An Intervention to Reduce Sedentary Behavior in Adults with Chronic Kidney Disease: A Feasibility Study.

Adults with chronic kidney disease (CKD) tend to be extremely sedentary. We investigated the feasibility and acceptability of a sedentary-reducing intervention for adults with CKD. The intervention utilized telephone-delivered coaching and a consumer wearable device to support participants to reduce their sedentary time. The mean age of participants in the sample was 60.5 years; 72% were women, and 83% had CKD Stage 3. At baseline, participants spent 73% of their waking time sedentary. Inter vention phone call attendance was 100%, study retention was 82%, and the intervention was rated as enjoyable (9.1/10). A telephone-delivered, sedentary-reducing intervention is feasible and acceptable in adults with CKD. Future work is needed investigating the efficacy of sedentary-reducing interventions for adults with CKD.

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

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

Diets high in subsidized foods and chronic kidney disease in Hispanic communities in the United States: the Hispanic Community Health Study/Study of Latinos.

Prior research shows that diets high in government subsidized foods may be associated with cardiometabolic disease risk factors. Our aim was to evaluate the relationship between diets high in subsidized foods and the development of chronic kidney disease (CKD) and other cardiometabolic risk factors in United States (US) Hispanics/Latinos. Using data from 16,172 Hispanics/Latino's living in the United States, we used the Cochran-Armitage test to assess the relationship between subsidized foods in the diets of participants and baseline characteristics. We used survey-weighted Poisson regression models to examine whether intake of subsidized foods was associated with incident CKD or cardiometabolic risk factors. Several baseline characteristics were associated with higher subsidized food scores. Higher subsidized food scores were not associated with incident CKD or cardiometabolic risk factors. These findings may be useful for future researchers, clinicians, and nutritional policy advocates who are interested in the way Hispanic and Latinos consume foods subsidized by the US government and the structural factors that may shape observed dietary and disease patterns.

Depressive Symptoms, Antidepressants, and Clinical Outcomes in Chronic Kidney Disease: Findings from the CRIC Study.

Rationale & Objective: The extent to which depression affects the progression of chronic kidney disease (CKD) and leads to adverse clinical outcomes remains inadequately understood. We examined the association of depressive symptoms (DS) and antidepressant medication use on clinical outcomes in 4,839 adults with nondialysis CKD. Study Design: Observational cohort study. Setting and Participants: Adults with mild to moderate CKD who participated in the multicenter Chronic Renal Insufficiency Cohort Study (CRIC). Exposure: The Beck Depression Inventory (BDI) was used to quantify DS. Antidepressant use was identified from medication bottles and prescription lists. Individual effects of DS and antidepressants were examined along with categorization as follows: (1) BDI <11 and no antidepressant use, (2) BDI <11 with antidepressant use, (3) BDI ≥11 and no antidepressant use, and (4) BDI ≥11 with antidepressant use. Outcomes: CKD progression, incident cardiovascular disease composite, all-cause hospitalizations, and mortality. Analytic Approach: Cox regression models were fitted for outcomes of CKD progression, incident cardiovascular disease, and all-cause mortality, whereas hospitalizations used Poisson regression. Results: At baseline, 27.3% of participants had elevated DS, and 19.7% used antidepressants. Elevated DS at baseline were associated with significantly greater risk for an incident cardiovascular disease event, hospitalization, and all-cause mortality, but not CKD progression, adjusted for antidepressants. Antidepressant use was associated with higher risk for all-cause mortality and hospitalizations, after adjusting for DS. Compared to participants without elevated DS and not using antidepressants, the remaining groups (BDI <11 with antidepressants; BDI ≥11 and no antidepressants; BDI ≥11 with antidepressants) showed higher risks of hospitalization and all-cause mortality. Limitations: Inability to infer causality among depressive symptoms, antidepressants, and outcomes. Additionally, the absence of nonpharmacological data, and required exploration of generalizability and alternative analytical approaches. Conclusions: Elevated DS increased adverse outcome risk in nondialysis CKD, unattenuated by antidepressants. Additionally, investigation into the utilization and counterproductivity of antidepressants in this population is warranted.

