Chronic Renal Insufficiency Cohort Study Research Articles

Risk Factors for Total Stroke in Patients with CKD: The Chronic Renal Insufficiency Cohort Study

Risk Factors for Total Stroke in Patients with CKD: The Chronic Renal Insufficiency Cohort Study

Arterial Stiffness and Cognitive Decline in the Chronic Renal Insufficiency Cohort (CRIC) Study

Arterial Stiffness and Cognitive Decline in the Chronic Renal Insufficiency Cohort (CRIC) Study

Association of Kidney Function and Volume Overload with Incident Pulmonary Hypertension in the Chronic Renal Insufficiency Cohort (CRIC) Study

Association of Kidney Function and Volume Overload with Incident Pulmonary Hypertension in the Chronic Renal Insufficiency Cohort (CRIC) Study

Serum Magnesium and Progression of Coronary Artery Calcification: A Report from the Chronic Renal Insufficiency Cohort (CRIC) Study

Serum Magnesium and Progression of Coronary Artery Calcification: A Report from the Chronic Renal Insufficiency Cohort (CRIC) Study

Acylcarnitines and Cardiovascular Outcomes in the CKD in Children (CKiD) and Chronic Renal Insufficiency Cohort (CRIC) Studies

Acylcarnitines and Cardiovascular Outcomes in the CKD in Children (CKiD) and Chronic Renal Insufficiency Cohort (CRIC) Studies

Selection of number of clusters and warping penalty in clustering functional electrocardiogram.

Clustering functional data aims to identify unique functional patterns in the entire domain, but this can be challenging due to phase variability that distorts the observed patterns. Curve registration can be used to remove this variability, but determining the appropriate level of warping flexibility can be complicated. Curve registration also requires a target to which a functional object is aligned, typically the cross-sectional mean of functional objects within the same cluster. However, this mean is unknown prior to clustering. Furthermore, there is a trade-off between flexible warping and the number of resulting clusters. Removing more phase variability through curve registration can lead to fewer remaining variations in the functional data, resulting in a smaller number of clusters. Thus, the optimal number of clusters and warping flexibility cannot be uniquely identified. We propose to use external information to solve the identification issue. We define a cross validated Kullback-Leibler information criterion to select the number of clusters and the warping penalty. The criterion is derived from the predictive classification likelihood considering the joint distribution of both the functional data and external variable and penalizes the uncertainty in the cluster membership. We evaluate our method through simulation and apply it to electrocardiographic data collected in the Chronic Renal Insufficiency Cohort study. We identify two distinct clusters of electrocardiogram (ECG) profiles, with the second cluster exhibiting ST segment depression, an indication of cardiac ischemia, compared to the normal ECG profiles in the first cluster.

Generalized Propensity Score Methods to Assess CKD-Associated Physiologic Factors and Risk of Kidney Failure in the Chronic Renal Insufficiency Cohort (CRIC) Study.

Epidemiologic studies have identified many biochemical risk factors for chronic kidney disease (CKD) progression that are correlates of kidney function, termed here 'CKD-associated physiologic factors'. Uncertainty remains if these factors are risk factors or risk markers accounting for aspects of kidney function not otherwise captured. We aimed to use flexible machine learning, a dynamic covariate history including kidney function informative markers, and generalized propensity score (GPS) weighting, to better control confounding for such exposures. We studied 3,052 adults with CKD in the Chronic Renal Insufficiency Cohort Study. We established a 2-year run-in period and assembled 90 variables that characterize variability and trends of selected CKD-associated physiologic factors and confounders. Using SuperLearner, we created a GPS for each CKD-associated physiologic factor and performed GPS-weighted Cox regressions. For context, we also evaluated results from traditional multivariable Cox proportional hazards models as in prior studies. Similar to traditional approaches, bicarbonate, calcium, potassium, hemoglobin, and PTH were each associated with risk of kidney failure using GPS weighting. The GPS approach detected non-linear associations in many factors, some of which were not detected with traditional models. We conclude that many associations between CKD-associated physiologic factors and kidney outcomes remain strong after GPS weighting.

Association of Intake of Whole Grains with Health Outcomes in the Chronic Renal Insufficiency Cohort Study.

