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Quality 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 individual with CKD to understand the patterns and trajectories of HF-type symptoms in this setting.Prospective cohort study.3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF.Sociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and EKG parameters.Trajectory 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 where75 reflects clinically significant symptoms).Latent class mixed models were used to model trajectories. Multinomial logistic regression was used to model relationships of predictors with trajectory group membership.Five 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 81, and clinically significant symptoms, average 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, non-diabetic, non-obese, and 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).No validation cohort available, CKD management changes in recent years may alter trajectories, and latent class models depend on the missing at random assumption.Distinct 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.

The approved use of transcatheter aortic valve replacement (TAVR) for aortic stenosis has expanded substantially over time. However, gaps remain with respect to accurately delineating risk for poor clinical and patient-centered outcomes. Our objective was to develop prediction models for 30-day clinical and patient-centered outcomes after TAVR within a large, diverse community-based population.We identified all adults who underwent TAVR between 2013-2019 at Kaiser Permanente Northern California, an integrated healthcare delivery system, and were monitored for the following 30-day outcomes: all-cause death, improvement in quality of life, all-cause hospitalizations, all-cause emergency department (ED) visits, heart failure (HF)-related hospitalizations, and HF-related ED visits. We developed prediction models using gradient boosting machines using linked demographic, clinical and other data from the Society for Thoracic Surgeons (STS)/American College of Cardiology (ACC) TVT Registry and electronic health records. We evaluated model performance using area under the curve (AUC) for model discrimination and associated calibration plots. We also evaluated the association of individual predictors with outcomes using logistic regression for quality of life and Cox proportional hazards regression for all other outcomes.We identified 1,565 eligible patients who received TAVR. The risks of adverse 30-day post-TAVR outcomes ranged from 1.3% (HF hospitalizations) to 15.3% (all-cause ED visits). In models with the highest discrimination, discrimination was only moderate for death (AUC 0.60) and quality of life (AUC 0.62), but better for HF-related ED visits (AUC 0.76). Calibration also varied for different outcomes. Importantly, STS risk score only independently predicted death and all-cause hospitalization but no other outcomes. Older age also only independently predicted HF-related ED visits, and race/ethnicity was not significantly associated with any outcomes.Despite using a combination of detailed STS/ACC TVT Registry and electronic health record data, predicting short-term clinical and patient-centered outcomes after TAVR remains challenging. More work is needed to identify more accurate predictors for post-TAVR outcomes to support personalized clinical decision making and monitoring strategies.

Venous thromboembolism (VTE) is commonly treated with oral anticoagulants, including warfarin or direct oral anticoagulants (DOACs). Although DOACs are associated with favorable treatment satisfaction, few studies have assessed whether quality of life differs between DOAC and warfarin users.We invited adults enrolled in two California-based integrated health care delivery systems and with a history of VTE between January 1, 2015 and June 30, 2018 to complete a survey on their experience with anticoagulants. Health-related quality of life (QOL) was assessed using the RAND 36-item Short Form Health Survey (SF-36), which measures QOL in 2 general component scores (physical and mental). We used multivariable linear regression to compare mean QOL component scores between DOAC-users and warfarin-users, adjusting for patient and clinical characteristics.Overall, 2230 patients (43.1 % women and 31.8 %75 years of age) taking anticoagulants answered at least 1 question on the SF-36, 975 taking DOACs and 1255 taking warfarin. After adjustment for patient-level factors, there were no significant differences in either physical component scores (39.2 v 38.3, p = 0.24) or mental component scores (48.5 v 49.0, p = 0.42) between DOAC and warfarin users.Health-related QOL did not significantly differ between DOAC and warfarin users with a history of VTE.

To examine the association between multimorbidity burden and incident heart failure (HF) among people with HIV (PWH) and people without HIV (PWoH).The HIV-HEART study is a retrospective cohort study that included adult PWH and PWoH aged 21 years or older at Kaiser Permanente between 2000 and 2016. Multimorbidity burden was defined by the baseline prevalence of 22 chronic conditions and was categorized as 0-1, 2-3, and 4 or more comorbidities on the basis of distribution of the overall population. People with HIV and PWoH were followed for a first HF event, all-cause death, or up to the end of follow-up on December 31, 2016. Using Cox proportional hazard regression, hazard ratios and 95% CIs were calculated to examine the association between multimorbidity burden and incident HF among PWH and PWoH, separately.The prevalences of 0-1, 2-3, and 4 or more comorbidities were 83.3%, 13.0%, and 3.7% in PWH (n=38,868), and 82.2%, 14.3%, and 3.5% in PWoH (n=386,586), respectively. After multivariable adjustment, compared with people with 0-1 comorbidities, the hazard ratios of incident HF associated with 2-3 and 4 or more comorbidities were 1.33 (95% CI, 1.04-1.71) and 2.41 (95% CI, 1.78-3.25) in PWH and 2.10 (95% CI, 1.92-2.29) and 4.09 (95% CI, 3.64-4.61) in PWoH, respectively.Multimorbidity was associated with a higher risk of incident HF among PWH and PWoH, with more prominent associations in PWoH and certain patient subgroups. The identification of specific multimorbidity patterns that contribute to higher HF risk in PWH may lead to future preventative strategies.