We analyzed data from 4,839 nondialysis chronic kidney disease (CKD) patients in the Chronic Renal Insufficiency Cohort Study to explore how depression and antidepressants affect CKD-related outcomes. Using the Beck Depression Inventory (BDI), we assessed depressive symptoms (DS) and identified antidepressant use through medication records. Outcomes included CKD progression, cardiovascular events, hospitalizations, and mortality. Elevated DS at baseline raised the risk of cardiovascular events, hospitalizations, and mortality, regardless of antidepressant use. Antidepressant use alone was associated with higher mortality and hospitalization risks. In comparison to those without elevated DS and no antidepressant use, all other groups faced increased hospitalization and mortality risks. Elevated DS posed a significant risk to nondialysis CKD patients, and antidepressants did not mitigate this risk.

Cumulative All-Cause Mortality in Diverse Hispanic/Latino Adults : A Prospective, Multicenter Cohort Study.

BACKGROUND: All-cause mortality among diverse Hispanic/Latino groups in the United States and factors underlying mortality differences have not been examined prospectively. OBJECTIVE: To describe cumulative all-cause mortality (and factors underlying differences) by Hispanic/Latino background, before and during the COVID-19 pandemic. DESIGN: Prospective, multicenter cohort study. SETTING: Hispanic Community Health Study/Study of Latinos. PARTICIPANTS: 15 568 adults aged 18 to 74 years at baseline (2008 to 2011) of Central American, Cuban, Dominican, Mexican, Puerto Rican, South American, and other backgrounds from the Bronx, New York; Chicago, Illinois; Miami, Florida; and San Diego, California. MEASUREMENTS: Sociodemographic, acculturation-related, lifestyle, and clinical factors were assessed at baseline, and vital status was ascertained through December 2021 (969 deaths; 173 444 person-years of follow-up). Marginally adjusted cumulative all-cause mortality risks (11-year before the pandemic and 2-year during the pandemic) were examined using progressively adjusted Cox regression. RESULTS: Before the pandemic, 11-year cumulative mortality risks adjusted for age and sex were higher in the Puerto Rican and Cuban groups (6.3% [95% CI, 5.2% to 7.6%] and 5.7% [CI, 5.0% to 6.6%], respectively) and lowest in the South American group (2.4% [CI, 1.7% to 3.5%]). Differences were attenuated with adjustment for lifestyle and clinical factors. During the pandemic, 2-year cumulative mortality risks adjusted for age and sex ranged from 1.1% (CI, 0.6% to 2.0%; South American) to 2.0% (CI, 1.4% to 3.0%; Central American); CIs overlapped across groups. With adjustment for lifestyle factors, 2-year cumulative mortality risks were highest in persons of Central American and Mexican backgrounds and lowest among those of Puerto Rican and Cuban backgrounds. LIMITATION: Lack of data on race and baseline citizenship status; correlation between Hispanic/Latino background and site. CONCLUSION: Differences in prepandemic mortality risks across Hispanic/Latino groups were explained by lifestyle and clinical factors. Mortality patterns changed during the pandemic, with higher risks in persons of Central American and Mexican backgrounds than in those of Puerto Rican and Cuban backgrounds. PRIMARY FUNDING SOURCE: National Institutes of Health.

Glycated Albumin and Adverse Clinical Outcomes in Patients With CKD: A Prospective Cohort Study.