Patients with chronic kidney disease (CKD) are encouraged to choose refined grains instead of whole grains as part of the low-phosphorus diet for managing chronic kidney disease-mineral and bone disorders (CKD-MBD). However, there is no direct evidence indicating that limiting whole grains has a beneficial impact on CKD outcomes. This study analyzed Chronic Renal Insufficiency Cohort data in two ways, namely cross-sectional examination of CKD-MBD biomarkers and prospective examination of health outcomes. A total of 4,067 (cross-sectional) and 4,331 (prospective) participants were included. The primary exposure was reported intake of whole grains (analyzed as servings/day, servings/1,000kcal, and refined grain servings/whole grain servings). CKD-MBD biomarkers included serum phosphorus, fibroblast growth factor-23, parathyroid hormone, calcitriol, and calcium. Outcomes included cardiovascular events, kidney failure, and all-cause mortality. In adjusted models, reported intake of whole grains was associated with higher phosphorus intake and serum phosphorus when assessed crudely (serving/day), but not when analyzed in relation to energy. Higher intake of refined grain relative to whole grains was associated (all models) with higher risk of kidney failure (Model 4: 1.01, 95% CI 1.00 to 1.02; P=0.01, all-cause mortality (Model 4: 1.01, 95% CI 1.00 to 1.01; P=0.01), and cardiovasulcar disease except for the fully adjusted model. Higher dietary density was associated with lower mortality in models adjusted for demographic and clinical factors including kidney function, but not in the fully adjusted model that futher adjusted for dietary factors. Intake of whole grains was not associated with CKD-MBD biomarkers. Intake of whole grains in relation to refined grains was associated with lower risk of cardiovascular disease, kidney failure, and mortality. The results of this study put into question the long-standing practice of restricting whole grains in patients with chronic kidney disease.

Progression of Coronary Artery Calcification and Risk of Clinical Events in CKD: The Chronic Renal Insufficiency Cohort Study

Coronary artery calcification (CAC) progresses rapidly in people with chronic kidney disease (CKD) compared with the general population. We studied the association between CAC progression and higher risks of atherosclerotic cardiovascular disease (CVD), congestive heart failure, and all-cause mortality among adults with CKD. Prospective cohort study. & Participants: 1,310 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had at least one CAC scan with no prior history of CVD and with observed or imputed data on changes in CAC over time. Observed or imputed CAC progression, categorized as incident CAC among participants with zero CAC on the baseline scan, or progressive CAC when the baseline scan demonstrated CAC and there was an increase in CAC ≥50 Agatston units per year. Atherosclerotic CVD (myocardial infarction or stroke), congestive heart failure, and all-cause mortality. Cause-specific Cox proportional hazards regression, stratified by presence of CAC at baseline. A total of 545 participants without and 765 with prevalent CAC at baseline were included. During a mean 3.3 years between CAC assessments, 177 (32.5%) participants without baseline CAC developed incident CAC while 270 participants (35.3%) with baseline CAC developed a ≥50 Agatston units per year increase in CAC. After multivariable adjustment, incident CAC was associated with 2.42-fold higher rate of atherosclerotic CVD (95% confidence interval [CI]: 1.23-4.79) and 1.82-fold higher rate of all-cause mortality (95% CI: 1.03-3.22). Progressive CAC (≥50 units per year) was not associated with atherosclerotic CVD (hazard ratio [HR]: 1.42; 95% CI: 0.85-2.35) but was associated with a 1.73-fold higher rate of all-cause mortality (95% CI: 1.31-2.28). Progressive CAC was not associated with incident heart failure. Residual confounding and limited statistical power for some outcomes. Among adults with CKD stages 2-4, CAC progression over a mean 3.3 years was associated with higher risk of atherosclerotic CVD and all-cause mortality. The associations were strongest among participants without CAC at baseline.