Heart failure (HF) is common in chronic kidney disease (CKD); identifying patients with CKD at high risk for HF may guide clinical care. We assessed the prognostic value of cardiac biomarkers and echocardiographic variables for 10-year HF prediction compared with a published clinical HF prediction equation in a cohort of participants with CKD.We studied 2147 Chronic Renal Insufficiency Cohort (CRIC) participants without prior HF with complete clinical, cardiac biomarker (N-terminal brain natriuretic peptide [NT-proBNP] and high sensitivity troponin-T [hsTnT]), and echocardiographic data (left ventricular mass [LVM] and left ventricular ejection fraction [LVEF] data). We compared the discrimination of the 11-variable Atherosclerosis Risk in Communities (ARIC) HF prediction equation with LVM, LVEF, hsTnT, and NT-proBNP to predict 10-year risk of hospitalization for HF using a Fine and Gray modeling approach. We separately evaluated prediction of HF with preserved and reduced LVEF (LVEF ≥50% and 50%, respectively). We assessed discrimination with internally valid C-indices using 10-fold cross-validation.Participants' mean (SD) age was 59 (11) years, 53% were men, 43% were Black, and mean (SD) estimated glomerular filtration rate (eGFR) was 44 (16) ml/min per 1.73 mThe ARIC HF prediction model for 10-year HF risk had modest discrimination among adults with CKD. NT-proBNP and hsTnT discriminated better than the ARIC HF model and at least as well as a model with echocardiographic variables. HF clinical prediction models tailored to adults with CKD are needed. Until then, measurement of NT-proBNP and hsTnT may be a low-burden approach to predicting HF in this population, as they offer moderate discrimination.

RATIONALE & OBJECTIVE: The utility of conventional upper reference limits (URL) for N-terminal pro brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) in chronic kidney disease (CKD) remains debated. We analyzed the distribution of hsTnT and NT-proBNP in people with CKD in ambulatory settings to examine the diagnostic value of conventional URL in this population. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: We studied participants of the Chronic Renal Insufficiency Cohort with CKD and no self-reported history of cardiovascular disease (CVD). EXPOSURE: Estimated glomerular filtration rate (eGFR). OUTCOMES: NT-proBNP and hsTnT at baseline. ANALYTICAL APPROACH:. We described the proportion of participants above the conventional URL for NT-proBNP (125 pg/ml) and hsTnT (14 ng/L) overall, and by eGFR. We then estimated 99(th) percentile URL for NT-proBNP and hsTnT. Using quantile regression of the 99(th) percentile, we modeled the association of eGFR with NT-proBNP and hsTnT. RESULTS: Among 2,312 CKD participants, 40% and 43% had levels of NT-proBNP and hsTnT above conventional URL, respectively. In those with eGFR

Accurate diagnosis of arrhythmias is improved with longer monitoring duration but can risk delayed diagnosis. We compared diagnostic yield, outcomes, and resource utilization by arrhythmia monitoring strategy in 330 matched adults (mean age 64 years, 40% women, and 30% non-White) without previously documented atrial fibrillation or atrial flutter (AF/AFL) who received ambulatory electrocardiographic monitoring by 14-day Zio XT (patch-based continuous monitor), 24-hour Holter, or 30-day event monitor (external loop recorder) between October 2011 and May 2014. Patients were matched by age, gender, site, likelihood of receiving Zio XT patch, and indication for monitoring, and subsequently followed for monitoring results, management changes, clinical outcomes, and resource utilization. AF/AFL ≥30 seconds was noted in 6% receiving Zio XT versus 0% by Holter (p = 0.04) and 3% by event monitor (p = 0.07). Nonsustained ventricular tachycardia was noted in 24% for Zio XT patch versus 8% (p0.001) for Holter and 4% (p0.001) for event monitor. No significant differences between monitoring strategies in outcomes or resource utilization were observed. Prolonged monitoring with 14-day Zio XT patch or 30-day event monitor was superior to 24-hour Holter in detecting new AF/AFL but not different from each other. Documented nonsustained ventricular tachycardia was more frequent with Zio XT than 24-hour Holter and 30-day event monitor without apparent increased risk of adverse outcomes or excess utilization. In conclusion, additional efforts are needed to further personalize electrocardiographic monitoring strategies that optimize clinical management and outcomes.

Disordered iron and mineral homeostasis are interrelated complications of chronic kidney disease that may influence cardiovascular and kidney outcomes. In a prospective analysis of 3747 participants in the Chronic Renal Insufficiency Cohort Study, we investigated risks of mortality, heart failure, end-stage kidney disease (ESKD), and atherosclerotic cardiovascular disease according to iron status, and tested for mediation by C-terminal fibroblast growth factor 23 (FGF23), hemoglobin and parathyroid hormone. Study participants were agnostically categorized based on quartiles of transferrin saturation and ferritin as: “Iron Replete” (27.1% of participants; referent group for all outcomes analyses), “Iron Deficiency” (11.1%), “Functional Iron Deficiency” (7.6%), “Mixed Iron Deficiency” (iron indices between the Iron Deficiency and Functional Iron Deficiency groups; 6.3%), “High Iron” (9.2%), or “Non-Classified” (the remaining 38.8% of participants). In multivariable-adjusted Cox models, Iron Deficiency independently associated with mortality (hazard ratio 1.28, 95% confidence interval 1.04–1.58) and heart failure (1.34, 1.05–1.72). Mixed Iron Deficiency associated with mortality (1.61, 1.27–2.04) and ESKD (1.33, 1.02–1.73). High Iron associated with mortality (1.54, 1.24–1.91), heart failure (1.58, 1.21–2.05), and ESKD (1.41, 1.13–1.77). Functional Iron Deficiency did not significantly associate with any outcome, and no iron group significantly associated with atherosclerotic cardiovascular disease. Among the candidate facilitators, FGF23 most significantly mediated the risks of mortality and heart failure conferred by Iron Deficiency. Thus, alterations in iron homeostasis associated with adverse cardiovascular and kidney outcomes in patients with chronic kidney disease.

