Associations between long-term exposure to air pollution and kidney function utilizing electronic healthcare records: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) affects more than 38 million people in the United States, predominantly those over 65 years of age. While CKD etiology is complex, recent research suggests associations with environmental exposures. METHODS: Our primary objective is to examine creatinine-based estimated glomerular filtration rate (eGFRcr) and diagnosis of CKD and potential associations with fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) using a random sample of North Carolina electronic healthcare records (EHRs) from 2004 to 2016. We estimated eGFRcr using the serum creatinine-based 2021 CKD-EPI equation. PM2.5 and NO2 data come from a hybrid model using 1 km2 grids and O3 data from 12 km2 CMAQ grids. Exposure concentrations were 1-year averages. We used linear mixed models to estimate eGFRcr per IQR increase of pollutants. We used multiple logistic regression to estimate associations between pollutants and first appearance of CKD. We adjusted for patient sex, race, age, comorbidities, temporality, and 2010 census block group variables. RESULTS: We found 44,872 serum creatinine measurements among 7,722 patients. An IQR increase in PM2.5 was associated with a 1.63 mL/min/1.73m2 (95% CI: -1.96, -1.31) reduction in eGFRcr, with O3 and NO2 showing positive associations. There were 1,015 patients identified with CKD through e-phenotyping and ICD codes. None of the environmental exposures were positively associated with a first-time measure of eGFRcr < 60 mL/min/1.73m2. NO2 was inversely associated with a first-time diagnosis of CKD with aOR of 0.77 (95% CI: 0.66, 0.90). CONCLUSIONS: One-year average PM2.5 was associated with reduced eGFRcr, while O3 and NO2 were inversely associated. Neither PM2.5 or O3 were associated with a first-time identification of CKD, NO2 was inversely associated. We recommend future research examining the relationship between air pollution and impaired renal function.

Effectiveness of an Advance Care Planning Intervention in Adults Receiving Dialysis and Their Families: A Cluster Randomized Clinical Trial.

Importance: Evidence of effectiveness of advance care planning (ACP) strategies for patients receiving dialysis and their families is needed. Objectives: To test the effectiveness of an ACP intervention to prepare patients and their surrogates for end-of-life (EOL) decision-making and to improve surrogate bereavement outcomes. Design, Setting, and Participants: This cluster randomized clinical trial, An Effectiveness-Implementation Trial of SPIRIT (Sharing Patients' Illness Representations to Increase Trust) in ESRD, was conducted from December 2017 to March 2023 and included 42 dialysis clinics in 5 US states (Georgia, New Mexico, North Carolina, Pennsylvania, and Virginia) randomized to provide intervention or usual care. Recruitment was from February 15, 2018, to January 31, 2022, and patient-surrogate dyads were followed up for 21 months (until January 17, 2023) or until patient death. Intervention: Each clinic selected 1 or 2 health care workers (eg, nurse practitioner, registered nurse, or social worker) to conduct 45- to 60-minute ACP discussions with dyads in the clinic or remotely. After March 13, 2020 (commencement of the COVID-19 emergency declaration), all discussions were conducted remotely. An ACP summary was placed in patients' medical records. Main Outcomes and Measures: The primary, 2-week preparedness outcomes were dyad congruence on EOL goals of care, patient decisional conflict, surrogate decision-making confidence, and a composite of dyad congruence and surrogate decision-making confidence. Secondary bereavement outcomes were anxiety, depression, and posttraumatic distress 3 months after patient death. To adjust for COVID-19 pandemic effects on bereavement outcomes, a variable to indicate the timing of baseline and 3-month assessment relative to the COVID-19 emergency declaration was created. Results: Of the 426 dyads enrolled, 231 were in the intervention clinics, and 195 were in the control clinics. Among all dyads, the mean (SD) patient age was 61.9 (12.7) years, and the mean (SD) surrogate age was 53.7 (15.4) years. At 2 weeks, after adjusting for baseline values, dyad congruence (odds ratio [OR], 1.61; 95% CI, 1.12-2.31; P = .001), decisional conflict scores (ß, -0.10; 95% CI, -0.13 to -0.07; P < .001), and the composite (OR, 1.57; 95% CI, 1.06-2.34; P = .03) were higher in the intervention group than in the control group. Surrogate decision-making confidence was similar between groups (ß, 0.06; 95% CI, -0.01 to 0.13; P = .12). Among 77 bereaved surrogates, after adjusting for baseline values and assessment timing, intervention group anxiety was lower than control group anxiety (ß, -1.55; 95% CI, -3.08 to -0.01; P = .05); however, depression (ß, -0.18; 95% CI, -2.09 to 1.73; P = .84) and posttraumatic distress (ß, -0.96; 95% CI, -7.39 to 5.46; P = .75) were similar. Conclusions and Relevance: In this randomized clinical trial, the ACP intervention implemented by health care workers at dialysis centers improved preparation for EOL decision-making but showed mixed effectiveness on bereavement outcomes. The ACP intervention implemented in dialysis centers may be an effective strategy to the dyad preparation for end-of-life care as opposed to the current focus on advance directives. Trial Registration: ClinicalTrials.gov Identifier: NCT03138564.