Dietary Fiber Intake and Clinical Outcomes in Chronic Kidney Disease: A Report From the Chronic Renal Insufficiency Cohort Study

ObjectiveDietary interventions are the mainstay of chronic diseases prevention in general population, but the evidence to support such therapeutic approaches in patients with chronic kidney disease (CKD) is less robust. The objective of this study is to examine the association between dietary fiber intake and adverse cardiovascular and kidney outcomes and all-cause mortality in participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Design and MethodsA total of 3791 CRIC participants with self-reported dietary fiber intake were included in the analyses stratified by tertiles of dietary fiber at study baseline. Hazard Ratios for occurrence of all-cause mortality, composite cardiovascular events and composite kidney events were calculated using Cox Proportional Hazards models adjusted for demographic, clinical, and laboratory characteristics, including levels of inflammatory markers, C-reactive protein (CRP) and Interleukin-6 (IL-6). ResultsMean daily dietary fiber intake was 15.2 g/d. During a median (SD) follow up of 14.6 (4.4) years, 1074 deaths from any cause occurred. In multivariable adjusted models, participants in the middle and low dietary fiber tertiles had a 19% (HR [95%CI]), 1.19 [1.02, 1.39]) and 11% (1.11 [0.95, 1.31]) greater risk of death respectively, compared to those in the highest fiber intake tertile. No statistical significant associations were observed between dietary fiber intake and adverse cardiovascular and kidney outcomes. Higher dietary fiber intake was not significantly associated with lower levels of CRP and IL-6. ConclusionA lower intake of dietary fiber was not associated with all-cause mortality in participants with CKD after adjustments for kidney function and inflammatory biomarkers. There was no significant association between dietary fiber intake and adverse kidney and cardiovascular outcomes. Future randomized intervention trials are needed to identify whether a high dietary fiber intake translates into improved clinical outcomes in CKD.

Cardiovascular and Kidney Outcomes of Non-Diabetic CKD by Albuminuria Severity: Findings From the CRIC Study

The clinical trajectory of normoalbuminuric chronic kidney disease (CKD), particularly in the absence of diabetes, has not yet been well-studied. This study evaluated the association of kidney and cardiovascular outcomes with levels of albuminuria in a cohort of patients with nondiabetic CKD. Prospective cohort study. 1,463 adults with nondiabetic CKD without known glomerulonephritis and diagnosed with hypertensive nephrosclerosis or unknown cause of CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) Study. Albuminuria stage at study entry. Primary outcome: Composite kidney (halving of estimated glomerular filtration rate [eGFR], kidney transplantation, or dialysis), Secondary outcomes: (1) eGFR slope, (2) composite cardiovascular disease events (hospitalization for heart failure, myocardial infarction, stroke, or all-cause death), (3) all-cause death. Linear mixed effects and Cox proportional hazards regression analyses. Lower levels of albuminuria were associated with female sex and older age. For the primary outcome, compared with normoalbuminuria, those with moderate and severe albuminuria had higher rates of kidney outcomes (adjusted hazard ratio [AHR], 3.3 [95% CI, 2.4-4.6], and AHR, 8.6 [95% CI, 6.0-12.0], respectively) and cardiovascular outcomes (AHR, 1.5 [95% CI, 1.2-1.9], and AHR, 1.5 [95% CI, 1.1-2.0], respectively). Those with normoalbuminuria (<30μg/mg; n=863) had a slower decline in eGFR (-0.46mL/min/1.73m2 per year) compared with those with moderate (30-300μg/mg, n=372; 1.41mL/min/1.73m2 per year) or severe albuminuria (>300μg/mg, n=274; 2.63mL/min/1.73m2 per year). In adjusted analyses, kidney outcomes occurred, on average, sooner among those with moderate (8.6 years) and severe (7.3 years) albuminuria compared with those with normoalbuminuria (9.3 years) whereas the average times to cardiovascular outcomes were similar across albuminuria groups (8.2, 8.1, and 8.6 years, respectively). Self-report of CKD etiology without confirmatory kidney biopsies; residual confounding. Participants with normoalbuminuric nondiabetic CKD experienced substantially slower CKD progression but only modestly lower cardiovascular risk than those with high levels of albuminuria. These findings inform the design of future studies investigating interventions among individuals with lower levels of albuminuria. Diabetes and hypertension are the leading causes of chronic kidney disease (CKD). Urine albumin levels are associated with cardiovascular and kidney disease outcomes among individuals with CKD. However, previous studies of long-term clinical outcomes in CKD largely included patients with diabetes. As well, few studies have evaluated long-term outcomes across different levels of urine albumin among people without diabetes. In this study, we found individuals with nondiabetic CKD and low urine albumin had much slower decline of kidney function but only a modestly lower risk of a cardiovascular events compared with those with high levels of urine albumin. Individuals with low urine albumin were much more likely to have a cardiovascular event than progression of their kidney disease. These findings inform the design of future studies investigating treatments among individuals with lower levels of albuminuria.