RATIONALE & OBJECTIVE: Hemoglobin A1c (HbA1c) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,110 participants with CKD from the Chronic Renal Insufficiency Cohort study. EXPOSURE: Baseline GA levels. OUTCOME: Incident end-stage kidney disease (ESKD), cardiovascular disease (CVD) events, and all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards regression. RESULTS: Participant characteristics included mean age 59.0±10.8 SD years; 1,357 (43.6%) female; and 1,550 (49.8%) with diabetes. The median GA was 18.7% (IQR, 15.8%-23.3%). During an average 7.9-year follow-up, there were 980 ESKD events, 968 CVD events, and 1,084 deaths. Higher GA levels were associated with greater risks of all outcomes, regardless of diabetes status: hazard ratios for ESKD, CVD, and death among participants with the highest quartile compared with quartile 2 (reference) were 1.42 (95% CI, 1.19-1.69), 1.67 (95% CI, 1.39-2.01), and 1.63 (95% CI, 1.37-1.94), respectively. The associations with CVD and death appeared J-shaped, with increased risk also seen at the lowest GA levels. Among patients with coexisting CKD and diabetes, the associations of GA with outcomes remained significant even after adjusting for HbA1c. For each outcome, we observed a significant increase in the fraction of new prognostic information when both GA and HbA1c were added to models. LIMITATIONS: Lack of longitudinal GA measurements; and HbA1c measurements were largely unavailable in participants without diabetes. CONCLUSIONS: Among patients with CKD, GA levels were independently associated with risks of ESKD, CVD, and mortality, regardless of diabetes status. GA added prognostic value to HbA1c among patients with coexisting CKD and diabetes. PLAIN-LANGUAGE SUMMARY: Hemoglobin A1c (HbA1c) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown. In this cohort study of 3,110 individuals with non-dialysis-dependent CKD, GA levels were independently associated with risks of end-stage kidney disease, cardiovascular disease (CVD), and mortality. The associations with CVD and mortality appeared to be J-shaped. Among patients with coexisting CKD and diabetes, GA added prognostic value to HbA1c. Thus, GA may be a valuable complementary test to HbA1c in patients with CKD.

Prevalence of infertility and pregnancy loss among individuals with kidney disease in the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Hispanic/Latino individuals are less likely to receive optimal treatment for chronic kidney disease than non-Hispanic whites. This may be particularly detrimental for women of reproductive age as chronic kidney disease increases risk for infertility, menstrual irregularities, and pregnancy loss. While these maternal outcomes have been associated with advanced chronic kidney disease, their occurrence in early chronic kidney disease is unclear. OBJECTIVES/DESIGN: Using baseline (2008-2011) and second study visit (2014-2017) data from the Hispanic Community Health Study/Study of Latinos, we retrospectively assessed the prevalence of chronic kidney disease as well as the association between chronic kidney disease and self-reported infertility, cessation of menses, hysterectomy, and nonviable pregnancy loss (experienced at less than 24 weeks gestation) in women of reproductive age (18-45 years). METHODS: Multivariable survey logistic regression analyses determined the unadjusted and multivariable-adjusted prevalence odds ratios with 95% confidence intervals between chronic kidney disease and the separate outcomes. RESULTS: Among 2589 Hispanic/Latino women included (mean age = 31.4 years), 4.6% were considered to have chronic kidney disease. In adjusted analyses, women with chronic kidney disease did not have a significantly increased odds of infertility (odds ratio = 1.02, 95% confidence interval = 0.42-2.49), cessation of menses (odds ratio = 1.25, 95% confidence interval = 0.52-3.04), or hysterectomy (odds ratio = 1.17, 95% confidence interval = 0.61-2.25) compared to those without chronic kidney disease. In those with chronic kidney disease, the adjusted odds of a nonviable pregnancy loss occurring after baseline visit were increased (odds ratio = 2.11, 95% confidence interval = 0.63-7.02) but not statistically significance. CONCLUSION: The presence of early stage chronic kidney disease did not confer a significant risk of infertility, cessation of menses, or nonviable pregnancy loss.

The Hispanic Community Health Study/Study of Latinos is a population-based study of over 16,000 Hispanic/Latino individuals throughout the United States. Within this cohort, we assessed the prevalence of chronic kidney disease in women of reproductive age (18­45 years old) and the associations between kidney disease and infertility, cessation of menses, and nonviable pregnancy loss (loss occurring before the 24th week of pregnancy). We found that kidney disease affected 1 in 20 women of reproductive age and those with kidney disease were more likely to have obesity, diabetes, and hypertension. Compared to those without kidney disease, the presence of kidney disease did not increase risk of infertility, cessation of menses, or nonviable pregnancy loss.

Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10-8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.

