Mobile Health (mHealth) Technology: Assessment of Availability, Acceptability, and Use in CKD.

RATIONALE & OBJECTIVE: Digital and mobile health (mHealth) technologies improve patient-provider communication and increase information accessibility. We assessed the use of technology, attitudes toward using mHealth technologies, and 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 (CRIC) Study participants who completed current use and interest in using mHealth technologies questionnaires and the eHealth literacy Survey (eHEALS). EXPOSURE: Participant characteristics. OUTCOMES: Use of technology (ie, internet, email, smartphone, and mHealth applications [apps]), interest in future mHealth use, and proficiency in using digital and mHealth technologies, or eHealth literacy, determined by eHEALS score. ANALYTICAL APPROACH: Poisson regression and a qualitative content analysis of open-ended responses. RESULTS: Study participants (n = 932) had a mean age of 68 years old and an estimated glomerular filtration rate (eGFR) of 54 mL/min/1.73 m2, and 59% were male. Approximately 70% reported current use of internet, email, and smartphones, and 35% used mHealth apps; only 27% had adequate eHealth literacy (eHEALS score ≥ 32). Participants <65 years of age (vs. ≥65), with more education, higher income, better cognition, and adequate health literacy reported more use of technology, and greater interest in using technologies. Participants of White (vs. non-White) race reported more use of internet and email but less interest in future use of mHealth. Younger age, higher annual income, and greater disease self-efficacy were associated with adequate eHealth literacy. Three themes regarding interest in using digital and mHealth technologies emerged: willingness, concerns, and barriers. LIMITATIONS: Residual confounding, ascertainment bias. CONCLUSIONS: Many individuals with CKD currently use the internet and smartphones and are interested in using mHealth in the future, but few use mHealth apps or have adequate eHealth literacy. mHealth technologies present an opportunity to engage individuals with CKD, especially members of racial or ethnic minority groups because those groups reported greater interest in using mHealth technology than the nonminority population. Further research is needed to identify strategies to overcome inadequate eHealth literacy.

Incident Chronic Kidney Disease Risk among Hispanics/Latinos in the United States: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: Although Hispanics/Latinos in the United States are often considered a single ethnic group, they represent a heterogenous mixture of ancestries who can self-identify as any race defined by the U.S. Census. They have higher ESKD incidence compared with non-Hispanics, but little is known about the CKD incidence in this population. METHODS: We examined rates and risk factors of new-onset CKD using data from 8774 adults in the Hispanic Community Health Study/Study of Latinos. Incident CKD was defined as eGFR <60 ml/min per 1.73 m2 with eGFR decline ≥1 ml/min per 1.73 m2 per year, or urine albumin/creatinine ratio ≥30 mg/g. Rates and incidence rate ratios were estimated using Poisson regression with robust variance while accounting for the study's complex design. RESULTS: Mean age was 40.3 years at baseline and 51.6% were women. In 5.9 years of follow-up, 648 participants developed CKD (10.6 per 1000 person-years). The age- and sex-adjusted incidence rates ranged from 6.6 (other Hispanic/mixed background) to 15.0 (Puerto Ricans) per 1000 person-years. Compared with Mexican background, Puerto Rican background was associated with 79% increased risk for incident CKD (incidence rate ratios, 1.79; 95% confidence interval, 1.33 to 2.40), which was accounted for by differences in sociodemographics, acculturation, and clinical characteristics. In multivariable regression analysis, predictors of incident CKD included BP >140/90 mm Hg, higher glycated hemoglobin, lower baseline eGFR, and higher baseline urine albumin/creatinine ratio. CONCLUSIONS: CKD incidence varies by Hispanic/Latino heritage and this disparity may be in part attributed to differences in sociodemographic characteristics. Culturally tailored public heath interventions focusing on the prevention and control of risk factors might ameliorate the CKD burden in this population.

CKD and ESRD in US Hispanics.

Hispanics are the largest racial/ethnic minority group in the United States, and they experience a substantial burden of kidney disease. Although the prevalence of chronic kidney disease (CKD) is similar or slightly lower in Hispanics than non-Hispanic whites, the age- and sex-adjusted prevalence rate of end-stage renal disease is almost 50% higher in Hispanics compared with non-Hispanic whites. This has been attributed in part to faster CKD progression among Hispanics. Furthermore, Hispanic ethnicity has been associated with a greater prevalence of cardiovascular disease risk factors, including obesity and diabetes, as well as CKD-related complications. Despite their less favorable socioeconomic status, which often leads to limited access to quality health care, and their high comorbid condition burden, the risk for mortality among Hispanics appears to be lower than for non-Hispanic whites. This survival paradox has been attributed to a complex interplay between sociocultural and psychosocial factors, as well as other factors. Future research should focus on evaluating the long-term impact of these factors on patient-centered and clinical outcomes. National policies are needed to improve access to and quality of health care among Hispanics with CKD.

