the need for greater vigilance in this population. Measures of glycemic control and family history of DM were independently associated with incident T2DM.

Project description:BackgroundCardiometabolic disease is a major cause of morbidity and mortality in persons with chronic kidney disease (CKD). Fractalkine (CX3CL1) is a potential mediator of both atherosclerosis and metabolic disease. Studies of the relationship of CX3CL1 with risk of cardiovascular disease (CVD) events and metabolic traits are lacking, particularly in the high-risk setting of CKD.Study designCross-sectional and longitudinal observational analysis.Setting & participantsAdults with CKD from 7 US sites participating in the Chronic Renal Insufficiency Cohort (CRIC) Study.PredictorQuartiles of plasma CX3CL1 levels at baseline.OutcomesBaseline estimated glomerular filtration rate from a creatinine and cystatin C-based equation, prevalent and incident CVD, diabetes, metabolic syndrome and its criteria, homeostatic model assessment of insulin resistance, hemoglobin A1c level, myocardial infarction, all-cause mortality, and the composite outcome of myocardial infarction/all-cause mortality.ResultsAmong 3,687 participants, baseline CX3CL1 levels were associated positively with several CVD risk factors and metabolic traits, lower estimated glomerular filtration rate, and higher levels of inflammatory cytokines, as well as prevalent CVD (OR, 1.09; 95% CI, 1.01-1.19; P=0.03). Higher CX3CL1 level also was associated with prevalent diabetes (OR, 1.26; 95% CI, 1.16-1.38; P<0.001) in adjusted models. During a mean follow-up of 6 years, there were 352 deaths, 176 myocardial infarctions, and 484 composite outcomes. In fully adjusted models, 1-SD higher CX3CL1 level increased the hazard for all-cause mortality (1.11; 95% CI, 1.00-1.22; P=0.02) and the composite outcome (1.09; 95% CI, 1.00-1.19; P=0.04).LimitationsStudy design did not allow evaluation of changes over time, correlation with progression of phenotypes, or determination of causality of effect.ConclusionsCirculating CX3CL1 level may contribute to both atherosclerotic CVD and diabetes in a CKD cohort. Further studies are required to establish mechanisms through which CX3CL1 affects the pathogenesis of atherosclerosis and diabetes.

Project description:Rationale & objectiveQuality of life in chronic kidney disease (CKD) is impaired by a large burden of symptoms including some that overlap with the symptoms of heart failure (HF). We studied a group of individuals with CKD to understand the patterns and trajectories of HF-type symptoms in this setting.Study designProspective cohort study.Setting & participants3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF.PredictorsSociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and electrocardiographic parameters.OutcomeTrajectory over 5.5 years of a HF-type symptom score (modified Kansas City Cardiomyopathy Questionnaire [KCCQ] Overall Summary Score with a range of 0-100 where<75 reflects clinically significant symptoms).Analytical approachLatent class mixed models were used to model trajectories. Multinomial logistic regression was used to model relationships of predictors with trajectory group membership.ResultsFive trajectories of KCCQ score were identified in the cohort of 3,044 adults, 45% of whom were female, and whose median age was 61 years. Group 1 (41.7%) had a stable high score (minimal symptoms, average score of 96); groups 2 (35.6%) and 3 (15.6%) had stable but lower scores (mild symptoms [average of 81] and clinically significant symptoms [average of 52], respectively). Group 4 (4.9%) had a substantial worsening in symptoms over time (mean 31-point decline), and group 5 (2.2%) had a substantial improvement (mean 33-point increase) in KCCQ score. A majority of group 1 was male, without diabetes or obesity, and this group had higher baseline kidney function. A majority of groups 2 and 3 had diabetes and obesity. A majority of group 4 was male and had substantial proteinuria. Group 5 had the highest proportion of baseline cardiovascular disease (CVD).LimitationsNo validation cohort available, CKD management changes in recent years may alter trajectories, and latent class models depend on the missing at random assumption.ConclusionsDistinct HF-type symptom burden trajectories were identified in the setting of CKD, corresponding to different baseline characteristics. These results highlight the diversity of HF-type symptom experiences in individuals with CKD.