Matrix Metalloproteinase-2 and CKD Progression: The Chronic Renal Insufficiency Cohort (CRIC) Study

Matrix 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. In 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). CRIC is a multicenter prospective cohort of adults with CKD. MMP-2 measured in plasma at baseline and at year2. A composite kidney endpoint (KRT/eGFR halving). Weighted Cox proportional hazards models for case-cohort participants. Participants were followed for a median of 4.6 years from year 2 and 6.9 years from the baseline. Persistently elevated MMP-2 (≥300ng/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<2.5g/dL at study entry. Heterogeneity of effect was found with proteinuria, with a baseline MMP-2 level of≥300ng/mL associated with an increased risk of the composite kidney endpoint (HR, 1.30; 95% CI, 1.09-1.54) only with proteinuria≥442mg/g. The observational study design limits causal interpretation. Elevated 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.

Comparative CKD risk prediction using homocitrulline and carbamylated albumin: two circulating markers of protein carbamylation

BackgroundProtein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies.MethodsBoth serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2–4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker.ResultsParticipant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35–2.66) for C-Alb, and 1.89 [1.27–2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10–1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707–0.743] with C-Alb and 0.725 [0.707–0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics.ConclusionsC-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.

A Thorough Literature Review of the Potential Benefits and Drawbacks of Long-Term Aspirin Use for the Primary Prevention of Cardiovascular Disease.

This article examines the role of aspirin in the primary prevention of cardiovascular disease. It highlights findings from major studies such as ASPREE (ASPirin in Reducing Events in the Elderly), ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events), and ASPREE-XT (ASPirin in Reducing Events in the Elderly - eXTension) , among others. The review focuses on aspirin's role in primary prevention for specific populations including older adults, diabetics, hypertension patients, rheumatoid arthritis patients, kidney transplant recipients, and those with specific lipoprotein(a) genotypes, among other groups. We review these studies, noting aspirin's role in reducing events such as myocardial infarctions and its potential for increasing bleeding risks. The review also considers the implications for patients with kidney disease, referencing the Chronic Renal Insufficiency Cohort (CRIC) study and the International Polycap Study-3 (TIPS-3) trial. Additionally, it addresses the shifting paradigms in guidelines from the US Preventive Services Task Force and other entities, underscoring the importance of individualized aspirin use by balancing benefits against bleeding risks. The article further explores the concept of platelet reactivity, discusses strategies for improving adherence to aspirin therapy, and identifies existing research gaps, such as the phenomenon of aspirin resistance. It concludes by suggesting potential areas for future investigation to enhance understanding and application of aspirin in cardiovascular disease prevention.

#1559 Using nephrology clinic data to emulate cohorts: a comparison between an electronic health records service and Chronic Renal Insufficiency Cohort