Genome-Wide Association of CKD Progression: The Chronic Renal Insufficiency Cohort Study.

The rate of decline of renal function varies significantly among individuals with CKD. To understand better the contribution of genetics to CKD progression, we performed a genome-wide association study among participants in the Chronic Renal Insufficiency Cohort Study. Our outcome of interest was CKD progression measured as change in eGFR over time among 1331 blacks and 1476 whites with CKD. We stratified all analyses by race and subsequently, diabetes status. Single-nucleotide polymorphisms (SNPs) that surpassed a significance threshold of P<1×10-6 for association with eGFR slope were selected as candidates for follow-up and secondarily tested for association with proteinuria and time to ESRD. We identified 12 such SNPs among black patients and six such SNPs among white patients. We were able to conduct follow-up analyses of three candidate SNPs in similar (replication) cohorts and eight candidate SNPs in phenotype-related (validation) cohorts. Among blacks without diabetes, rs653747 in LINC00923 replicated in the African American Study of Kidney Disease and Hypertension cohort (discovery P=5.42×10-7; replication P=0.039; combined P=7.42×10-9). This SNP also associated with ESRD (hazard ratio, 2.0 (95% confidence interval, 1.5 to 2.7); P=4.90×10-6). Similarly, rs931891 in LINC00923 associated with eGFR decline (P=1.44×10-4) in white patients without diabetes. In summary, SNPs in LINC00923, an RNA gene expressed in the kidney, significantly associated with CKD progression in individuals with nondiabetic CKD. However, the lack of equivalent cohorts hampered replication for most discovery loci. Further replication of our findings in comparable study populations is warranted.

Urine biomarkers of tubular injury do not improve on the clinical model predicting chronic kidney disease progression.

Few investigations have evaluated the incremental usefulness of tubular injury biomarkers for improved prediction of chronic kidney disease (CKD) progression. As such, we measured urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-ß-D-glucosaminidase and liver fatty acid binding protein under highly standardized conditions among 2466 enrollees of the prospective Chronic Renal Insufficiency Cohort Study. During 9433 person-years of follow-up, there were 581 cases of CKD progression defined as incident end-stage renal disease or halving of the estimated glomerular filtration rate. Levels of the urine injury biomarkers, normalized for urine creatinine, were strongly associated with CKD progression in unadjusted Cox proportional hazard models with hazard ratios in the range of 7 to 15 comparing the highest with the lowest quintiles. However, after controlling for the serum creatinine-based estimated glomerular filtration rate and urinary albumin/creatinine ratio, none of the normalized biomarkers was independently associated with CKD progression. None of the biomarkers improved on the high (0.89) C-statistic for the base clinical model. Thus, among patients with CKD, risk prediction with a clinical model that includes the serum creatinine-based estimated glomerular filtration rate and the urinary albumin/creatinine ratio is not improved on with the addition of renal tubular injury biomarkers.

CKD Progression and Mortality among Hispanics and Non-Hispanics.

Although recommended approaches to CKD management are achieved less often in Hispanics than in non-Hispanics, whether long-term outcomes differ between these groups is unclear. In a prospective longitudinal analysis of participants enrolled into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies, we used Cox proportional hazards models to determine the association between race/ethnicity, CKD progression (50% eGFR loss or incident ESRD), incident ESRD, and all-cause mortality, and linear mixed-effects models to assess differences in eGFR slope. Among 3785 participants, 13% were Hispanic, 43% were non-Hispanic white (NHW), and 44% were non-Hispanic black (NHB). Over a median follow-up of 5.1 years for Hispanics and 6.8 years for non-Hispanics, 27.6% of all participants had CKD progression, 21.3% reached incident ESRD, and 18.3% died. Hispanics had significantly higher rates of CKD progression, incident ESRD, and mean annual decline in eGFR than did NHW (P<0.05) but not NHB. Hispanics had a mortality rate similar to that of NHW but lower than that of NHB (P<0.05). In adjusted analyses, the risk of CKD progression did not differ between Hispanics and NHW or NHB. However, among nondiabetic participants, compared with NHB, Hispanics had a lower risk of CKD progression (hazard ratio, 0.61; 95% confidence interval, 0.39 to 0.95) and incident ESRD (hazard ratio, 0.50; 95% confidence interval, 0.30 to 0.84). At higher levels of urine protein, Hispanics had a significantly lower risk of mortality than did non-Hispanics (P<0.05). Thus, important differences in CKD progression and mortality exist between Hispanics and non-Hispanics and may be affected by proteinuria and diabetes.