Factors Associated With Non-vaccination for Influenza Among Patients With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Vaccination for influenza is strongly recommended for people with chronic kidney disease (CKD) due to their immunocompromised state. Identifying risk factors for not receiving an influenza vaccine (non-vaccination) could inform strategies for improving vaccine uptake in this high-risk population. STUDY DESIGN: Longitudinal observational study. SETTING & PARTICIPANTS: 3,692 Chronic Renal Insufficiency Cohort Study (CRIC) participants. EXPOSURE: Demographic factors, social determinants of health, clinical conditions, and health behaviors. OUTCOME: Influenza non-vaccination, which was assessed based on a receipt of influenza vaccine ascertained during annual clinic visits in a subset of participants who were under nephrology care. ANALYTICAL APPROACH: Mixed-effects Poisson models to estimate adjusted prevalence ratios (APRs). RESULTS: Between 2009 and 2020, the pooled mean vaccine uptake was 72% (mean age, 66 years; 44% female; 44% Black race). In multivariable models, factors significantly associated with influenza non-vaccination were younger age (APR, 2.16 [95% CI, 1.85-2.52] for<50 vs≥75 years), Black race (APR, 1.58 [95% CI, 1.43-1.75] vs White race), lower education (APR, 1.20 [95% CI, 1.04-1.39 for less than high school vs college graduate]), lower annual household income (APR, 1.26 [95% CI, 1.06-1.49] for <$20,000 vs >$100,000), formerly married status (APR, 1.22 [95% CI, 1.09-1.35] vs currently married), and nonemployed status (APR, 1.13 [95% CI, 1.02-1.24] vs employed). In contrast, participants with diabetes (APR, 0.80 [95% CI, 0.73-0.87] vs no diabetes), chronic obstructive pulmonary disease (COPD) (APR, 0.80 [95% CI, 0.70-0.92] vs no COPD), end-stage kidney disease (APR, 0.64 [0.56 to 0.76] vs estimated glomerular filtration rate≥60mL/min/1.73m2), frailty (APR, 0.86 [95% CI, 0.74-0.99] vs no frailty), and ideal physical activity (APR, 0.90 [95% CI, 0.82-0.99] vs. physically inactive) were less likely to have non-vaccination status. LIMITATIONS: Possible residual confounding. CONCLUSIONS: Among adults with CKD receiving nephrology care, younger adults, Black individuals, and those with adverse social determinants of health were more likely to have the influenza non-vaccination status. Strategies are needed to address these disparities and reduce barriers to vaccination. PLAIN-LANGUAGE SUMMARY: Identifying risk factors for not receiving an influenza vaccine ("non-vaccination") in people living with kidney disease, who are at risk of influenza and its complications, could inform strategies for improving vaccine uptake. In this study, we examined whether demographic factors, social determinants of health, and clinical conditions were linked to the status of not receiving an influenza vaccine among people living with kidney disease and receiving nephrology care. We found that younger adults, Black individuals, and those with adverse social determinants of health were more likely to not receive the influenza vaccine. These findings suggest the need for strategies to address these disparities and reduce barriers to vaccination in people living with kidney disease.

Frailty and Cardiovascular Outcomes in Adults With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes in adults with kidney failure requiring dialysis. However, this relationship has not been thoroughly evaluated among those with non-dialysis-dependent CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2,539 adults in the Chronic Renal Insufficiency Cohort Study. EXPOSURE: Frailty status assessed using 5 criteria: slow gait speed, muscle weakness, low physical activity, exhaustion, and unintentional weight loss. OUTCOME: Atherosclerotic events, incident heart failure, all-cause death, and cardiovascular death. ANALYTICAL APPROACH: Cause-specific hazards models. RESULTS: At study entry, the participants' mean age was 62 years, 46% were female, the mean estimated glomerular filtration rate was 45.4mL/min/1.73m2, and the median urine protein was 0.2mg/day. Frailty status was as follows: 12% frail, 51% prefrail, and 37% nonfrail. Over a median follow-up of 11.4 years, there were 393 atherosclerotic events, 413 heart failure events, 497 deaths, and 132 cardiovascular deaths. In multivariable regression analyses, compared with nonfrailty, both frailty and prefrailty status were each associated with higher risk of an atherosclerotic event (HR, 2.03 [95% CI, 1.41-2.91] and 1.77 [95% CI, 1.35-2.31], respectively) and incident heart failure (HR, 2.22 [95% CI, 1.59-3.10] and 1.39 [95% CI, 1.07-1.82], respectively), as well as higher risk of all-cause death (HR, 2.52 [95% CI, 1.84-3.45] and 1.76 [95% CI, 1.37-2.24], respectively) and cardiovascular death (HR, 3.01 [95% CI, 1.62-5.62] and 1.78 [95% 1.06-2.99], respectively). LIMITATIONS: Self-report of aspects of the frailty assessment and comorbidities, which may have led to bias in some estimates. CONCLUSIONS: In adults with CKD, frailty status was associated with higher risk of cardiovascular events and mortality. Future studies are needed to evaluate the impact of interventions to reduce frailty on cardiovascular outcomes in this population. PLAIN-LANGUAGE SUMMARY: Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes. We sought to evaluate the association of frailty status with cardiovascular events and death in adults with CKD. Frailty was assessed according to the 5 phenotypic criteria detailed by Fried and colleagues. Among 2,539 participants in the CRIC Study, we found that 12% were frail, 51% were prefrail, and 37% were nonfrail. Frailty status was associated with an increased risk of atherosclerotic events, incident heart failure, and death.