Project description:Rationale & objectiveMatrix metalloproteinase 2 (MMP-2) plays an important role in the development of fibrosis, the final common pathway of chronic kidney disease (CKD). This study aimed to assess the relationship between repeated measures of MMP-2 and CKD progression in a large, diverse prospective cohort.Study designIn a prospective cohort of Chronic Renal Insufficiency Cohort (CRIC) participants (N = 3,827), MMP-2 was measured at baseline. In a case-cohort design, MMP-2 was additionally measured at year 2 in a randomly selected subcohort and cases of estimated glomerular filtration rate (eGFR) halving or kidney replacement therapy (KRT) (N = 1,439).Setting & participantsCRIC is a multicenter prospective cohort of adults with CKD.ExposureMMP-2 measured in plasma at baseline and at year 2.OutcomesA composite kidney endpoint (KRT/eGFR halving).Analytical approachWeighted Cox proportional hazards models for case-cohort participants.ResultsParticipants were followed for a median of 4.6 years from year 2 and 6.9 years from the baseline. Persistently elevated MMP-2 (≥300 ng/mL at both baseline and year 2) increased the hazard of the composite kidney endpoint (HR, 1.61; 95% CI, 1.07-2.42; P = 0.09) after adjusting for covariates. The relationship of persistently elevated MMP-2 was modified by levels of inflammation, with a 2.6 times higher rate of the composite kidney endpoint in those with high-sensitivity C-reactive protein < 2.5 g/dL at study entry. Heterogeneity of effect was found with proteinuria, with a baseline MMP-2 level of ≥300 ng/mL associated with an increased risk of the composite kidney endpoint (HR, 1.30; 95% CI, 1.09-1.54) only with proteinuria ≥ 442 mg/g.LimitationsThe observational study design limits causal interpretation.ConclusionsElevated MMP-2 is associated with CKD progression, particularly among those with low inflammation and those with proteinuria. Future investigations are warranted to confirm the reduction in risk of CKD progression among these subgroups of patients with CKD.

Project description:Rationale & objectiveIdentification of novel risk factors for chronic kidney disease (CKD) progression may inform mechanistic investigations and improve identification of high-risk subgroups. The current study aimed to characterize CKD progression across levels of numerous risk factors and identify independent risk factors for CKD progression among those with and without diabetes.Study designThe Chronic Renal Insufficiency Cohort (CRIC) Study is a prospective cohort study of adults with CKD conducted at 7 US clinical centers.Setting & participantsParticipants (N=3,379) had up to 12.3 years of follow-up; 47% had diabetes.Predictors30 risk factors for CKD progression across sociodemographic, behavioral, clinical, and biochemical domains at baseline.OutcomesStudy outcomes were estimated glomerular filtration rate (eGFR) slope and the composite of halving of eGFR or initiation of kidney replacement therapy.Analytical approachStepwise selection of independent risk factors was performed stratified by diabetes status using linear mixed-effects and Cox proportional hazards models.ResultsAmong those without and with diabetes, respectively, mean eGFR slope was-1.4±3.3 and-2.7±4.7mL/min/1.73m2 per year. Among participants with diabetes, multivariable-adjusted hazard of the composite outcome was approximately 2-fold or greater with higher levels of the inflammatory chemokine CXCL12, the cardiac marker N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the kidney injury marker urinary neutrophil gelatinase-associated lipocalin (NGAL). Among those without diabetes, low serum bicarbonate and higher high-sensitivity troponin T, NT-proBNP, and urinary NGAL levels were all significantly associated with a 1.5-fold or greater rate of the composite outcome.LimitationsThe observational study design precludes causal inference.ConclusionsStrong associations for cardiac markers, plasma CXCL12, and urinary NGAL are comparable to that of systolic blood pressure≥140mm Hg, a well-established risk factor for CKD progression. This warrants further investigation into the potential mechanisms that these markers indicate and opportunities to use them to improve risk stratification.

Dataset Information

Chronic Renal Insufficiency Cohort Study (CRIC): Overview and Summary of Selected Findings.

Publications

Chronic Renal Insufficiency Cohort Study (CRIC): Overview and Summary of Selected Findings.

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