Different components of blood pressure are associated with increased risk of atherosclerotic cardiovascular disease versus heart failure in advanced chronic kidney disease.

Blood pressure is a modifiable risk for cardiovascular disease (CVD). Among hemodialysis patients, there is a U-shaped association between blood pressure and risk of death. However, few studies have examined the association between blood pressure and CVD in patients with stage 4 and 5 chronic kidney disease. Here we studied 1795 Chronic Renal Insufficiency Cohort (CRIC) Study participants with estimated glomerular filtration rate <30 ml/min per 1.73 m2 and not on dialysis. The association of systolic (SBP), diastolic (DBP), and pulse pressure with the risk of physician-adjudicated atherosclerotic CVD (stroke, myocardial infarction, or peripheral arterial disease) and heart failure was tested using Cox regression adjusted for demographics, comorbidity and medications. There was a significant association with higher SBP (adjusted hazard ratio 2.04 [95% confidence interval: 1.46-2.84]) for SBP over 140 vs under 120 mmHg, higher DBP (2.52 [1.54-4.11]) for DBP >90 mm Hg versus <80 mm Hg and higher pulse pressure (2.67 [1.82-3.92]) for pulse pressure >68 mm Hg versus <51 mm Hg with atherosclerotic CVD. For heart failure, there was a significant association with higher pulse pressure only (1.42 [1.05-1.92]) for pulse pressure >68 mm Hg versus <51 mmHg, but not for SBP or DBP. Thus, among participants with stage 4 and 5 chronic kidney disease, there was an independent association between higher SBP, DBP, and pulse pressure with the risk of atherosclerotic CVD, whereas only higher pulse pressure was independently associated with a greater risk of heart failure. Further trials are needed to determine whether aggressive reduction of blood pressure decreases the risk of CVD events in patients with stage 4 and 5 chronic kidney disease.

Traditional and non-traditional risk factors for incident peripheral arterial disease among patients with chronic kidney disease.

BACKGROUND: The risk of peripheral arterial disease (PAD) is higher in patients with chronic kidney disease (CKD) compared with those without. However, reasons for this increased risk are not fully understood. METHODS: We studied risk factors for incident PAD among 3169 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. Patients with CKD aged 21-74 years were recruited between 2003 and 2008 and followed for a median of 6.3 years. Incident PAD was defined as a new onset ankle-brachial index (ABI) of <0.9 or confirmed clinical PAD. RESULTS: In a multivariate-adjusted model, older age, female sex, non-Hispanic Black, current smoking, diabetes, higher pulse pressure, lower high-density lipoprotein cholesterol, higher low-density lipoprotein cholesterol, and lower estimated glomerular filtration rate were significantly associated with the increased risk of incident PAD. After adjustment for these traditional risk factors as well as use of medications and CRIC Study clinic sites, the following baseline novel risk factors were significantly associated with risk of incident PAD [hazard ratio and 95% confidence interval (CI) for a one standard deviation (SD) higher level]: log[C-reactive protein (CRP)] (1.16, 1.06-1.25, P < 0.001), white blood cell count (1.09, 1.01-1.18, P = 0.03), fibrinogen (1.15, 1.06-1.26, P = 0.002), log(myeloperoxidase) (1.12, 1.03-1.23, P = 0.01), uric acid (0.88, 0.80-0.97, P = 0.01), glycated hemoglobin (1.16, 1.05-1.27, P = 0.003), log(homeostatic model assessment-insulin resistance) (1.21, 1.10-1.32, P < 0.001) and alkaline phosphatase (1.15, 1.07-1.24, P < 0.001). CONCLUSIONS: Among patients with CKD, inflammation, prothrombotic state, oxidative stress, glycated hemoglobin, insulin resistance and alkaline phosphatase are associated with an increased risk of PAD, independent of traditional risk factors.

Limited health literacy is associated with low glomerular filtration in the Chronic Renal Insufficiency Cohort (CRIC) study.