Fibroblast Growth Factor 23 and Risk of Heart Failure Subtype: The CRIC (Chronic Renal Insufficiency Cohort) Study.

Rationale & Objective: Heart failure (HF) is an important cause of morbidity and mortality among individuals with chronic kidney disease (CKD). A large body of evidence from preclinical and clinical studies implicates excess levels of fibroblast growth factor 23 (FGF23) in HF pathogenesis in CKD. It remains unclear whether the relationship between elevated FGF23 levels and HF risk among individuals with CKD varies by HF subtype. Study Design: Prospective cohort study. Settings & Participants: A total of 3,502 participants were selected in the Chronic Renal Insufficiency Cohort study. Exposure: Baseline plasma FGF23. Outcomes: Incident HF by subtype and total rate of HF hospitalization. HF was categorized as HF with preserved ejection fraction (HFpEF, ejection fraction [EF] ≥ 50%), HF with reduced EF (HFrEF, EF < 50%) and HF with unknown EF (HFuEF). Analytical Approach: Multivariable-adjusted cause-specific Cox proportional hazards models were used to investigate associations between FGF23 and incident hospitalizations for HF by subtype. The Lunn-McNeil method was used to compare hazard ratios across HF subtypes. Poisson regression models were used to evaluate the total rate of HF. Results: During a median follow-up time of 10.8 years, 295 HFpEF, 242 HFrEF, and 156 HFuEF hospitalizations occurred. In multivariable-adjusted cause-specific Cox proportional hazards models, FGF23 was significantly associated with the incidence of HFpEF (HR, 1.41; 95% CI, 1.21-1.64), HFrEF (HR, 1.27; 95% CI, 1.05-1.53), and HFuEF (HR, 1.40; 95% CI, 1.13-1.73) per 1 standard deviation (SD) increase in the natural log of FGF23. The Lunn-McNeil method determined that the risk association was consistent across all subtypes. The rate ratio of total HF events increased with FGF23 quartile. In multivariable-adjusted models, compared with quartile 1, FGF23 quartile 4 had a rate ratio of 1.81 (95% CI, 1.28-2.57) for total HF events. Limitations: Self-report of HF hospitalizations and possible lack of an echocardiogram at time of hospitalization. Conclusions: In this large multicenter prospective cohort study, elevated FGF23 levels were associated with increased risks for all HF subtypes. Plain-Language Summary: Heart failure (HF) is a prominent cause of morbidity and mortality in individuals with chronic kidney disease (CKD). Identifying potential pathways in the development of HF is essential in developing therapies to prevent and treat HF. In a large cohort of individuals with CKD, the Chronic Renal Insufficiency Cohort (N = 3,502), baseline fibroblast growth factor-23 (FGF23), a hormone that regulates phosphorous, was evaluated in relation to the development of incident and recurrent HF with reduced, preserved, and unknown ejection fraction. In this large multicenter prospective cohort study, elevated FGF23 levels were associated with increased risk of all HF subtypes. These findings demonstrate the need for further research into FGF23 as a target in preventing the development of HF in individuals with CKD.