Background Limited existing data suggest that the novel COVID-19 may increase risk of VTE, but information from large, ethnically diverse populations with appropriate control participants is lacking. Research Question Does the rate of VTE among adults hospitalized with COVID-19 differ from matched hospitalized control participants without COVID-19? Study Design and Methods We conducted a retrospective study among hospitalized adults with laboratory-confirmed COVID-19 and hospitalized adults without evidence of COVID-19 matched for age, sex, race or ethnicity, acute illness severity, and month of hospitalization between January 2020 and August 2020 from two integrated health care delivery systems with 36 hospitals. Outcomes included VTE (DVT or pulmonary embolism ascertained using diagnosis codes combined with validated natural language processing algorithms applied to electronic health records) and death resulting from any cause at 30 days. Fine and Gray hazards regression was performed to evaluate the association of COVID-19 with VTE after accounting for competing risk of death and residual differences between groups, as well as to identify predictors of VTE in patients with COVID-19. Results We identified 6,319 adults with COVID-19 and 6,319 matched adults without COVID-19, with mean ± SD age of 60.0 ± 17.2 years, 46% women, 53.1% Hispanic, 14.6% Asian/Pacific Islander, and 10.3% Black. During 30-day follow-up, 313 validated cases of VTE (160 COVID-19, 153 control participants) and 1,172 deaths (817 in patients with COVID-19, 355 in control participants) occurred. Adults with COVID-19 showed a more than threefold adjusted risk of VTE (adjusted hazard ratio, 3.48; 95% CI, 2.03-5.98) compared with matched control participants. Predictors of VTE in patients with COVID-19 included age ≥ 55 years, Black race, prior VTE, diagnosed sepsis, prior moderate or severe liver disease, BMI ≥ 40 kg/m2, and platelet count > 217 k/μL. Interpretation Among ethnically diverse hospitalized adults, COVID-19 infection increased the risk of VTE, and selected patient characteristics were associated with higher thromboembolic risk in the setting of COVID-19.

Rationale & Objective Circulating cardiac biomarkers may signal potential mechanistic pathways involved in heart failure (HF) and atrial fibrillation (AF). Single measures of circulating cardiac biomarkers are strongly associated with incident HF and AF in chronic kidney disease (CKD). We tested the associations of longitudinal changes in the N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), galectin-3, growth differentiation factor 15 (GDF-15), and soluble ST-2 (sST-2) with incident HF and AF in patients with CKD. Study Design Observational, case-cohort study design. Setting & Participants Adults with CKD enrolled in the Chronic Renal Insufficiency Cohort study. Exposures Biomarkers were measured at baseline and 2 years later among those without kidney failure. We created 3 categories of absolute change in each biomarker: the lowest quartile, the middle 2 quartiles, and the top quartile. Outcomes The primary outcomes were incident HF and AF. Analytical Approach Cox proportional hazards regression models were used to test the associations of the change categories of each cardiac biomarker with each outcome (with the middle 2 quartiles of change as the referent group), adjusting for potential confounders and baseline concentrations of each biomarker. Results The incident HF analysis included 789 participants (which included 138 incident HF cases), and the incident AF analysis included 774 participants (123 incident AF cases). In multivariable models, the top quartile of NT-proBNP change (>232 pg/mL over 2 years) was associated with increased risk of incident HF (HR, 1.79 [95% CI, 1.06-3.04]) and AF (HR, 2.32 [95% CI, 1.37-3.93]) compared with the referent group. Participants in the top quartile of sST2 change (>3.37 ng/mL over 2 years) had significantly greater risk of incident HF (HR, 1.89 [95% CI, 1.13-3.16]), whereas those in the bottom quartile (≤−3.78 ng/mL over 2 years) had greater risk of incident AF (HR, 2.43 [95% CI, 1.39-4.22]) compared with the 2 middle quartiles. There was no association of changes in hsTnT, galectin-3, or GDF-15 with incident HF or AF. Limitations Observational study. Conclusions In CKD, increases in NT-proBNP were significantly associated with greater risk of incident HF and AF, and increases in sST2 were associated with HF. Further studies should investigate whether these markers of subclinical cardiovascular disease can be modified to reduce the risk of cardiovascular disease in CKD.

Introduction Management of chronic kidney disease (CKD) entails high medical complexity and often results in high hospitalization burden. There are limited data on the associations of longitudinal hospital utilization patterns with adverse clinical outcomes in individuals with CKD. Methods We derived cumulative all-cause hospitalization trajectory groups using latent class trajectory analysis in 3012 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study who were alive and did not reach end-stage kidney disease (ESKD) within 4 years of study entry. Cox proportional hazards models tested the associations between hospitalization trajectory groups and risks of ESKD and death prior to the onset of ESKD (ESKD-censored death). Results Within 4 years of study entry, there were 5658 hospitalizations among 3012 participants. We identified 3 distinct subgroups of individuals with CKD based on cumulative all-cause hospitalization trajectories over 4 years: low-utilizer (n = 1066), intermediate-utilizer (n = 1802), and high-utilizer (n = 144). High-utilizers represented a patient population of lower socioeconomic status who had a greater prevalence of comorbid conditions and lower kidney function compared with intermediate- and low-utilizers. After the 4-year ascertainment period to form the trajectory subgroups, there were 544 ESKD events and 437 ESKD-censored deaths during a median follow-up time of 5.1 years. Compared with low-utilizers, intermediate-utilizers and high-utilizers were at 1.49-fold (95% confidence interval [CI] 1.22–1.84) and 1.75-fold (95% CI 1.20–2.56) higher risk of ESKD in adjusted analyses, respectively. Compared with low-utilizers, intermediate-utilizers and high-utilizers were at 1.48-fold (95% CI 1.17–1.87) and 2.58-fold (95% CI 1.74–3.83) higher risk of ESKD-censored death in adjusted analyses, respectively. Conclusions Trajectories of cumulative all-cause hospitalization identify subgroups of individuals with CKD who are at high risk of ESKD and death., Graphical abstract