BACKGROUND: Low health literacy in the general population is associated with increased risk of death and hospitalization. The evaluation of health literacy in individuals with predialysis chronic kidney disease (CKD) is limited. METHODS: We conducted a cross-sectional study to evaluate the associations of limited health literacy with kidney function and cardiovascular disease (CVD) risk factors in 2,340 non-Hispanic (NH) Whites and Blacks aged 21 - 74 years with mild-to-moderate CKD. Limited health literacy was defined as a Short Test of Functional Health Literacy in Adults (STOFHLA) score ≤ 22. Outcomes evaluated included estimated glomerular filtration rate (eGFR), 24-hour urine protein excretion, and CVD risk factors. RESULTS: The prevalence of limited health literacy was 28% in NH-Blacks and 5% in NH-Whites. Compared with participants with adequate health literacy, those with limited health literacy were more likely to have lower eGFR (34 vs. 42 mL/min/1.73 m2); higher urine protein/24-hours (0.31 vs. 0.15 g); and higher self-reported CVD (61 vs. 37%); and were less likely to have BP < 130/80 mmHg (51 vs. 58%); p ≤ 0.01 for each comparison. After adjustment, limited health literacy was associated with self-reported CVD (OR 1.51, 95% CI 1.13 - 2.03) and lower eGFR (ß -2.47, p = 0.03). CONCLUSION: In this CKD cohort, limited health literacy was highly prevalent, especially among NH-Blacks, and it was associated with lower eGFR and a less favorable CVD risk factor profile. Further studies are needed to better understand these associations and inform the development of health literacy interventions among individuals with CKD.

Altered transcriptomic immune responses of maintenance hemodialysis patients to the COVID-19 mRNA vaccine.

Background: End-stage renal disease (ESRD) patients experience immune compromise characterized by complex alterations of both innate and adaptive immunity, and results in higher susceptibility to infection and lower response to vaccination. This immune compromise, coupled with greater risk of exposure to infectious disease at hemodialysis (HD) centers, underscores the need for examination of the immune response to the COVID-19 mRNA-based vaccines. Methods: The immune response to the COVID-19 BNT162b2 mRNA vaccine was assessed in 20 HD patients and cohort-matched controls. RNA sequencing of peripheral blood mononuclear cells was performed longitudinally before and after each vaccination dose for a total of six time points per subject. Anti-spike antibody levels were quantified prior to the first vaccination dose (V1D0) and 7 d after the second dose (V2D7) using anti-spike IgG titers and antibody neutralization assays. Anti-spike IgG titers were additionally quantified 6 mo after initial vaccination. Clinical history and lab values in HD patients were obtained to identify predictors of vaccination response. Results: Transcriptomic analyses demonstrated differing time courses of immune responses, with prolonged myeloid cell activity in HD at 1 wk after the first vaccination dose. HD also demonstrated decreased metabolic activity and decreased antigen presentation compared to controls after the second vaccination dose. Anti-spike IgG titers and neutralizing function were substantially elevated in both controls and HD at V2D7, with a small but significant reduction in titers in HD groups (p<0.05). Anti-spike IgG remained elevated above baseline at 6 mo in both subject groups. Anti-spike IgG titers at V2D7 were highly predictive of 6-month titer levels. Transcriptomic biomarkers after the second vaccination dose and clinical biomarkers including ferritin levels were found to be predictive of antibody development. Conclusions: Overall, we demonstrate differing time courses of immune responses to the BTN162b2 mRNA COVID-19 vaccination in maintenance HD subjects comparable to healthy controls and identify transcriptomic and clinical predictors of anti-spike IgG titers in HD. Analyzing vaccination as an in vivo perturbation, our results warrant further characterization of the immune dysregulation of ESRD. Funding: F30HD102093, F30HL151182, T32HL144909, R01HL138628. This research has been funded by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) award UL1TR002003.

Association of serum bicarbonate with risk of renal and cardiovascular outcomes in CKD: a report from the Chronic Renal Insufficiency Cohort (CRIC) study.

BACKGROUND: The purpose of this study is to evaluate serum bicarbonate level as a risk factor for renal outcomes, cardiovascular events, and mortality in patients with chronic kidney disease (CKD). STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 3,939 participants with CKD stages 2-4 who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 and December 2008. PREDICTOR: Serum bicarbonate level. OUTCOMES: Renal outcomes, defined as end-stage renal disease (either initiation of dialysis therapy or kidney transplantation) or 50% reduction in estimated glomerular filtration rate (eGFR); atherosclerotic events (myocardial infarction, stroke, or peripheral arterial disease); congestive heart failure events; and death. MEASUREMENTS: Time to event. RESULTS: Mean eGFR was 44.8 ± 16.8 (SD) mL/min/1.73 m(2), and median serum bicarbonate level was 24 (IQR, 22-26) mEq/L. During a median follow-up of 3.9 years, 374 participants died, 767 had a renal outcome, 332 experienced an atherosclerotic event, and 391 had a congestive heart failure event. In adjusted analyses, the risk of developing a renal end point was 3% lower per 1-mEq/L increase in serum bicarbonate level (HR, 0.97; 95% CI, 0.94-0.99; P = 0.01). The association was stronger for participants with eGFR >45 mL/min/1.73 m(2) (HR, 0.91; 95% CI, 0.85-0.97; P = 0.004). The risk of heart failure increased by 14% (HR, 1.14; 95% CI, 1.03-1.26; P = 0.02) per 1-mEq/L increase in serum bicarbonate level over 24 mEq/L. Serum bicarbonate level was not associated independently with atherosclerotic events (HR, 0.99; 95% CI, 0.95-1.03; P = 0.6) and all-cause mortality (HR, 0.98; 95% CI, 0.95-1.02; P = 0.3). LIMITATIONS: Single measurement of sodium bicarbonate. CONCLUSIONS: In a cohort of participants with CKD, low serum bicarbonate level was an independent risk factor for kidney disease progression, particularly for participants with preserved kidney function. The risk of heart failure was higher at the upper extreme of serum bicarbonate levels. There was no association between serum bicarbonate level and all-cause mortality or atherosclerotic events.