Abstract Background and Aims The amount of data contributed to evidence-synthesis is inequitably distributed among various countries in a way that most of the data is emerged from developed and/or upper middle and high income countries. One efficient and low-cost solution can be the implementation of scattered electronic health records (EHR) sources in those countries into emulated cohort studies. We aim to compare the characteristics of a custom-built nephrology clinic electronic health records (CBNC-EHR) service that is in practice for more than 13 years with Chronic Renal Insufficiency Cohort (CRIC) study which has approximately the same span and enrollment to find out about the feasibility, strengths, and challenges of the proposition. Method We compared measured variables of baseline characteristics and follow-up strategy of CRIC study with the data provided by CBNC-EHR to estimate if the care-centered database is capable of emulating a cohort study. Results Among variables of socioeconomic information at CRIC study, CBNC-EHR provides 33% at full, 33% are “partially available or easily accessible” (PAEA), and 33% are not available. 71% of variables of medical history are fully available for all patients, while only 14% are PAEA, and 14% are not available. For kidney function measures, CBNC-EHR provides 55% of variables completely, while the remaining 45% are PAEA. Obviously, no blood or urine sample were collected during ambulatory care, and no questionnaire on different aspects of health were used to gather supplementary data, contrary to CRIC study. Compared to follow-up strategy of CRIC study, which indicated Annual visits and laboratory tests and 6-month telephone follow-ups, CBNC-EHR yields data only upon personally-decided attention of patients for follow-up care, which varies widely from one patient to another. Nevertheless, the majority of patients have at least one office visit in a year, accompanied by relevant laboratory tests. CBNC-EHR provides a complete list of risk factors and comorbidities of each patient, which makes it suitable for subgrouping, as was designed in CRIC study regard the diabetes status of patients. CBNC-EHR currently has data of 6481 individuals with renal failure, compared to 3000 enrollment goal of CRIC study. However, much higher rates of dropout (estimated to be approximately 20%) and utilization of inclusion and exclusion criteria will contribute to the actual available cases to emulate a cohort study. Conclusion Implementing a care-centered database into emulation of a cohort study, is challenging and complicated. Lack of consistency, high dropout rates, imperfect baseline and complementary information, and need for extensive data cleaning are all difficulties. However, contribution to equitability of data share in evidence-synthesis, extremely lower cost of conduction, and less heterogeneity are strengths of this procedure which can have a remarkable effect on transforming medical data from less-developed countries (which understandably prioritize healthcare to research due to scarcity of resources) to effective research studies. In this paper, we compared a renowned nephrology cohort with a private nephrology clinic EHR in a developing country and showed virtual availability of data to emulate a cohort study based on the care-centered database.

#373 Risk factors for progressive cardiorenal syndrome in patients with chronic kidney disease: the CRIC study

Abstract Background and Aims Cardiorenal syndrome (CRS) is associated with poor outcomes. However, risk factors for progressive CRS are not well studied in patients with chronic kidney disease (CKD). We studied the incidence and risk factors for progressive CRS in a cohort of CKD patients. Method 3 557 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study were included in this analysis after excluding those with heart failure (HF) at baseline visits. The mean follow-up time was 10.5 years. Progressive CRS was defined as development of both HF and renal failure (RF) (dialysis or transplant) within 12 months of each other. Cox proportional hazards models were used to examine the association of risk factors with progressive CRS. In a sensitivity analysis, risk factors for CRS type 2 (HF preceded RF during entire follow up) and CRS type 4 (RF preceded HF) were analyzed. Results The average baseline age was 59 years for those with progressive CRS and 57 years for those without. The age-adjusted incidence of progressive CRS was 4.5/1000 person-years and was 5.0/1000 person-years in Men and 5.9 in Black. The multivariable-adjusted hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for traditional risk factors are as follow: less than high school education (1.82, 1.2-2.73), history of cardiovascular disease (CVD) (1.48, 1.03-2.12), lower educational attainment (per 1 standard deviation [SD]) in eGFR (1.83, 1.40-2.39), and higher (per 1 SD) albumin-to-creatinine ratio (ACR) (2.26, 1.78-2.86). The multivariable-adjusted HRs with corresponding 95% CIs for a one-standard deviation increase in novel risk factors are as follows: hemoglobin (0.82, 0.68-0.99), hemoglobin A1C (1.31, 1.14-1.52), log alkaline phosphatase (1.18, 1.00-1.38), and log brain natriuretic peptide (1.32, 1.10-1.57), adjusting for age, sex, race, clinic sites, and all significant traditional risk factors (education, CVD, eGFR, and ACR). In sensitivity analysis, the risk factor associated with both CRS type 2 and 4 were kidney dysfunction, albuminuria, and mineral bone disorder (higher alkaline phosphatase and FGF23), inflammation (TNF-α), and fibrotic factor (GDF-15), while diabetes, CVD, systolic blood pressure, waist circumference, anemia, HbA1c, and volume overload were more strongly associated with CRS type 2 compared to CRS type 4. Conclusion This study indicates that education level, history of CVD, kidney dysfunction, albuminuria, mineral bone disorder, diabetes control, anemia, volume overload, inflammation, and fibrotic factors are associated with progressive CRS. Many of these risk factors are modifiable. Further studies are warranted to assess the benefits of specific interventions to improve CRS outcomes.