Proteomics of CKD progression in the chronic renal insufficiency cohort.

Progression of chronic kidney disease (CKD) portends myriad complications, including kidney failure. In this study, we analyze associations of 4638 plasma proteins among 3235 participants of the Chronic Renal Insufficiency Cohort Study with the primary outcome of 50% decline in estimated glomerular filtration rate or kidney failure over 10 years. We validate key findings in the Atherosclerosis Risk in the Communities study. We identify 100 circulating proteins that are associated with the primary outcome after multivariable adjustment, using a Bonferroni statistical threshold of significance. Individual protein associations and biological pathway analyses highlight the roles of bone morphogenetic proteins, ephrin signaling, and prothrombin activation. A 65-protein risk model for the primary outcome has excellent discrimination (C-statistic[95%CI] 0.862 [0.835, 0.889]), and 14/65 proteins are druggable targets. Potentially causal associations for five proteins, to our knowledge not previously reported, are supported by Mendelian randomization: EGFL9, LRP-11, MXRA7, IL-1 sRII and ILT-2. Modifiable protein risk markers can guide therapeutic drug development aimed at slowing CKD progression.

Effect of Intensive Blood Pressure Control on Kidney Outcomes: Long-Term Electronic Health Record-Based Post-Trial Follow-Up of SPRINT.

BACKGROUND: Intensive BP lowering in the Systolic Blood Pressure Intervention Trial (SPRINT) produced acute decreases in kidney function and higher risk for AKI. We evaluated the effect of intensive BP lowering on long-term changes in kidney function using trial and outpatient electronic health record (EHR) creatinine values. METHODS: SPRINT data were linked with EHR data from 49 (of 102) study sites. The primary outcome was the total slope of decline in eGFR for the intervention phase and the post-trial slope of decline during the observation phase using trial and outpatient EHR values. Secondary outcomes included a ≥30% decline in eGFR to <60 ml/min per 1.73 m 2 and a ≥50% decline in eGFR or kidney failure among participants with baseline eGFR ≥60 and <60 ml/min per 1.73 m 2 , respectively. RESULTS: EHR creatinine values were available for a median of 8.3 years for 3041 participants. The total slope of decline in eGFR during the intervention phase was -0.67 ml/min per 1.73 m 2 per year (95% confidence interval [CI], -0.79 to -0.56) in the standard treatment group and -0.96 ml/min per 1.73 m 2 per year (95% CI, -1.08 to -0.85) in the intensive treatment group ( P < 0.001). The slopes were not significantly different during the observation phase: -1.02 ml/min per 1.73 m 2 per year (95% CI, -1.24 to -0.81) in the standard group and -0.85 ml/min per 1.73 m 2 per year (95% CI, -1.07 to -0.64) in the intensive group. Among participants without CKD at baseline, intensive treatment was associated with higher risk of a ≥30% decline in eGFR during the intervention (hazard ratio, 3.27; 95% CI, 2.43 to 4.40), but not during the postintervention observation phase. In those with CKD at baseline, intensive treatment was associated with a higher hazard of eGFR decline only during the intervention phase (hazard ratio, 1.95; 95% CI, 1.03 to 3.70). CONCLUSIONS: Intensive BP lowering was associated with a steeper total slope of decline in eGFR and higher risk for kidney events during the intervention phase of the trial, but not during the postintervention observation phase.

Ideal Cardiovascular Health in Mexican Adults with CKD Living in Mexico City Versus Chicago.

Evidence suggests that Mexican adults living in Mexico have a more favorable cardiovascular risk profile than Mexican adults living in the U.S. However, this relationship has not been evaluated among patients with chronic kidney disease (CKD), which is a question of importance given the high risk for cardiovascular disease among patients with CKD. Using data from two ongoing observational cohort studies, we compared the prevalence of ideal cardiovascular health metrics (assessed by the American Heart Association "Life's Simple 7" criteria) in 309 Mexican adults with CKD living in Mexico City to 343 Mexican adults with CKD living in Chicago. Mexican adults with CKD living in Mexico City had a significantly higher prevalence of ideal body mass index (25 vs. 10%), diet (17 vs. 8%), total cholesterol (80 vs. 63%), blood pressure (43 vs. 25%), and fasting glucose (54 vs. 42%). Mexican adults with CKD living in both Mexico City and Chicago had low levels of cardiovascular health scores. Future work is needed to better understand the lower prevalence of ideal cardiovascular health metrics in Chicago as compared to Mexico City.