ACE inhibitor and ARB medication use among Medicaid enrollees with diabetes.

OBJECTIVE: To examine ace-inhibitor (ACEI) and angiotensin receptor blockers (ARB) prescription and adherence patterns by race in diabetic public aid recipients. DESIGN, PARTICIPANTS, AND MEASURES: We analyzed prescription records of 27,529 adults aged 18-64 with diabetes who had at least one clinical indication for receiving an ACEI/ ARB prescription and were enrolled in the State of Illinois public aid program during 2007. We calculated proportion of days covered (PDC) to assess adherence. Multivariate models adjusted for age, sex, ACEI/ARB indication, and any significant interaction terms. RESULTS: Only 47.4% of individuals with at least one indication for ACEI/ARB had filled an ACEI/ARB prescription. African American men were more likely than Caucasian men to ever fill an ACEI/ARB prescription (adjusted odds ratio, [AOR] [95% CI] 1.69 [1.55-1.83]). Hispanic English and Spanish speaking men were also more likely than Caucasian men to ever fill an ACEI/ARB prescription (AOR [95% CI] 1.37 [1.16-1.62] and 1.27 [1.05-1.53], respectively). Similarly, African American and Hispanic English and Spanish speaking women were more likely than Caucasian women to ever fill an ACEI/ARB prescription (AOR [95% CI] 1.70 [1.59-1.81], 1.55 (1.36-1.76), and 1.98 (1.73-2.28), respectively. However, African Americans and Hispanics were less likely than Caucasians to achieve a PDC> or =80%. Compared to Caucasians, Hispanic Spanish speakers were the least likely to be adherent (AOR [95% CI] .49 [.41-.58]). Furthermore, older individuals were more likely to achieve a PDC> or =80% than younger individuals. CONCLUSION: African Americans and Hispanics with diabetes receiving public aid in Illinois were more likely than Caucasians to have filled at least one ACEI/ARB prescription. However, they were less adherent with these medications. Future studies should assess barriers to medication adherence in this population.

Validation of the Kidney Disease Quality of Life Short Form 36 (KDQOL-36) US Spanish and English versions in a cohort of Hispanics with chronic kidney disease.

OBJECTIVE: Evaluate the reliability and validity of the Kidney Disease Quality of Life Short Form 36 (KDQOL-36) in Hispanics with mild-to-moderate chronic kidney disease (CKD). DESIGN: Cross-sectional SETTING: Chronic Renal Insufficiency Cohort Study PARTICIPANTS: 420 Hispanic (150 English- and 270 Spanish-speakers), and 409 non-Hispanic White individuals, matched by age (mean 57 years), sex (60% male), kidney function (mean estimated glomerular filtration rate 36ml/min/1.73m2), and diabetes (70%). METHODS: To measure construct validity, we selected instruments, comorbidities, and laboratory tests related to at least one KDQOL-36 subscale. Reliability was determined by calculating Cronbach's alpha. RESULTS: Reliability of each KDQOL-36 subscale [SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS), Symptoms/Problems, Burden of Kidney Disease and Effects of Kidney Disease] was very good (Cronbach's alpha >0.8). Construct validity was supported by expected negative correlation between MCS scores and the Beck Depression Inventory in all three subgroups (r=-0.56 to -0.61, P<.0001). There was inverse correlation between the Symptoms/ Problems subscale and the Patient Symptom Form (r= -0.70 to -0.77, P<.0001). We also found significant, positive correlation between the PCS score and a physical activity survey (r=+0.29 to +0.38, P< or =.003); and between the PCS and MCS scores and the Kansas City Questionnaire (r= +0.31 to +0.64, P<.0001). Reliability and validity were similar across all racial/ethnic groups analyzed separately. CONCLUSION: Our findings support the use of the KDQOL-36 as a measure of HRQOL in this cohort of US Hispanics with CKD.

Positive Psychological Intervention Delivered Using Virtual Reality in Patients on Hemodialysis With Comorbid Depression: Protocol and Design for the Joviality Randomized Controlled Trial.