#2201 Assessment of long-term cardiovascular comorbidities in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Abstract Background and Aims ANCA associated vasculitis (AAV) is closely correlated to elevated cardiovascular disease (CVD) rates, positioning it a one of the leading causes of death among these patients. The impact of AAV on the risk of CVD has not been described in large prospective cohorts with a long-term follow up. The aim of our study was to evaluate the occurrence of cardiovascular events, encompassing major adverse cardiovascular events (MACE), to delineate associated risk factors, and to draw comparisons with other cohorts of patients diagnosed with CKD. Method We included 848 patients with a diagnosis of AAV who participated in 7 EUVAS RCTs (NORAM, CYCAZAREM, CYCLOPS, MEPEX, IMPROVE, RITUXVAS, and MYCYC), recruited from 74 centers in 17 European countries. The three-point MACE outcome was defined as acute myocardial infarction (AMI), stroke, or death from cardiovascular event. We used multivariate logistic regression analysis to assess the risk factors of MACE. Patients from our cohort were compared to the patients from the Chronic Renal Insufficiency Cohort (CRIC), which is a multicenter, prospective observational cohort study of participants with CKD. Results During the median follow up of 8 years (range 0-24.5, IQR: 2.9-13.6), 100 (11.8%) patients developed diabetes, 98 (13.4%) coronary heart disease (CHD), 90 (12.1%) hypertension, 70 (9.6%) deep vein thrombosis (DVT), 43 patients (5.9%) had a stroke and 28 (3.8%) an AMI. The number of MACE during FU was 144 (17%). MACE was more frequent among patients older than 65 years (n = 62 (43.1%); p-value: 0.013). CVD was the primary cause of death in 43 patients (14%). During the first 5 years after randomization, there was a significant increase in the number of cardiovascular events compared to the period 6 years- end of follow up (CHD: n = 55 vs n = 23, p ≤ 0.001; DVT: n = 55 vs n = 29; p &amp;lt; 0.001; stroke: n = 35 vs n = 24, p-value &amp;lt; 0.001). The prognostic factors for MACE in our cohort were hemodialysis dependency during RCT, age, male sex, previous history of CHD and stroke, and occurrence of diabetes during follow up. Within the subset of patients who underwent kidney biopsy, those in the crescentic class (n = 16) followed by the mixed class (n = 15) exhibited a significant higher incidence of MACE (p = 0.02). When compared to the cohort of patients with CKD from the CRIC study, the risk for CHD was higher (13.4% (95% CI: 11.16-16.11) vs 5.4% (95% CI 4.5-6.5); respectively; RR: 2.49 (95% CI 1.91-3.24); p-value&amp;lt;0.01). Additionally, there was a higher risk for stroke (5.6% (95% CI 4.2-7.4) vs 2.8% (95% CI 2.2- 3.7); RR 1.97 (95% CI: 1.33- 2.91) p-value: 0.0006). Conclusion Patients with AAV had an increased risk of stroke and CHD compared to patients with CKD from other etiologies. During the first years after diagnosis, there is an increased risk for CVD occurrence. The prognostic factors for MACE in our cohort were hemodialysis dependency, age, male sex, previous story of CHD and stroke, and diabetes during follow up. Patients with AAV should be considered at high cardiovascular risk; therefore, the therapeutic approach should include the management of traditional cardiovascular risk factors and lifestyle modification. Efforts should be made to meet strict therapeutic targets and to implement early CVD detection programs.

Five-Year Cumulative Cardiovascular Health and Clinical Events in Patients With Chronic Kidney Disease: The CRIC Study.

