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Association of kidney disease outcomes with risk factors for CKD: findings from the Chronic Renal Insufficiency Cohort (CRIC) study.

ABSTRACT: Various indicators of progression of chronic kidney disease (CKD) have been used as outcomes in clinical research studies. The effect of using varying measures on the association of risk factors with CKD progression has not been well characterized.Prospective cohort study.The Chronic Renal Insufficiency Cohort (CRIC) Study (N=3,939) enrolled men and women with mild to moderate CKD, 48% of whom had diabetes and 42% were self-reported black race.Age, race, sex, diabetes, baseline estimated glomerular filtration rate (eGFR), proteinuria, and other established CKD risk factors.Death, end-stage renal disease (ESRD), and eGFR events, including: (1) eGFR halving, (2) eGFR<15mL/min/1.73m(2), (3) eGFR halving and <15mL/min/1.73m(2), (4) eGFR decrease of 20mL/min/1.73m(2), (5) eGFR halving or decrease of 20mL/min/1.73m(2), and (6) eGFR decrease of 25% and change in CKD stage.Mean entry eGFR was 44.9mL/min/1.73m(2). Annual rates of death, ESRD, and eGFR halving were 2.5%, 4.0%, and 6.1%, respectively, during an average follow-up of 5.4 years. Associations between risk factors and ESRD and eGFR events were similar across different definitions. However, these associations were substantially different from those with death. HRs for ESRD, eGFR halving, and death in the highest compared to the lowest proteinuria category were 11.83 (95% CI, 8.40-16.65), 11.19 (95% CI, 8.53-14.68), and 1.47 (95% CI, 1.10-1.96), respectively.Participants may not be representative of the entire CKD population.Using ESRD or eGFR events, but not death, in the definition of kidney disease outcomes is appropriate in follow-up studies to identify risk factors for CKD progression.

SUBMITTER: Yang W

PROVIDER: S-EPMC3946885 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Association of kidney disease outcomes with risk factors for CKD: findings from the Chronic Renal Insufficiency Cohort (CRIC) study.

Yang Wei W Xie Dawei D Anderson Amanda H AH Joffe Marshall M MM Greene Tom T Teal Valerie V Hsu Chi-yuan CY Fink Jeffrey C JC He Jiang J Lash James P JP Ojo Akinlolu A Rahman Mahboob M Nessel Lisa L Kusek John W JW Feldman Harold I HI

American journal of kidney diseases : the official journal of the National Kidney Foundation 20131030 2

<h4>Background</h4>Various indicators of progression of chronic kidney disease (CKD) have been used as outcomes in clinical research studies. The effect of using varying measures on the association of risk factors with CKD progression has not been well characterized.<h4>Study design</h4>Prospective cohort study.<h4>Setting & participants</h4>The Chronic Renal Insufficiency Cohort (CRIC) Study (N=3,939) enrolled men and women with mild to moderate CKD, 48% of whom had diabetes and 42% were self-r ...[more]

PMID: 24182662

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Project description:Non-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.Prospective cohort.3,785 adults with entry estimated glomerular filtration rates of 20 to 70mL/min/1.73m(2) enrolled in the CRIC (Chronic Renal Insufficiency Cohort) Study.Race/ethnicity (non-Hispanic white, non-Hispanic black, and Hispanic).Cardiovascular outcomes (atherosclerotic events [myocardial infarction, stroke, or peripheral arterial disease] and heart failure) and a composite of each cardiovascular outcome or all-cause death.Multivariable Cox proportional hazards.During 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.Hispanics were largely recruited from a single center, and the study was underpowered to evaluate the association between Hispanic ethnicity and mortality.There 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 & objectiveThe clinical significance of isolated diastolic hypertension in patients with chronic kidney disease (CKD) is unclear. We assessed the prevalence of isolated diastolic hypertension and its association with adverse kidney and cardiovascular outcomes in participants in the Chronic Renal Insufficiency Cohort (CRIC) study.Study designProspective cohort study.Setting & populationCRIC study participants with complete baseline data on systolic blood pressure (SBP) and diastolic BP (DBP) (N=5,621).ExposureIsolated diastolic hypertension defined as SBP ≤ 130 mm Hg and DBP >80 mm Hg.Reference groupNormotension, defined as SBP ≤ 130 mm Hg and DBP ≤ 80 mm Hg.OutcomesComposite kidney events (50% decline in estimated glomerular filtration rate or onset of kidney failure), composite cardiovascular events (myocardial infarction, heart failure, stroke, or peripheral arterial disease), and all-cause mortality.Analytical approachCox proportional hazards models adjusted for demographic, health behavior, and clinical covariates.ResultsOf the 5,621 participants, 347 (6.2%) had isolated diastolic hypertension. Among the 347 participants with isolated diastolic hypertension, there was no association between isolated diastolic hypertension and the composite kidney outcome (HR, 1.17; 95% CI, 0.93-1.47; P = 0.18), composite cardiovascular events (HR, 0.91; 95% CI, 0.65-1.27; P = 0.58), or all-cause mortality (HR, 0.82; 95% CI, 0.57-1.19; P = 0.30).LimitationsOlder age of cohort and low number of participants of Asian ethnicity limit generalizability of findings. A relatively small sample size is inadequate to detect modest associations with outcomes.ConclusionsIsolated diastolic hypertension was not associated with the risk of adverse kidney and cardiovascular events in participants with CKD.Plain language summaryClinicians frequently encounter patients with kidney disease who have controlled systolic blood pressure (BP) but high diastolic BP and do not know whether they should intensify BP treatment in an attempt to control the diastolic BP. We examined whether having controlled systolic BP but uncontrolled diastolic BP leads to worse heart and kidney outcomes in patients with chronic kidney disease. We did not find any such association. However, our study was relatively small and had a number of limitations. Till larger studies confirm or refute this finding, we recommend not increasing blood pressure medications to improve the diastolic BP control if the systolic BP is already well controlled in patients with chronic kidney disease.