Background Multiple morbidity is the norm in advanced COPD and contributes to high symptom burden and worse outcomes. Research Question Can distinct comorbidity profiles be identified and validated in a community-based sample of patients with COPD from a large integrated health care system using a standard, commonly used diagnostic code-based comorbidity index and downstream 2-year health care use data? Study Design and Methods In this retrospective cohort study, we used latent class analysis (LCA) to identify comorbidity profiles in a population-based sample of 91,453 patients with a COPD diagnosis between 2011 and 2015. We included specific comorbid conditions from the Charlson Comorbidity Index (CCI) and accounted for variation in underlying prevalence of different comorbidities across the three study sites. Sociodemographic, clinical, and health-care use data were obtained from electronic health records (EHRs). Multivariate logistic regression analysis was used to compare rates of acute and postacute care use by class. Results The mean age was 71 ± 11 years, 55% of patients were women, 23% of patients were people of color, and 80% of patients were former or current smokers. LCA identified four distinct comorbidity profiles with progressively higher CCI scores: low morbidity (61%; 1.9 ± 1.4), metabolic renal (21%; 4.7 ± 1.8), cardiovascular (12%; 4.6 ± 1.9), and multimorbidity (7%; 7.5 ± 1.7). In multivariate models, during 2 years of follow-up, a significant, nonoverlapping increase was found in the odds of having any all-cause acute (hospitalizations, observation stays, and ED visits) and postacute care use across the comorbidity profiles. Interpretation Distinct comorbidity profiles can be identified in patients with COPD using standard EHR-based diagnostic codes, and these profiles are associated with subsequent acute and postacute care use. Population-based risk stratification schemes for end-to-end, comprehensive COPD management should consider integrating comorbidity profiles such as those found in this study.

RATIONALE & OBJECTIVE: Current dietary guidelines recommend that chronic kidney disease (CKD) patients restrict individual nutrients, such as sodium, potassium, phosphorus and protein. This approach can be difficult for patients to implement and ignores important nutrient interactions. Dietary patterns are an alternative method to intervene on diet. Our objective was to define the associations of four healthy dietary patterns with risk of CKD progression and all-cause mortality among people with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2,403 participants aged 21–74 years with an estimated glomerular filtration rate (eGFR) of 20–70 mL/min/1.73 m(2) and dietary data in the Chronic Renal Insufficiency Cohort (CRIC) study. EXPOSURES: Healthy Eating Index-2015 (HEI-2015), Alternative Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean diet (aMed), and Dietary Approaches to Stop Hypertension (DASH) diet scores were calculated from food frequency questionnaires. OUTCOMES: 1) CKD progression defined as ≥50% eGFR decline, kidney transplantation, or dialysis and 2) all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards regression models adjusted for demographic, lifestyle, and clinical covariates to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: There were 855 cases of CKD progression and 773 deaths over a maximum of 14 years. Compared with participants with the lowest adherence, the most highly adherent tertile of AHEI-2010, aMed, and DASH had lower adjusted risk of CKD progression with the strongest results for aMed (HR: 0.75, 95% CI: 0.62–0.90). Compared with participants with the lowest adherence, the highest adherence tertiles for all scores had lower adjusted risk of all-cause mortality for each index (24–31% lower risk). LIMITATIONS: Self-reported dietary intake. CONCLUSIONS: Greater adherence to several healthy dietary patterns is associated with a lower risk of CKD progression and all-cause mortality among people with CKD. Guidance to adopt healthy dietary patterns can be considered as a strategy for managing CKD. INDEX WORDS: dietary patterns, nutrition, kidney disease, renal, mortality

Introduction Cardiovascular disease (CVD) is the leading cause of mortality among individuals with chronic kidney disease (CKD). Cardiac biomarkers of myocardial distention, injury, and inflammation may signal unique pathways underlying CVD in CKD. In this analysis, we studied the association of baseline levels and changes in 4 traditional and novel cardiac biomarkers with risk of all-cause, CV, and non-CV mortality in a large cohort of patients with CKD. Methods Among 3664 adults with CKD enrolled in the Chronic Renal Insufficiency Cohort Study, we conducted a cohort study to examine the associations of baseline levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac high-sensitivity troponin T (hsTnT), growth differentiation factor−15 (GDF-15), and soluble ST-2 (sST-2) with risks of all-cause and cardiovascular (CV) mortality. Among a subcohort of 842 participants, we further examined the associations between change in biomarker levels over 2 years with risk of all-cause mortality. We used Cox proportional hazards regression models and adjusted for demographics, kidney function measures, cardiovascular risk factors, and medication use. Results After adjustment, elevated baseline levels of each cardiac biomarker were associated with increased risk of all-cause mortality: NT-proBNP (hazard ratio [HR] = 1.92, 95% confidence interval [CI] = 1.73−2.12); hsTnT (HR = 1.62, 95% CI = 1.48, 1.78]); GDF-15 (HR = 1.61, 95% CI = 1.46−1.78]); and sST-2 (HR = 1.26, CI = 1.16−1.37). Higher baseline levels of all 4 cardiac biomarkers were also associated with increased risk of CV. Declines in NT-proBNP (adjusted HR = 0.55, 95% CI = 0.36−0.86) and sST2 (HR = 0.55, 95% CI = 0.36−0.86]) over 2 years were associated with lower risk of all-cause mortality. Conclusion In a large cohort of CKD participants, elevations of NT-proBNP, hsTnT, GDF-15, and sST-2 were independently associated with greater risks of all-cause and CV mortality., Graphical abstract

