Dataset Information

Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

ABSTRACT:

Rationale & objective

The pathogenesis of disordered mineral metabolism in chronic kidney disease (CKD) is largely informed by cross-sectional studies of humans and longitudinal animal studies. We sought to characterize the longitudinal evolution of disordered mineral metabolism during the course of CKD.

Study design

Retrospective analysis nested in a cohort study.

Setting & participants

Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had up to 5 serial annual measurements of estimated glomerular filtration rate, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), serum phosphate, and serum calcium and who subsequently reached end-stage kidney disease (ESKD) during follow-up (n = 847).

Exposure

Years before ESKD.

Outcomes

Serial FGF-23, PTH, serum phosphate, and serum calcium levels.

Analytical approach

To assess longitudinal dynamics of disordered mineral metabolism in human CKD, we used "ESKD-anchored longitudinal analyses" to express time as years before ESKD, enabling assessments of mineral metabolites spanning 8 years of CKD progression before ESKD.

Results

Mean FGF-23 levels increased markedly as time before ESKD decreased, while PTH and phosphate levels increased modestly and calcium levels declined minimally. Compared with other mineral metabolites, FGF-23 levels demonstrated the highest rate of change (velocity: first derivative of the function of concentration over time) and magnitude of acceleration (second derivative). These changes became evident approximately 5 years before ESKD and persisted without deceleration through ESKD onset. Rates of changes in PTH and phosphate levels increased modestly and without marked acceleration around the same time, with modest deceleration immediately before ESKD, when use of active vitamin D and phosphate binders increased.

Limitations

Individuals who entered the CRIC Study at early stages of CKD and who did not progress to ESKD were not studied.

Conclusions

Among patients with progressive CKD, FGF-23 levels begin to increase 5 years before ESKD and continue to rapidly accelerate until transition to ESKD.

SUBMITTER: Isakova T

PROVIDER: S-EPMC7012684 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Isakova Tamara T Cai Xuan X Lee Jungwha J Mehta Rupal R Zhang Xiaoming X Yang Wei W Nessel Lisa L Anderson Amanda Hyre AH Lo Joan J Porter Anna A Nunes Julie Wright JW Negrea Lavinia L Hamm Lee L Horwitz Edward E Chen Jing J Scialla Julia J JJ de Boer Ian H IH Leonard Mary B MB Feldman Harold I HI Wolf Myles M

American journal of kidney diseases : the official journal of the National Kidney Foundation 20191023 2

<h4>Rationale & objective</h4>The pathogenesis of disordered mineral metabolism in chronic kidney disease (CKD) is largely informed by cross-sectional studies of humans and longitudinal animal studies. We sought to characterize the longitudinal evolution of disordered mineral metabolism during the course of CKD.<h4>Study design</h4>Retrospective analysis nested in a cohort study.<h4>Setting & participants</h4>Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had up to 5 ser ...[more]

PMID: 31668375

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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:BackgroundPeople 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 designProspective research cohort.Setting & participants1,798 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.PredictorsAge, race, sex, eGFR, proteinuria, diabetes mellitus, body mass index, ejection fraction, systolic blood pressure, history of CVD, and smoking history.OutcomesESRD, CVD (congestive heart failure, stroke, myocardial infarction, and peripheral artery disease), and death.ResultsBaseline 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.LimitationsThe CRIC population was specifically recruited for kidney disease, and the vast majority had seen a nephrologist.ConclusionsThe 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.

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 & 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 & 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: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 & 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 & objectiveSocial support in older adults with chronic kidney disease (CKD) is a potentially modifiable factor that may affect important clinical outcomes such as health-related quality of life, cognitive function, and frailty. However, limited data about the effects of social support in older patients with non-dialysis-dependent CKD exist. Our objective was to evaluate the association of social support with health-related quality of life, cognitive function, and frailty in older adults with CKD.Study designCross-sectional analysis of a prospective cohort study.Setting & population1,851 participants older than 65 years with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.ExposureSocial support (Lubben Social Network Scale [LSNS]).OutcomessHealth-related quality of life (Kidney Disease Quality of Life-36), cognitive function (Modified Mini-Mental State Examination, Trail Making Test A & B, and Buschke Selective Reminder Tests), and frailty (modified Fried frailty criteria).Analytic approachMultivariable, linear, and logistic regression to determine the association between social support and health-related quality of life, cognitive function, and frailty.ResultsLow social support, defined as LSNS score < 12, was present in 22% of participants. On multivariable analysis, higher social support was associated with higher health-related quality of life (β coefficient per 1-SD increase in LSNS score; burden subscale, 2.57 (95% CI, 1.57-3.56); effects subscale, 2.21 (95% CI, 1.52-2.9); symptoms subscale, 1.64 (95% CI, 0.88-2.41); mental health composite subscale, 1.91 (95% CI, 1.40-2.43); and physical health composite score, 0.64 (95% CI, 0.03-1.24)). Higher social support was associated with better cognitive function (β coefficient per 1-SD increase in LSNS score; Modified Mini-Mental State Examination, 0.81 (95% CI, 0.44 to 1.19); Trail Making Test A & B, -2.53 (95% CI, -4.29 to -0.76) and -6.53 (95% CI, -10.07 to -2.99), respectively; Buschke Selective Reminder Test 1, 2, and 3, 0.19 (95% CI, 0.07 to 0.30); 1.59 (95% CI, 0.96 to 2.22); and 0.40 (95% CI, 0.23 to 0.56), respectively. Higher social support was associated with higher likelihood of being nonfrail (OR, 1.77; 95% CI per 1-SD higher LSNS score, 1.24-2.53).LimitationsConclusions about causality cannot be drawn from an observational cross-sectional study.ConclusionsIn older patients with CKD, higher social support was associated with higher health-related quality of life and cognitive function and less frailty.

Dataset Information

Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale & objective

Study design

Setting & participants

Exposure

Outcomes

Analytical approach

Results

Limitations

Conclusions

Publications

Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Similar Datasets

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