Higher cardiovascular health (CVH) score is associated with lower risks of cardiovascular disease (CVD) and mortality in the general population. However, it is unclear whether cumulative CVH is associated with CVD, end-stage kidney disease (ESKD), and death in patients with chronic kidney disease. Among individuals from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we used the percentage of the maximum possible CVH score attained from baseline to the year 5 visit to calculate cumulative CVH score. Multivariable-adjusted Cox proportional hazards regression was used to investigate the associations of cumulative CVH with risks of adjudicated CVD (myocardial infarction, stroke, and heart failure), ESKD, and all-cause mortality. A total of 3939 participants (mean age, 57.7 years; 54.9% men) were included. The mean (SD) cumulative CVH score attained during 5 years was 55.5% (12.3%). Over a subsequent median 10.2-year follow-up, 597 participants developed CVD, 656 had ESKD, and 1324 died. A higher cumulative CVH score was significantly associated with lower risks of CVD, ESKD, and mortality, independent of the CVH score at year 5. Multivariable-adjusted hazard ratios and 95% CIs per 10% higher cumulative CVH score during 5 years were 0.81 (0.69-0.95) for CVD, 0.82 (0.70-0.97) for ESKD, and 0.80 (0.72-0.89) for mortality. Among patients with chronic kidney disease stages 2 to 4, a better CVH status maintained throughout 5 years is associated with lower risks of CVD, ESKD, and all-cause mortality. The findings support the need for interventions to maintain ideal CVH status for prevention of adverse outcomes in the population with chronic kidney disease.

A Bayesian Joint Model of Longitudinal Kidney Disease Progression, Recurrent Cardiovascular Events, and Terminal Event in Patients with Chronic Kidney Disease

AbstractNearly 15% (37 million) of adults in the United States (US) have chronic kidney disease (CKD). The longitudinal decline of kidney function is intricately related to the development of cardiovascular disease (CVD) and eventual “terminal” event (kidney failure and mortality) in patients with CKD. Understanding the mechanism and risk factors underlying the three key outcome processes, (1) CKD progression, (2) CVD, and (3) subsequent terminal event in the CKD patient population remains incomplete. Thus, in this work, we develop a novel trivariate joint model to study the risk factors associated with the interdependent outcomes of kidney function (as measured by longitudinal estimated glomerular filtration rate), recurrent cardiovascular events, and the terminal event. Efficient estimation and inference is proposed within a Bayesian framework using Markov Chain Monte Carlo and Bayesian P-splines for hazard functions. The proposed Bayesian framework is directly generalizable beyond trivariate outcome processes to accommodate other potential modeling of complex multi-disease processes. The method is applied to study the aforementioned trivariate processes using data from the Chronic Renal Insufficiency Cohort Study, an ongoing prospective cohort study, established by the National Institute of Diabetes and Digestive and Kidney Diseases to address the rising epidemic of CKD in the US.

Characterization of CKD illness representation profiles using patient-level factors.

Illness perceptions are the unique perspective individuals have on their illness, based on their context and experiences, and are associated with patient outcomes including coping and adherence. The purpose of this study was to explore characteristics that may be driving membership in illness perceptions cluster groups for adults with chronic kidney disease (CKD). This study was conducted within the multicenter longitudinal Chronic Renal Insufficiency Cohort (CRIC) Study. Cross-sectional data were collected and combined with CRIC data. Illness perceptions were measured using the Revised Illness Perception Questionnaire. Clustering analysis was conducted in R, and bivariate analysis including linear regression was performed in STATA 16. The sample (n = 197) had a mean age of 68, was 52% women, 53% non-White, and mean estimated glomerular filtration rate (eGFR) 56 ml/min/1.73 m2. Three cluster groups were identified, labeled as "Disengaged" (n = 20), "Well-Resourced" (n = 108), and "Distressed" (n = 69). The "Disengaged" group was characterized by low CKD knowledge, many recent hospitalization days, and the lowest perceived CKD burden. The "Well-Resourced" group was characterized by the highest levels of education, CKD knowledge, optimism, and medication adherence. The "Distressed" group was characterized by the highest levels of depression scores, comorbidity burden, CKD burden, CKD symptoms, and lowest optimism. Group membership significantly predicted the number of hospitalization days in adjusted analyses. Illness perceptions groups are associated with number of hospitalization days but are independent of many patient characteristics. Illness perceptions data could be used to tailor care for specific patients at risk for poor health outcomes.