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:Rationale & objectiveFew studies have investigated racial disparities in acute kidney injury (AKI), in contrast to the extensive literature on racial differences in the risk of kidney failure. We sought to study potential differences in risk in the setting of chronic kidney disease (CKD).Study designProspective cohort study.Setting & participantsWe studied 2,720 self-identified Black or White participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study from July 1, 2013, to December 31, 2017.ExposureSelf-reported race (Black vs White).OutcomeHospitalized AKI (≥50% increase from nadir to peak serum creatinine).Analytical approachCox regression models adjusting for demographics (age and sex), prehospitalization clinical risk factors (diabetes, blood pressure, cardiovascular disease, estimated glomerular filtration rate, proteinuria, receipt of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers), and socioeconomic status (insurance status and education level). In a subset of participants with genotype data, we adjusted for apolipoprotein L1 gene (APOL1) high-risk status and sickle cell trait.ResultsBlack participants (n = 1,266) were younger but had a higher burden of prehospitalization clinical risk factors. The incidence rate of first AKI hospitalization among Black participants was 6.3 (95% CI, 5.5-7.2) per 100 person-years versus 5.3 (95% CI, 4.6-6.1) per 100 person-years among White participants. In an unadjusted Cox regression model, Black participants were at a modestly increased risk of incident AKI (HR, 1.22 [95% CI, 1.01-1.48]) compared with White participants. However, this risk was attenuated and no longer significant after adjusting for prehospitalization clinical risk factors (adjusted HR, 1.02 [95% CI, 0.83-1.25]). There were only 11 AKI hospitalizations among individuals with high-risk APOL1 risk status and 14 AKI hospitalizations among individuals with sickle cell trait.LimitationsParticipants were limited to research volunteers and potentially not fully representative of all CKD patients.ConclusionsIn this multicenter prospective cohort of CKD patients, racial disparities in AKI incidence were modest and were explained by differences in prehospitalization clinical risk factors.

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 & objectiveLow serum magnesium level has been shown to be associated with increased mortality, but its role as a predictor of cardiovascular disease is unclear. This study evaluates the association between serum magnesium level and cardiovascular events and all-cause mortality in a large cohort of individuals with chronic kidney disease (CKD).Study designProspective cohort study.Setting & participants3,867 participants with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.ExposuresSerum magnesium measured at study baseline.OutcomesComposite cardiovascular events (myocardial infarction, cerebrovascular accident, heart failure, and peripheral arterial disease) and all-cause mortality.Analytical approachCox proportional hazards models adjusted for demographic, clinical, and laboratory characteristics.ResultsDuring the 14.6 (4.4) years (standard deviation) of follow-up, 1,384 participants died (36/1,000 person-years), and 1,227 (40/1,000 person-years) had a composite cardiovascular event. There was a nonlinear association between serum magnesium level and all-cause mortality. Low and high magnesium levels were associated with greater rates of all-cause mortality after adjusting for demographics, comorbid conditions, medications including diuretics, estimated glomerular filtration rate, and proteinuria (P < 0.001). No significant associations were observed between serum magnesium levels and the composite cardiovascular events. Low serum magnesium level was associated with incident atrial fibrillation (HR, 1.36; 95% CI, 1.01-1.82; P = 0.04).LimitationsSingle measurement of serum magnesium.ConclusionsIn this large CKD cohort, serum magnesium level < 1.9 mg/dL and >2.1 mg/dL was associated with increased risk for all-cause mortality. Low magnesium level was associated with incident atrial fibrillation but not with composite cardiovascular disease events. Further studies are needed to determine the optimal range of serum magnesium in CKD to prevent adverse clinical outcomes.