Risk for Chronic Kidney Disease Progression After Acute Kidney Injury: Findings From the Chronic Renal Insufficiency Cohort Study.

BACKGROUND: Prior studies associating acute kidney injury (AKI) with more rapid subsequent loss of kidney function had methodological limitations, including inadequate control for differences between patients who had AKI and those who did not. OBJECTIVE: To determine whether AKI is independently associated with subsequent kidney function trajectory among patients with chronic kidney disease (CKD). DESIGN: Multicenter prospective cohort study. SETTING: United States. PARTICIPANTS: Patients with CKD (n = 3150). MEASUREMENTS: Hospitalized AKI was defined by a 50% or greater increase in inpatient serum creatinine (SCr) level from nadir to peak. Kidney function trajectory was assessed using estimated glomerular filtration rate (eGFR) based on SCr level (eGFRcr) or cystatin C level (eGFRcys) measured at annual study visits. RESULTS: During a median follow-up of 3.9 years, 433 participants had at least 1 AKI episode. Most episodes (92%) had stage 1 or 2 severity. There were decreases in eGFRcr (-2.30 [95% CI, -3.70 to -0.86] mL/min/1.73 m2) and eGFRcys (-3.61 [CI, -6.39 to -0.82] mL/min/1.73 m2) after AKI. However, in fully adjusted models, the decreases were attenuated to -0.38 (CI, -1.35 to 0.59) mL/min/1.73 m2 for eGFRcr and -0.15 (CI, -2.16 to 1.86) mL/min/1.73 m2 for eGFRcys, and the CI bounds included the possibility of no effect. Estimates of changes in eGFR slope after AKI determined by either SCr level (0.04 [CI, -0.30 to 0.38] mL/min/1.73 m2 per year) or cystatin C level (-0.56 [CI, -1.28 to 0.17] mL/min/1.73 m2 per year) also had CI bounds that included the possibility of no effect. LIMITATIONS: Few cases of severe AKI, no adjudication of AKI cause, and lack of information about nephrotoxic exposures after hospital discharge. CONCLUSION: After pre-AKI eGFR, proteinuria, and other covariables were accounted for, the association between mild to moderate AKI and worsening subsequent kidney function in patients with CKD was small. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

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.

The Relationship Between Sleep and Brain Function in Older Adults With Chronic Kidney Disease and Self-Identified Cognitive Impairment.

Older adults with chronic kidney disease (CKD) are at risk for cognitive impairment and sleep disturbances. The purpose of the current study was to investigate the relationship between sleep and brain structure/function in older adults with CKD and self-identified cognitive impairment. The sample (N = 37) had a mean age of 68 years (SD = 4.9 years), estimated glomerular filtration rate of 43.7 mL/min/1.73m2 (SD = 10.98), median sleep time of 7.4 hours, and was 70% female. Sleeping <7.4 hours, compared to ≥7.4 hours, was associated with better attention/information processing (ß = 11.46, 95% confidence interval [CI] [3.85, 19.06]) and better learning/memory (ß = 2.06, 95% CI [0.37, 3.75]). Better sleep efficiency was associated with better global cerebral blood flow (ß = 3.30, 95% CI [0.65, 5.95]). Longer awake length after sleep onset was associated with worse fractional anisotropy of the cingulum (ß = -0.01, 95% CI [-0.02, -0.003]). Sleep duration and continuity may be related to brain function in older adults with CKD and self-identified cognitive impairment. [Journal of Gerontological Nursing, 49(7), 31-39.].

Community-level socioeconomic distress is associated with nutritional status in adults with sickle cell anemia.

Sickle cell anemia (SCA) negatively impacts the ability to achieve educational and occupational goals increasing vulnerability to socioeconomic challenges. In a cross-sectional analysis of 332 SCA adults, we investigated whether the distressed community index (DCI) was associated with SCA-related complications and nutritional status. More patients with higher DCI had Medicaid insurance. A higher DCI was independently associated with tobacco use and lower body mass index, serum albumin, and vitamin D 25-OH levels after adjusting for insurance status but was not associated with SCA-related complications. Future studies investigating access to healthy foods may help improve health equity in patients with SCA.