BACKGROUND: Depression is highly prevalent in individuals on hemodialysis, but it is infrequently identified and remains undertreated. In this paper, we present details of the methodology of a randomized controlled trial (RCT) aimed at testing the feasibility and preliminary efficacy of a 5-week positive psychological intervention in individuals on hemodialysis with comorbid depression delivered using immersive virtual reality (VR) technology. OBJECTIVE: We aim to describe the protocol and design of the Joviality trial whose main objectives are 2-fold: determine the feasibility of the Joviality VR software through metrics capturing rates of recruitment, refusal, retention, noncompliance, and adherence, as well as end-user feedback; and assess preliminary efficacy for outcomes measures of depressive symptoms, psychological well-being and distress, quality of life, treatment adherence, clinical biomarkers, and all-cause hospitalizations. METHODS: This 2-arm RCT is scheduled to enroll 84 individuals on hemodialysis with comorbid depression from multiple outpatient centers in Chicago, Illinois, United States. Enrollees will be randomized to the following groups: VR-based Joviality positive psychological intervention or sham VR (2D wildlife footage and nature-based settings with inert music presented using a head-mounted display). To be eligible, individuals must be on hemodialysis for at least 3 months, have Beck Depression Inventory-II scores of ≥11 (ie, indicative of mild-to-severe depressive symptoms), be aged ≥21 years, and be fluent in English or Spanish. The Joviality VR software was built using agile design principles and incorporates fully immersive content, digital avatars, and multiplex features of interactability. Targeted skills of the intervention include noticing positive events, positive reappraisal, gratitude, acts of kindness, and mindful or nonjudgmental awareness. The primary outcomes include metrics of feasibility and acceptability, along with preliminary efficacy focused on decreasing symptoms of depression. The secondary and tertiary outcomes include quality of life, treatment adherence, clinical biomarkers, and all-cause hospitalization rates. There are 4 assessment time points: baseline, immediately after the intervention, 3 months after the intervention, and 6 months after the intervention. We hypothesize that depressive symptoms and hemodialysis-related markers of disease will substantially improve in participants randomized to the VR-based Joviality positive psychology treatment arm compared with those in the attention control condition. RESULTS: This RCT is funded by the National Institute of Diabetes and Digestive and Kidney Diseases and is scheduled to commence participant recruitment in June 2023. CONCLUSIONS: This trial will be the first to test custom-built VR software to deliver a positive psychological intervention, chairside, in individuals on hemodialysis to reduce symptoms of depression. Within the context of an RCT using an active control arm, if proven effective, VR technology may become a potent tool to deliver mental health programming in clinical populations during their outpatient treatment sessions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05642364; https://clinicaltrials.gov/ct2/show/NCT05642364. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/45100.

Immune response to the mRNA COVID-19 vaccine in hemodialysis patients: cohort study.

Background: End-stage renal disease (ESRD) patients experience immune compromise characterized by complex alterations of both innate and adaptive immunity, and results in higher susceptibility to infection and lower response to vaccination. This immune compromise, coupled with greater risk of exposure to infectious disease at hemodialysis (HD) centers, underscores the need for examination of the immune response to the COVID-19 mRNA-based vaccines. Methods: A transcriptomic analysis of the immune response to the Covid-19 BNT162b2 mRNA vaccine was assessed in 20 HD patients and cohort-matched controls. RNA sequencing of peripheral blood mononuclear cells (PBMCs) was performed longitudinally before and after each vaccination dose for a total of six time points per subject. Anti-spike antibody levels were quantified prior to the first vaccination dose (V1D0) and seven days after the second dose (V2D7) using anti-Spike IgG titers and antibody neutralization assays. Anti-spike IgG titers were additionally quantified six months after initial vaccination. Clinical history and lab values in HD patients were obtained to identify predictors of vaccination response. Results: Transcriptomic analyses demonstrated differing time courses of immune responses, with predominant T cell activity in controls one week after the first vaccination dose, compared to predominant myeloid cell activity in HD at this time point. HD demonstrated decreased metabolic activity and decreased antigen presentation compared to controls after the second vaccination dose. Anti-spike IgG titers and neutralizing function were substantially elevated in both controls and HD at V2D7, with a small but significant reduction in titers in HD groups (p < 0.05). Anti-spike IgG remained elevated above baseline at six months in both subject groups. Anti-spike IgG titers at V2D7 were highly predictive of 6-month titer levels. Transcriptomic biomarkers after the second vaccination dose and clinical biomarkers including ferritin levels were found to be predictive of antibody development. Conclusion: Overall, we demonstrate differing time courses of immune responses to the BTN162b2 mRNA COVID-19 vaccination in maintenance hemodialysis subjects (HD) comparable to healthy controls (HC) and identify transcriptomic and clinical predictors of anti-Spike IgG titers in HD. Analyzing vaccination as an in vivo perturbation, our results warrant further characterization of the immune dysregulation of end stage renal disease (ESRD). Funding: F30HD102093, F30HL151182, T32HL144909, R01HL138628This research has been funded by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) award UL1TR002003.