Rationale & Objective Studies using a single measurement of fibroblast growth factor 23 (FGF-23) suggest that elevated FGF-23 levels are associated with increased risk for requirement for kidney replacement therapy (KRT) in patients with chronic kidney disease. However, the data do not account for changes in FGF-23 levels as kidney disease progresses. Study Design Case-cohort study. Setting & Participants To evaluate the association between serial FGF-23 levels and risk for requiring KRT, our primary analysis included 1,597 individuals in the Chronic Renal Insufficiency Cohort Study who had up to 5 annual measurements of carboxy-terminal FGF-23. There were 1,135 randomly selected individuals, of whom 266 initiated KRT, and 462 individuals who initiated KRT outside the random subcohort. Exposure Serial FGF-23 measurements and FGF-23 trajectory group membership. Outcomes Incident KRT. Analytical Approach To handle time-dependent confounding, our primary analysis of time-updated FGF-23 levels used time-varying inverse probability weighting in a discrete time failure model. To compare our results with prior data, we used baseline and time-updated FGF-23 values in weighted Cox regression models. To examine the association of FGF-23 trajectory subgroups with risk for incident KRT, we used weighted Cox models with FGF-23 trajectory groups derived from group-based trajectory modeling as the exposure. Results In our primary analysis, the HR for the KRT outcome per 1 SD increase in the mean of natural log–transformed (ln)FGF-23 in the past was 1.94 (95% CI, 1.51-2.49). In weighted Cox models using baseline and time-updated values, elevated FGF-23 level was associated with increased risk for incident KRT (HRs per 1 SD ln[FGF-23] of 1.18 [95% CI, 1.02-1.37] for baseline and 1.66 [95% CI, 1.49-1.86] for time-updated). Membership in the slowly and rapidly increasing FGF-23 trajectory groups was associated with ∼3- and ∼21-fold higher risk for incident KRT compared to membership in the stable FGF-23 trajectory group. Limitations Residual confounding and lack of intact FGF-23 values. Conclusions Increasing FGF-23 levels are independently associated with increased risk for incident KRT.

Rationale & Objectives Few 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 Design Retrospective cohort study. Settings & Participants 3,288 black and white participants in the Chronic Renal Insufficiency Cohort (CRIC), none of whom were receiving dialysis at enrollment. Exposure Race. Outcome Mortality. Analytic Approach Cox 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. Results During 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). Limitations Residual confounding. Conclusions The 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.

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.

In the general population, there is an association between higher levels of physical activity and lower risk for cardiovascular events and mortality, but this relationship has not been well evaluated in chronic kidney disease (CKD). We investigated the association between self-reported physical activity and outcomes in a CKD cohort.Prospective cohort study.3,926 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study.Time-updated self-reported physical activity assessed by (1) quartile of moderate-to-vigorous physical activity (MVPA) and (2) meeting guideline-recommended level of physical activity (categorized as active, meeting guidelines; active, not meeting guidelines; or inactive).Atherosclerotic events (myocardial infarction, stroke, or peripheral artery disease), incident heart failure, and all-cause and cardiovascular death.Cox proportional hazards regression.At baseline, compared with the lowest MVPA quartile, those in the highest quartile were more likely to be younger, male, not have prevalent cardiovascular disease, and have higher estimated glomerular filtration rate. Overall, 51% met the physical activity guidelines; of those who did not, 30% were inactive. During the median follow-up period of 13.4 years, there were 772 atherosclerotic events, 848 heart failure events, and 1,553 deaths, and 420 cardiovascular deaths. Compared with the participants in the lowest MVPA quartile, the highest quartile had a lower risk of atherosclerotic events (HR, 0.64 [95% CI, 0.51-0.79]), incident heart failure (HR, 0.71 [95% CI, 0.58-0.87]), and all-cause and cardiovascular death (HRs of 0.54 [95% CI, 0.46-0.63] and 0.47 [95% CI, 0.35-0.64], respectively). The findings were similar for analyses evaluating recommended level of physical activity.Self-reported physical activity may result in some degree of misclassification.Higher self-reported physical activity was associated with lower risk of cardiovascular events and mortality in CKD patients, which may have important implications for clinical practice and the design of interventional studies.In this long-term study of 3,926 adults with chronic kidney disease, we found that individuals with higher levels of physical activity were less likely to experience an atherosclerotic event (for example, a heart attack, stroke, or peripheral arterial disease), new-onset heart failure, and death as compared with those with lower levels of physical activity. The findings were similar for the analyses evaluating adherence to guideline-recommended level of physical activity (that is, for more than 150 minutes per week), and they strengthen the evidence supporting the current guideline recommendations.

Few 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).Prospective cohort study.We 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.Self-reported race (Black vs White).Hospitalized AKI (≥50% increase from nadir to peak serum creatinine).Cox 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.Black 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.Participants were limited to research volunteers and potentially not fully representative of all CKD patients.In this multicenter prospective cohort of CKD patients, racial disparities in AKI incidence were modest and were explained by differences in prehospitalization clinical risk factors.

Systolic blood pressure (SBP) and its association with clinical outcomes in atrial fibrillation (AF) patients in community practice are poorly characterized. In patients with AF, we sought to (1) examine the prevalence of baseline uncontrolled hypertension and the overall change in SBP control, (2) identify predictors of uncontrolled SBP over 2 years of follow-up, and (3) determine the relation between SBP and clinical outcomes. We analyzed 10,132 patients with AF at 176 clinics in the ORBIT-AF registry between 2010 and 2014, classified as: (1) no history of hypertension; (2) controlled hypertension (baseline SBP140 mm Hg); (3) and uncontrolled hypertension (baseline SBP140 mm Hg). Predictors of SBP140 mm Hg at baseline or in follow-up were identified with pooled logistic regression. Random effects Cox regression models were used to compare cardiovascular outcomes and major bleeding as a function of continuous, time-dependent SBP. Overall 8,383 (83%) of patients with AF had hypertension. Of these, 24.2% (n = 2032) had uncontrolled baseline SBP, with little change over 2 years. Predictors of elevated follow-up SBP included uncontrolled baseline SBP, females, previous percutaneous coronary intervention, and diabetes. For every 5 mm Hg increase in follow-up SBP, the adjusted risk of stroke or systemic embolism or transient ischemic attack (adjusted hazard ratio [aHR] 1.05, 95% confidence interval [CI] 1.01 to 1.08, p = 0.01), myocardial infarction (aHR 1.05, 95% CI 1.00 to 1.11, p = 0.04), and major bleeding (aHR 1.03, 95% CI 1.00 to 1.06, p = 0.04) increased modestly. In conclusion, in patients with AF, higher SBP was associated with increasing adverse events; therefore, more rigorous blood pressure control should be emphasized.