Project description:Rationale & objectiveThere are limited data about the prevalence and prognostic significance of orthostatic hypo- and hypertension in patients with chronic kidney disease. The objective of this study is to determine the prevalence of orthostatic hypo- and hypertension in a cohort of patients with chronic kidney disease and examine their association with clinical outcomes.Study designProspective cohort study: Chronic Renal Insufficiency Cohort (CRIC) Study.Setting & population7 clinical centers, participants with chronic kidney disease.ExposuresOrthostatic hypotension (decline in systolic blood pressure [BP] > 20 mm Hg) and orthostatic hypertension (increase in systolic BP > 20 mm Hg) from seated to standing position.OutcomesCardiovascular and kidney outcomes and mortality.Analytical approachLogistic regression was used to determine factors associated with orthostatic hypo- and hypertension; Cox regression was used to examine associations with clinical outcomes.ResultsMean age of study population (n = 3,873) was 58.1 ± 11.0 years. There was a wide distribution of change in systolic BP from seated to standing (from -73.3 to +60.0 mm Hg); 180 participants (4.6%) had orthostatic hypotension and 81 (2.1%) had orthostatic hypertension. Diabetes, reduced body mass index, and β-blocker use were independently associated with orthostatic hypotension. Black race and higher body mass index were independently associated with orthostatic hypertension. After a median follow-up of 7.9 years, orthostatic hypotension was independently associated with high risk for cardiovascular (HR, 1.12; 95% CI, 1.03-1.21) but not kidney outcomes or mortality. Orthostatic hypertension was independently associated with high risk for kidney (HR, 1.51; 96% CI, 1.14-1.97) but not cardiovascular outcomes or mortality.LimitationsOrthostatic change in BP was ascertained at a single visit.ConclusionsOrthostatic hypotension was independently associated with higher risk for cardiovascular outcomes, whereas orthostatic hypertension was associated with higher risk for kidney outcomes. These findings highlight the importance of orthostatic BP measurement in practice and the need for future investigation to understand the mechanisms and potential interventions to minimize the risk associated with orthostatic changes in BP.

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: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 & objectiveSafe analgesic choices are limited in chronic kidney disease (CKD). We conducted a comparative analysis of harm from opioids versus nonsteroidal anti-inflammatory drugs (NSAIDs) in CKD.Study designProspective cohort study.Setting & participants3,939 patients with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study.Exposures30-day analgesic use reported at annual visits.OutcomesA composite outcome of 50% glomerular filtration rate reduction and kidney failure requiring kidney replacement therapy (KRT), as well as the outcomes of kidney failure requiring KRT, hospitalization, and pre-kidney failure death.Analytical approachMarginal structural models with time-updated exposures.ResultsParticipants were followed up for a median of 6.84 years, with 391 (9.9%) and 612 (15.5%) reporting baseline opioid and NSAID use, respectively. Time-updated opioid use was associated with the kidney disease composite outcome, kidney failure with KRT, death (HRs of 1.4 [95% CI, 1.2-1.7], 1.4 [95% CI, 1.1-1.7], and 1.5 [95% CI, 1.2-2.0], respectively), and hospitalization (rate ratio [RR], 1.7; 95% CI, 1.6-1.9) versus opioid nonusers. Similar results were found in an analysis restricted to a subcohort of participants reporting ever using other (nonopioid and non-NSAID) analgesics or tramadol. Time-updated NSAID use was associated with increased risk for the kidney disease composite (HR, 1.2; 95% CI, 1.0-1.5) and hospitalization (RR, 1.1; 95% CI, 1.0-1.3); however, these associations were not significant in the subcohort. The association of NSAID use with the kidney disease composite outcome varied by race, with a significant risk in blacks (HR, 1.3; 95% CI, 1.0-1.7). NSAID use was associated with lower risk for kidney failure with KRT in women and individuals with glomerular filtration rate<45mL/min/1.73m2 (HRs of 0.63 [95% CI, 0.45-0.88] and 0.77 [95% CI, 0.59-0.99], respectively).LimitationsLimited periods of recall of analgesic use and potential confounding by indication.ConclusionsOpioid use had a stronger association with adverse events than NSAIDs, with the latter's association with kidney disease outcomes limited to specific subgroups, notably those of black race.

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Association of kidney disease outcomes with risk factors for CKD: findings from the Chronic Renal Insufficiency Cohort (CRIC) study.

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Association of kidney disease outcomes with risk factors for CKD: findings from the Chronic Renal Insufficiency Cohort (CRIC) study.

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