Aspirin for Primary and Secondary Prevention of Mortality, Cardiovascular Disease, and Kidney Failure in the Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale and Objective: Chronic kidney disease is a risk enhancing factor for cardiovascular disease (CVD) and mortality, and the role of aspirin use is unclear in this population. We investigated the risk and benefits of aspirin use in primary and secondary prevention of CVD in the Chronic Renal Insufficiency Cohort Study. Study Design: Prospective observational cohort. Setting & Participants: 3,664 Chronic Renal Insufficiency Cohort participants. Exposure: Aspirin use in patients with and without preexisting CVD. Outcomes: Mortality, composite and individual CVD events (myocardial infarction, stroke, and peripheral arterial disease), kidney failure (dialysis and transplant), and major bleeding. Analytical Approach: Intention-to-treat analysis and multivariable Cox proportional hazards model to examine associations of time varying aspirin use. Results: The primary prevention group was composed of 2,578 (70.3%) individuals. Mean age was 57 ± 11 years, 46% women, 42% Black, and 47% had diabetes. The mean estimated glomerular filtration rate was 45 mL/min/1.73 m2. Median follow-up was 11.5 (IQR, 7.4-13) years. Aspirin was not associated with all-cause mortality in those without preexisting cardiovascular disease (CVD) (HR, 0.84; 95% CI, 0.7-1.01; P = 0.06) or those with CVD (HR, 0.88; 95% CI, 0.77-1.02, P = 0.08). Aspirin was not associated with a reduction of the CVD composite in primary prevention (HR, 0.97; 95% CI, 0.77-1.23; P = 0.79) and in secondary prevention because the original study design was not meant to study the effects of aspirin. Limitations: This is not a randomized controlled trial, and therefore, causality cannot be determined. Conclusions: Aspirin use in chronic kidney disease patients was not associated with reduction in primary or secondary CVD events, progression to kidney failure, or major bleeding.

Emergency Department/Urgent Care as Usual Source of Care and Clinical Outcomes in CKD: Findings From the Chronic Renal Insufficiency Cohort Study.

Rationale & Objective: Having a usual source of care increases use of preventive services and is associated with improved survival in the general population. We evaluated this association in adults with chronic kidney disease (CKD). Study Design: Prospective, observational cohort study. Setting & Participants: Adults with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictor: Usual source of care was self-reported as: 1) clinic, 2) emergency department (ED)/urgent care, 3) other. Outcomes: Primary outcomes included incident end-stage kidney disease (ESKD), atherosclerotic events (myocardial infarction, stroke, or peripheral artery disease), incident heart failure, hospitalization events, and all-cause death. Analytical Approach: Multivariable regression analyses to evaluate the association between usual source of care (ED/urgent care vs clinic) and primary outcomes. Results: Among 3,140 participants, mean age was 65 years, 44% female, 45% non-Hispanic White, 43% non-Hispanic Black, and 9% Hispanic, mean estimated glomerular filtration rate 50 mL/min/1.73 m2. Approximately 90% identified clinic as usual source of care, 9% ED/urgent care, and 1% other. ED/urgent care reflected a more vulnerable population given lower baseline socioeconomic status, higher comorbid condition burden, and poorer blood pressure and glycemic control. Over a median follow-up time of 3.6 years, there were 181 incident end-stage kidney disease events, 264 atherosclerotic events, 263 incident heart failure events, 288 deaths, and 7,957 hospitalizations. Compared to clinic as usual source of care, ED/urgent care was associated with higher risk for all-cause death (HR, 1.53; 95% CI, 1.05-2.23) and hospitalizations (RR, 1.41; 95% CI, 1.32-1.51). Limitations: Cannot be generalized to all patients with CKD. Causal relationships cannot be established. Conclusions: In this large, diverse cohort of adults with moderate-to-severe CKD, those identifying ED/urgent care as usual source of care were at increased risk for death and hospitalizations. These findings highlight the need to develop strategies to improve health care access for this high-risk population.

Progression of CKD in Hispanics: potential roles of health literacy, acculturation, and social support.

Hispanics are the fastest growing minority group in the United States, and compared with non-Hispanic whites, they have a higher incidence of end-stage renal disease. Examining novel factors that may explain this disparity in progression of chronic kidney disease (CKD) in Hispanics is urgently needed. Interpersonal and patient-centered characteristics, including health literacy, acculturation, and social support, have been shown to affect health outcomes in patients with other chronic diseases. However, these characteristics have not been well studied in the context of CKD, particularly in relation to disease knowledge, attitudes, and behaviors. In this report, we examine the potential roles of these factors for CKD progression in Hispanics and propose targeted therapeutic interventions.