RATIONALE & OBJECTIVE: Traditional risk estimates for atherosclerotic vascular disease (ASVD) and death may not perform optimally in the setting of CKD. We sought to determine whether the addition of measures of inflammation and kidney function to traditional estimation tools improves prediction of these events in a diverse cohort of patients with CKD. STUDY DESIGN: Observational cohort study SETTING & PARTICIPANTS: 2399 Chronic Renal Insufficiency Cohort (CRIC) study participants without history of cardiovascular disease at study entry. PREDICTORS: Baseline plasma levels of biomarkers of inflammation (interleukin (IL)-1β, IL-1RA (IL-1 receptor antagonist), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor β (TGFβ), high sensitivity C-Reactive protein (hs-CRP), fibrinogen, and serum albumin), measures of kidney function (estimated glomerular filtration rate (eGFR) and albuminuria), and the Pooled Cohort Equation Probability (PCEP) estimate. OUTCOMES: Composite of ASVD events (incident myocardial infarction (MI), peripheral arterial disease (PAD), and stroke) and death. ANALYTICAL APPROACH: Cox proportional hazard models adjusted for PCEP estimates, albuminuria, and eGFR. RESULTS: During a median follow-up of 7.3 years, 86, 61, 48, and 323 participants experienced MI, PAD, stroke, or death, respectively. 1-decile greater levels of IL-6 (adjusted Hazard Ratio [aHR], 1.12; 95% CI, 1.08-1.16; p

Introduction: A cornerstone of kidney disease management is participation in guideline-recommended health behaviors. However, the relationship of these health behaviors with outcomes, and the identification of barriers to health behavior engagement, have not been described among younger and older adults with chronic kidney disease. Methods: Data from a cohort study of 5499 individuals with chronic kidney disease was used to identify health behavior patterns with latent class analysis stratified by age

Objective: The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD). Background: IPE is a highly purified and stable omega-3 fatty acid prescription medication that is approved for cardiovascular risk reduction in high-risk adults on statin therapy with elevated triglycerides. Preclinical data and clinical observations suggest that IPE may have pleiotropic effects including antiviral and anti-inflammatory properties that may prevent or reduce the downstream sequelae and cardiopulmonary consequences of viral URIs. Methods: MITIGATE is a virtual, electronic health record (EHR)-based, open-label, randomized, pragmatic clinical trial enrolling ∼16,500 participants within Kaiser Permanente Northern California (KPNC) – a fully integrated and learning health care delivery system with 21 hospitals and >255 ambulatory clinics serving ∼4.5 million members. Adults ≥50 years with established ASCVD and no prior history of coronavirus disease 2019 (COVID-19) will be prospectively identified and pre-randomized in a 1:10 allocation ratio (∼1,500 IPE: ∼15,000 usual care) stratified by age and previous respiratory health status to the intervention (IPE two grams by mouth twice daily with meals) vs. the control group (usual care) for a minimum follow-up duration of 6 months. The co-primary endpoints are moderate-to-severe laboratory-confirmed viral URI and worst clinical status due to a viral URI at any point in time. Conclusion: The MITIGATE study will inform clinical practice by providing evidence on the real-world clinical effectiveness of pre-treatment with IPE to prevent and/or reduce the sequelae of laboratory-confirmed viral URIs in a high-risk cohort of patients with established ASCVD.

Background: Acute kidney injury (AKI) is a heterogeneous clinical syndrome with varying causes, pathophysiology and outcomes; but staging AKI is predominantly by serum creatinine. We sought to identify AKI sub-groups (sub-phenotypes) more tightly linked to underlying pathophysiology and long-term clinical outcomes. Methods: We independently applied latent class analysis (LCA) and k-Means clustering, to 29 clinical, plasma and urinary biomarker parameters measured during hospitalization to identify AKI sub-phenotypes in the ASSESS-AKI Study. AKI sub-phenotype associations were examined with the composite of major adverse kidney events (MAKE), defined as incident or progressive chronic kidney disease, long-term dialysis, or all-cause death during study follow-up. Findings: Among 769 AKI patients both LCA and k-Means clustering identified two AKI sub-phenotypes. Class 1 was characterized by a higher prevalence of prior congestive heart failure and favorable blood inflammatory and urinary tubular injury biomarkers, while class 2 was characterized by higher rates of prior chronic kidney disease and less favorable biomarkers. After a median follow-up of 4.7 years, the risk for MAKE was higher with class 2 (adjusted hazard ratio 1.41; 95% CI, 1.08 to 1.84; p=0.01) compared with class 1, adjusting for demographics, hospital level factors and KDIGO Stage of AKI. The higher risk of MAKE among class 2 was explained by a higher risk of chronic kidney disease progression and dialysis. The top five variables that were different between class 1 and 2 included plasma and urinary biomarkers of inflammation and epithelial cell injury, while serum creatinine ranked 20th out of the 29 variables for differentiating class 1 and 2. Interpretation: In this analysis, we identify two molecularly distinct AKI sub-phenotypes with differing risk of long-term outcomes, independent of current criteria to risk stratify AKI. Future identification of AKI sub-phenotypes may facilitate linking therapies to underlying pathophysiology to prevent long-term sequalae after AKI. Funding: National Institute of Diabetes, Digestive and Kidney Diseases Declaration of Interest: None to declare. Ethical Approval: The study was approved by the Yale University, Vanderbilt University, Kaiser Permanente, and University of Washington Institutional Review Boards. Written informed consent was obtained from participants.