Effects of epigenetic age acceleration on kidney function: a Mendelian randomization study.

BACKGROUND: Previous studies have reported cross-sectional associations between measures of epigenetic age acceleration (EAA) and kidney function phenotypes. However, the temporal and potentially causal relationships between these variables remain unclear. We conducted a bidirectional two-sample Mendelian randomization study of EAA and kidney function. Genetic instruments for EAA and estimate glomerular filtration rate (eGFR) were identified from previous genome-wide association study (GWAS) meta-analyses of European-ancestry participants. Causal effects of EAA on kidney function and kidney function on EAA were assessed through summary-based Mendelian randomization utilizing data from the CKDGen GWAS meta-analysis of log-transformed estimated glomerular filtration rate (log-eGFR; n = 5,67,460) and GWAS meta-analyses of EAA (n = 34,710). An allele score-based Mendelian randomization leveraging individual-level data from UK Biobank participants (n = 4,33,462) further examined the effects of EAA on kidney function. RESULTS: Using summary-based Mendelian randomization, we found that each 5 year increase in intrinsic EAA (IEAA) and GrimAge acceleration (GrimAA) was associated with - 0.01 and - 0.02 unit decreases in log-eGFR, respectively (P = 0.02 and P = 0.09, respectively), findings which were strongly supported by allele-based Mendelian randomization study (both P < 0.001). Summary-based Mendelian randomization identified 24% increased odds of CKD with each 5-unit increase in IEAA (P = 0.05), with consistent findings observed in allele score-based analysis (P = 0.07). Reverse-direction Mendelian randomization identified potentially causal effects of decreased kidney function on HannumAge acceleration (HannumAA), GrimAA, and PhenoAge acceleration (PhenoAA), conferring 3.14, 1.99, and 2.88 year decreases in HanumAA, GrimAA, and PhenoAA, respectively (P = 0.003, 0.05, and 0.002, respectively) with each 1-unit increase in log-eGFR. CONCLUSION: This study supports bidirectional causal relationships between EAA and kidney function, pointing to potential prevention and therapeutic strategies.

Probing the Association between Acute Kidney Injury and Cardiovascular Outcomes.

BACKGROUND: Patients hospitalized with AKI have higher subsequent risks of heart failure, atherosclerotic cardiovascular events, and mortality than their counterparts without AKI, but these higher risks may be due to differences in prehospitalization patient characteristics, including the baseline level of estimated glomerular filtration rate (eGFR), the rate of prior eGFR decline, and the proteinuria level, rather than AKI itself. METHODS: Among 2177 adult participants in the Chronic Renal Insufficiency Cohort study who were hospitalized in 2013-2019, we compared subsequent risks of heart failure, atherosclerotic cardiovascular events, and mortality between those with serum creatinine-based AKI (495 patients) and those without AKI (1682 patients). We report both crude associations and associations sequentially adjusted for prehospitalization characteristics including eGFR, eGFR slope, and urine protein-creatinine ratio (UPCR). RESULTS: Compared with patients hospitalized without AKI, those with hospitalized AKI had lower eGFR prehospitalization (42 versus 49 ml/min per 1.73 m 2 ), faster chronic loss of eGFR prehospitalization (-0.84 versus -0.51 ml/min per 1.73 m 2 per year), and more proteinuria prehospitalization (UPCR 0.28 versus 0.16 g/g); they also had higher prehospitalization systolic BP (130 versus 127 mm Hg; P < 0.01 for all comparisons). Adjustment for prehospitalization patient characteristics attenuated associations between AKI and all three outcomes, but AKI remained an independent risk factor. Attenuation of risk was similar after adjustment for absolute eGFR, eGFR slope, or proteinuria, individually or in combination. CONCLUSIONS: Prehospitalization variables including eGFR, eGFR slope, and proteinuria confounded associations between AKI and adverse cardiovascular outcomes, but these associations remained significant after adjusting for prehospitalization variables.