CKD in Hispanics: Baseline characteristics from the CRIC (Chronic Renal Insufficiency Cohort) and Hispanic-CRIC Studies.

BACKGROUND: Little is known regarding chronic kidney disease (CKD) in Hispanics. We compared baseline characteristics of Hispanic participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies with non-Hispanic CRIC participants. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: Participants were aged 21-74 years with CKD using age-based estimated glomerular filtration rate (eGFR) at enrollment into the CRIC/H-CRIC Studies. H-CRIC included Hispanics recruited at the University of Illinois in 2005-2008, whereas CRIC included Hispanics and non-Hispanics recruited at 7 clinical centers in 2003-2007. FACTOR: Race/ethnicity. OUTCOMES: Blood pressure, angiotensin-converting enzyme (ACE)-inhibitor/angiotensin receptor blocker (ARB) use, and CKD-associated complications. MEASUREMENTS: Demographic characteristics, laboratory data, blood pressure, and medications were assessed using standard techniques and protocols. RESULTS: Of H-CRIC/CRIC participants, 497 were Hispanic, 1,650 were non-Hispanic black, and 1,638 were non-Hispanic white. Low income and educational attainment were nearly twice as prevalent in Hispanics compared with non-Hispanics (P < 0.01). Hispanics had self-reported diabetes (67%) more frequently than non-Hispanic blacks (51%) and whites (40%; P < 0.01). Blood pressure >130/80 mm Hg was more common in Hispanics (62%) than blacks (57%) and whites (35%; P < 0.05), and abnormalities in hematologic, metabolic, and bone metabolism parameters were more prevalent in Hispanics (P < 0.05), even after stratifying by entry eGFR. Hispanics had the lowest use of ACE inhibitors/ARBs among the high-risk subgroups, including participants with diabetes, proteinuria, and blood pressure >130/80 mm Hg. Mean eGFR was lower in Hispanics (39.6 mL/min/1.73 m(2)) than in blacks (43.7 mL/min/1.73 m(2)) and whites (46.2 mL/min/1.73 m(2)), whereas median proteinuria was higher in Hispanics (protein excretion, 0.72 g/d) than in blacks (0.24 g/d) and whites (0.12 g/d; P < 0.01). LIMITATIONS: Generalizability; observed associations limited by residual bias and confounding. CONCLUSIONS: Hispanics with CKD in the CRIC/H-CRIC Studies are disproportionately burdened with lower socioeconomic status, more frequent diabetes mellitus, less ACE-inhibitor/ARB use, worse blood pressure control, and more severe CKD and associated complications than their non-Hispanic counterparts.

Atherosclerotic Cardiovascular Disease Events in Adults With CKD Taking a Moderate- or High-Intensity Statin: The Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline uses risk stratification to guide the decision to initiate nonstatin lipid-lowering medication among adults with atherosclerotic cardiovascular disease (CVD). We determined atherosclerotic CVD (ASCVD) event rates among adults with chronic kidney disease (CKD) taking statin therapy within 2018 AHA/ACC cholesterol guideline risk categories. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Adults with CKD not on dialysis in the Chronic Renal Insufficiency Cohort (CRIC) study who were taking a moderate/high-intensity statin 1 year after enrollment (baseline for the current analysis, n = 1,753). EXPOSURE: 2018 AHA/ACC cholesterol guideline risk categories: without a history of ASCVD, a history of 1 major ASCVD event and multiple high-risk conditions, and a history of ≥2 major ASCVD events. OUTCOME: Adjudicated ASCVD events after the year 1 study visit. ANALYTICAL APPROACH: We calculated age-sex standardized rates for ASCVD events and age-sex adjusted hazard ratios for ASCVD events accounting for the competing risk of death. RESULTS: There were 394 ASCVD events over a median follow-up period of 8 years. The ASCVD event rates (with 95% CI) per 1,000 person-years among participants without a history of ASCVD, with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 21.7 (18.4-25.1), 45.0 (37.8-52.3), and 73.3 (53.3-93.4), respectively. Compared with participants without a history of ASCVD, the HR (95% CI) rates for ASCVD events among those with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 1.89 (1.52-2.36) and 2.50 (1.85-3.39), respectively. LIMITATIONS: Data on whether participants were taking a maximally tolerated statin dosage were unavailable. CONCLUSIONS: The 2018 AHA/ACC cholesterol guideline identifies adults with CKD who have very high ASCVD risk despite taking a moderate/high-intensity statin.