Patients with heart failure (HF) and preserved (HFpEF) or borderline preserved ejection fraction (HFbEF) outnumber patients with HF and reduced ejection fraction (HFrEF), but limited data exist on outcomes in community-based populations of these patients. We examined clinical outcomes in a diverse population of adults with HFrEF, HFbEF, and HFpEF. All adults with diagnosed HF from 2005 to 2012 in Kaiser Permanente Northern California were categorized by left ventricular systolic function as HFpEF (EF ≥50%), HFbEF (EF 41-49%), or HFrEF (EF ≤40%). Demographics, clinical characteristics, and therapies were obtained from electronic records. Outcomes included death, HF hospitalization, and HF-related emergency department (ED) visit. In 28,914 eligible HF patients, there were 52% HFpEF, 16% HFbEF, and 32% HFrEF, with mean age 72.8 years and 45% women. During median follow-up of 3.5 years, crude rates (per 100 person-years) of death, HF hospitalization, and HF-related ED visit were 14.5 (95% CI 14.3 to 14.7), 15.8 (15.5 to 16.0), and 38.2 (37.8 to 38.5), respectively. Compared with HFrEF patients, adjusted hazard ratios of death, HF hospitalization, and HF-related ED visit for HFpEF patients were 0.82 (0.79 to 0.85), 0.72 (0.68 to 0.75), and 0.94 (0.90 to 0.99), respectively, and for HFbEF patients were 0.84 (0.79 to 0.88), 0.79 (0.73 to 0.84), and 0.90 (0.84 to 0.96), respectively. In conclusion, within a large community-based HF cohort, adjusted rates of death, HF hospitalization, and HF-related ED visits were similar in HFpEF and HFbEF patients, but higher in HFrEF patients. Regardless of systolic function, however, long-term mortality and morbidity in all HF patients remain high, reinforcing the need for novel strategies to improve long-term outcomes.

BACKGROUND AND AIMS: Coronary artery calcification (CAC) is common among patients with chronic kidney disease (CKD) and predicts the risk for cardiovascular disease (CVD). We examined the associations of novel risk factors with CAC progression among patients with CKD. METHODS: Among 1,123 CKD patients in the Chronic Renal Insufficiency Cohort (CRIC) Study, CAC was measured in Agatston units at baseline and a follow-up visit using electron beam computed tomography or multidetector computed tomography. RESULTS: Over an average 3.3-year follow-up, 109 (25.1%) participants without CAC at baseline had incident CAC and 124 (18.0%) participants with CAC at baseline had CAC progression, defined as an annual increase of ≥100 Agatston units. After adjustment for established atherosclerotic risk factors, several novel risk factors were associated with changes in CAC over follow-up. Changes in square root transformed CAC score associated with 1 SD greater level of risk factors were −0.20 (95% confidence interval, −0.31 to −0.10; p

Rationale & Objective The clearance of protein-bound solutes by the proximal tubules is an innate kidney mechanism for removing putative uremic toxins that could exert cardiovascular toxicity in humans. However, potential associations between impaired kidney clearances of secretory solutes and cardiovascular events among patients with chronic kidney disease (CKD) remains uncertain. Study Design A multicenter, prospective, cohort study. Setting & Participants We evaluated 3,407 participants from the Chronic Renal Insufficiency Cohort (CRIC) study. Exposures Baseline kidney clearances of 8 secretory solutes. We measured concentrations of secretory solutes in plasma and paired 24-hour urine specimens using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Outcomes Incident heart failure, myocardial infarction, and stroke events. Analytical Approach We used Cox regression to evaluate associations of baseline secretory solute clearances with incident study outcomes adjusting for estimated GFR (eGFR) and other confounders. Results Participants had a mean age of 56 years; 45% were women; 41% were Black; and the median estimated glomerular filtration rate (eGFR) was 43 mL/min/1.73 m2. Lower 24-hour kidney clearance of secretory solutes were associated with incident heart failure and myocardial infarction but not incident stroke over long-term follow-up after controlling for demographics and traditional risk factors. However, these associations were attenuated and not statistically significant after adjustment for eGFR. Limitations Exclusion of patients with severely reduced eGFR at baseline; measurement variability in secretory solutes clearances. Conclusions In a national cohort study of CKD, no clinically or statistically relevant associations were observed between the kidney clearances of endogenous secretory solutes and incident heart failure, myocardial infarction, or stroke after adjustment for eGFR. These findings suggest that tubular secretory clearance provides little additional information about the development of cardiovascular disease events beyond glomerular measures of GFR and albuminuria among patients with mild-to-moderate CKD.

Rationale & Objective Cardiovascular events are less common in women than men in general populations; however, studies in chronic kidney disease (CKD) are less conclusive. We evaluated sex-related differences in cardiovascular events and death in adults with CKD. Study Design Prospective cohort study. Setting & Participants 1,778 women and 2,161 men enrolled in the Chronic Renal Insufficiency Cohort (CRIC). Exposure Sex (women vs men). Outcome Atherosclerotic composite outcome (myocardial infarction, stroke, or peripheral artery disease), incident heart failure, cardiovascular death, and all-cause death. Analytical Approach Cox proportional hazards regression. Results During a median follow-up period of 9.6 years, we observed 698 atherosclerotic events (women, 264; men, 434), 762 heart failure events (women, 331; men, 431), 435 cardiovascular deaths (women, 163; men, 274), and 1,158 deaths from any cause (women, 449; men, 709). In analyses adjusted for sociodemographic, clinical, and metabolic parameters, women had a lower risk of atherosclerotic events (HR, 0.71 [95% CI, 0.57-0.88]), heart failure (HR, 0.76 [95% CI, 0.62-0.93]), cardiovascular death (HR, 0.55 [95% CI, 0.42-0.72]), and death from any cause (HR, 0.58 [95% CI, 0.49-0.69]) compared with men. These associations remained statistically significant after adjusting for cardiac and inflammation biomarkers. Limitations Assessment of sex hormones, which may play a role in cardiovascular risk, was not included. Conclusions In a large, diverse cohort of adults with CKD, compared with men, women had lower risks of cardiovascular events, cardiovascular mortality, and mortality from any cause. These differences were not explained by measured cardiovascular risk factors.

