Dataset Information

Incident Type 2 Diabetes Among Individuals With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

ABSTRACT: 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.

SUBMITTER: Jepson C

PROVIDER: S-EPMC6309655 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Incident Type 2 Diabetes Among Individuals With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

Jepson Christopher C Hsu Jesse Y JY Fischer Michael J MJ Kusek John W JW Lash James P JP Ricardo Ana C AC Schelling Jeffrey R JR Feldman Harold I HI

American journal of kidney diseases : the official journal of the National Kidney Foundation 20180901 1

<h4>Rationale & objective</h4>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.<h4>Study design</h4>Prospective cohort study.<h4>Setting & participants</h4>1,713 participants with reduced glomerular filtration rates and without diabetes at baseline, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.<h4>Pred ...[more]

PMID: 30177484

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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 & objectiveDysnatremias have been associated with an increased risk of mortality in the chronic kidney disease (CKD) population. Our objective is to identify the prevalence of and risk factors associated with dysnatremias in a CKD population and assess the association of dysnatremias with kidney failure and mortality among patients with CKD enrolled in the Chronic Renal Insufficiency Cohort Study.Study designAnalysis of prospective cohort study.Setting & participantsAdult patients aged 21-74 years with CKD from the Chronic Renal Insufficiency Cohort study.PredictorsBaseline and time-dependent hyponatremia and hypernatremia.OutcomesAll-cause mortality and kidney failure.Analytical approachBaseline characteristics were compared using χ2 tests for categorical variables, analysis of variance for age, and Kruskal-Wallis tests for laboratory variables. Cox proportional hazards models and competing risk models were used to evaluate the association between baseline sodium level and overall mortality.ResultsOf a total of 5,444 patients with CKD, 486 (9%) had hyponatremia and 53 (1%) had hypernatremia. Altogether, 1,508 patients died and 1,206 reached kidney failure. In adjusted Cox models, time-dependent dysnatremias were strongly associated with mortality for both hyponatremia (HR, 1.38; 95% CI, 1.16-1.64) and hypernatremia (HR, 1.54; 95% CI, 1.04-2.29). Factors associated with hyponatremia included female sex, diabetes, and hypertension. Regardless of age, time-dependent hypernatremia was associated with an increased risk of kidney failure (HR, 1.64; 95% CI, 1.06-2.53). Baseline and time-dependent hyponatremia were associated with an increased risk of kidney failure in patients younger than 65 (baseline hyponatremia HR, 1.30; 95% CI, 1.03-1.64 and time-dependent hyponatremia HR, 1.36; 95% CI, 1.09-1.70) but not among patients aged >65 years.LimitationsInability to establish causality and lack of generalizability to hospitalized patients.ConclusionsDysnatremias are prevalent among ambulatory CKD patients and are associated with mortality and kidney failure. Time-dependent dysnatremias were significantly associated with mortality in patients with CKD. Time-dependent hypernatremia was associated with progression to kidney failure. Baseline and time-dependent hyponatremia were associated with an increased risk of progression to kidney failure in those younger than 65 years.

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:BackgroundNon-Hispanic blacks and Hispanics with end-stage renal disease have a lower risk for death than non-Hispanic whites, but data for racial/ethnic variation in cardiovascular outcomes for non-dialysis-dependent chronic kidney disease are limited.Study designProspective cohort.Setting & participants3,785 adults with entry estimated glomerular filtration rates of 20 to 70mL/min/1.73m(2) enrolled in the CRIC (Chronic Renal Insufficiency Cohort) Study.PredictorsRace/ethnicity (non-Hispanic white, non-Hispanic black, and Hispanic).OutcomesCardiovascular outcomes (atherosclerotic events [myocardial infarction, stroke, or peripheral arterial disease] and heart failure) and a composite of each cardiovascular outcome or all-cause death.MeasurementsMultivariable Cox proportional hazards.ResultsDuring a median follow-up of 6.6 years, we observed 506 atherosclerotic events, 551 heart failure events, and 692 deaths. In regression analyses, there were no significant differences in atherosclerotic events among the 3 racial/ethnic groups. In analyses stratified by clinical site, non-Hispanic blacks had a higher risk for heart failure events (HR, 1.59; 95% CI, 1.29-1.95), which became nonsignificant after adjustment for demographic factors and baseline kidney function. In contrast, Hispanics had similar risk for heart failure events as non-Hispanic whites. In analyses stratified by clinical site, compared with non-Hispanic whites, non-Hispanic blacks were at similar risk for atherosclerotic events or death. However, after further adjustment for cardiovascular risk factors, medications, and mineral metabolism markers, non-Hispanic blacks had 17% lower risk for the outcome (HR, 0.83; 95% CI, 0.69-0.99) than non-Hispanic whites, whereas there was no significant association with Hispanic ethnicity.LimitationsHispanics were largely recruited from a single center, and the study was underpowered to evaluate the association between Hispanic ethnicity and mortality.ConclusionsThere were no significant racial/ethnic differences in adjusted risk for atherosclerotic or heart failure outcomes. Future research is needed to better explain the reduced risk for atherosclerotic events or death in non-Hispanic blacks compared with non-Hispanic whites.

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.

Project description:BACKGROUND:People with advanced chronic kidney disease are at risk for the development of end-stage renal disease (ESRD), but also many other adverse outcomes, including cardiovascular disease (CVD) events and death. Determination of risk factors that explain the variability in prognosis and timing of these adverse outcomes can aid patient counseling and medical decision making. STUDY DESIGN:Prospective research cohort. SETTING & PARTICIPANTS:1,798 participants with estimated glomerular filtration rates (eGFRs)<30mL/min/1.73m2 in the CRIC Study were followed up for a median of 5.5 years. PREDICTORS:Age, race, sex, eGFR, proteinuria, diabetes mellitus, body mass index, ejection fraction, systolic blood pressure, history of CVD, and smoking history. OUTCOMES:ESRD, CVD (congestive heart failure, stroke, myocardial infarction, and peripheral artery disease), and death. RESULTS:Baseline age of the cohort was 60 years, 46% were women, and 46% were African American. Although 52.3% of participants progressed to ESRD during follow-up, the path by which this occurred was variable. For example, predicted 1-year probabilities for a hypothetical 60-year-old white woman with eGFR of 30mL/min/1.73m2, urine protein excretion of 1.8g/d, and no diabetes or CVD (risk characteristics similar to the average participant) were 3.3%, 4.1%, and 0.3%, for first developing CVD, ESRD, and death, respectively. For a 40-year-old African American man with similar characteristics but higher systolic blood pressure, the corresponding 1-year probabilities were 2.4%, 13.2%, and 0.1%. For all participants, the development of ESRD or CVD increased the risk for subsequent mortality, with no differences by patient race or body mass index. LIMITATIONS:The CRIC population was specifically recruited for kidney disease, and the vast majority had seen a nephrologist. CONCLUSIONS:The prognosis and timing of adverse outcomes in chronic kidney disease vary by patient characteristics. These results may help guide the development of personalized approaches for managing patients with advanced CKD.

Dataset Information

Incident Type 2 Diabetes Among Individuals With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

Publications

Incident Type 2 Diabetes Among Individuals With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

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