The kidneys maintain acid-base homeostasis through excretion of acid as either ammonium or as titratable acids that primarily use phosphate as a buffer. In chronic kidney disease (CKD), ammoniagenesis is impaired, promoting metabolic acidosis. Metabolic acidosis stimulates phosphaturic hormones, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) in vitro, possibly to increase urine titratable acid buffers, but this has not been confirmed in humans. We hypothesized that higher acid load and acidosis would associate with altered phosphorus homeostasis, including higher urinary phosphorus excretion and serum PTH and FGF-23.Cross-sectional.980 participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.Net acid excretion as measured in 24-hour urine, potential renal acid load (PRAL) estimated from food frequency questionnaire responses, and serum bicarbonate concentration 22 mEq/L.24-hour urine phosphorus and calcium excretion and serum phosphorus, FGF-23, and PTH concentrations.Using linear and log-linear regression adjusted for demographics, kidney function, comorbid conditions, body mass index, diuretic use, and 24-hour urine creatinine excretion, we found that 24-hour urine phosphorus excretion was higher at higher net acid excretion, higher PRAL, and lower serum bicarbonate concentration (each P0.05). Serum phosphorus concentration was also higher with higher net acid excretion and lower serum bicarbonate concentration (each P=0.001). Only higher net acid excretion associated with higher 24-hour urine calcium excretion (P0.001). Neither net acid excretion nor PRAL was associated with FGF-23 or PTH concentrations. PTH, but not FGF-23, concentration (P=0.2) was 26% (95% CI, 13%-40%) higher in participants with a serum bicarbonate concentration 22 versus ≥22 mEq/L (P0.001). Primary results were similar if stratified by estimated glomerular filtration rate categories or adjusted for iothalamate glomerular filtration rate (n=359), total energy intake, dietary phosphorus, or urine urea nitrogen excretion, when available.Possible residual confounding by kidney function or nutrition; urine phosphorus excretion was included in calculation of the titratable acid component of net acid excretion.In CKD, higher acid load and acidosis associate independently with increased circulating phosphorus concentration and augmented phosphaturia, but not consistently with FGF-23 or PTH concentrations. This may be an adaptation that increases titratable acid excretion and thus helps maintain acid-base homeostasis in CKD. Understanding whether administration of base can lower phosphorus concentrations requires testing in interventional trials.

Background Diabetes is a well-established risk factor for thromboembolism in patients with atrial fibrillation (AF), but less is known about how diabetes influences outcomes among AF patients. Objectives This study assessed whether symptoms, health status, care, and outcomes differ between AF patients with and without diabetes. Methods The cohort study included 9,749 patients from the ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry, a prospective, nationwide, outpatient registry of patients with incident and prevalent AF. Outcomes included symptoms, health status, and AF treatment, as well as 2-year risk of death, hospitalization, thromboembolic events, heart failure (HF), and AF progression. Results Patients with diabetes (29.5%) were younger, more likely to have hypertension, chronic kidney disease, HF, coronary heart disease, and stroke. Compared to patients without diabetes, patients with diabetes also had a lower Atrial Fibrillation Effects on Quality of Life score of 80 (interquartile range [IQR]: 62.5 to 92.6) versus 82.4 (IQR: 67.6 to 93.5; p = 0.025) and were more likely to receive anticoagulation (p Conclusions Among AF patients, diabetes was associated with worse AF symptoms and lower quality of life, and increased risk of death and hospitalizations, but not thromboembolic or bleeding events.

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) 2 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/1.73m 2 , 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.

Inflammation is a consequence of chronic kidney disease (CKD) and is associated with adverse outcomes in many clinical settings. Inflammation stimulates production of fibroblast growth factor 23 (FGF23), high levels of which are independently associated with mortality in CKD. Few large-scale prospective studies have examined inflammation and mortality in patients with CKD, and none tested the interrelationships between inflammation, FGF23 and risk of death. Therefore, we conducted a prospective investigation of 3875 participants in the Chronic Renal Insufficiency Cohort (CRIC) study with CKD stages 2 to 4 to test the associations of baseline plasma interleukin-6, high sensitivity C-reactive protein, and FGF23 levels with all-cause mortality, censoring at the onset of end-stage renal disease. During a median follow-up of 6.9 years, 550 participants died (20.5/1000 person-years) prior to end stage renal disease. In separate multivariable-adjusted analyses, higher levels of interleukin-6 (hazard ratio per one standard deviation increase of natural log-transformed levels) 1.35 (95% confidence interval, 1.25–1.46), C-reactive protein 1.28 (1.16–1.40), and FGF23 1.45 (1.32–1.60) were each independently associated with increased risk of death. With further adjustment for FGF23, the risks of death associated with interleukin-6 and C-reactive protein were minimally attenuated. Compared to participants in the lowest quartiles of inflammation and FGF23, the multivariable-adjusted hazard ratio of death among those in the highest quartiles of both biomarkers was 4.38 (2.65–7.23) for interleukin-6 and FGF23, and 5.54 (3.04–10.09) for C-reactive protein and FGF23. Thus, elevated levels of interleukin-6, C-reactive protein and FGF23 are independent risk factors for mortality in CKD.

RATIONALE & OBJECTIVE: Digital and mobile health (mHealth) technologies improve patient-provider communication and increase information accessibility. We assessed technology use, attitudes toward using mHealth technologies, and the proficiency in using mHealth technologies among individuals with chronic kidney disease (CKD). STUDY DESIGN: Cross-sectional survey with open text responses SETTING & PARTICIPANTS: Chronic Renal Insufficiency Cohort Study participants who completed current use and interest in using mHealth technologies questionnaires, and the eHealth literacy Survey (eHEALS). EXPOSURES: Participant characteristics OUTCOMES: Technology use (internet/email/smartphone/mHealth applications [apps]), interest in future mHealth use, and proficiency in using digital and mHealth technologies, or eHealth literacy, determined by eHEALS score. ANALYTIC APPROACH: Poisson regression and a qualitative content analysis of open-ended responses RESULTS: Study participants (N=932) had a mean age of 68 years, eGFR 54 ml/min/1.73m(2), and 59% were male. Approximately 70% reported current use of internet/email/smartphones, and 35% used mHealth apps; only 27% had adequate eHealth literacy (eHEALS score ≥32). Participants