Comparative Effect of Loop Diuretic Prescription on Mortality and Heart Failure Readmission.

Loop diuretics are a standard pharmacologic therapy in heart failure (HF) management. Although furosemide is most frequently used, torsemide and bumetanide are increasingly prescribed in clinical practice, possibly because of superior bioavailability. Few real-world comparative effectiveness studies have examined outcomes across all 3 loop diuretics. The study goal was to compare the effects of loop diuretic prescribing at HF hospitalization discharge on mortality and HF readmission. We identified patients in Medicare claims data initiating furosemide, torsemide, or bumetanide after an index HF hospitalization from 2007 to 2017. We estimated 6-month risks of all-cause mortality and a composite outcome (HF readmission or all-cause mortality) using inverse probability of treatment weighting to adjust for relevant confounders. We identified 62,632 furosemide, 1,720 torsemide, and 2,389 bumetanide initiators. The 6-month adjusted all-cause mortality risk was lowest for torsemide (13.2%), followed by furosemide (14.5%) and bumetanide (15.6%). The 6-month composite outcome risk was 21.4% for torsemide, 24.7% for furosemide, and 24.9% for bumetanide. Compared with furosemide, the 6-month all-cause mortality risk was 1.3% (95% confidence interval [CI]: -3.7, 1.0) lower for torsemide and 1.0% (95% CI: -1.2, 3.2) higher for bumetanide, and the 6-month composite outcome risk was 3.3% (95% CI: -6.3, -0.3) lower for torsemide and 0.2% (95% CI: -2.5, 2.9) higher for bumetanide. In conclusion, the findings suggested that the first prescribed loop diuretic following HF hospitalization is associated with clinically important differences in morbidity in older patients receiving torsemide, bumetanide, or furosemide. These differences were consistent for the effect of all-cause mortality alone, but were not statistically significant.

Associations of Air Pollution and Serum Biomarker Abnormalities in Individuals with Hemodialysis-Dependent Kidney Failure.

BACKGROUND: Ambient particles with a median aerodynamic diameter of <2.5 µm (PM2.5) is a ubiquitous air pollutant with established adverse health consequences. While postulated to promote a systemic inflammatory response, limited studies have demonstrated changes in serum biomarkers related to PM2.5 exposure. We aim to examine associations between short-term PM2.5 exposure and commonly measured biomarkers known to be affected by inflammation among patients receiving maintenance in-center hemodialysis. METHODS: We conducted a retrospective open cohort study from January 1, 2008, to December 31, 2014. Adult hemodialysis patients were identified from the United States Renal Data System and linked at the patient level to laboratory data from a large dialysis organization. Daily ambient PM2.5 was estimated on a 1-km grid and assigned to cohort patients based on the ZIP codes of dialysis clinics. Serum albumin, serum ferritin, transferrin saturation (TSAT), and serum hemoglobin were ascertained from the dialysis provider organization database. Mixed-effect models were used to assess the changes in biomarker levels associated with PM2.5 exposure. RESULTS: The final cohort included 173,697 hemodialysis patients. Overall, the daily ZIP-level ambient PM2.5 averages were 8.4-8.5 µg/m3. A 10-µg/m3 increase in same-day ambient PM2.5 exposure was associated with higher relative risks of lower albumin (relative risk [RR], 1.01; 95% confidence interval [95% CI], 1.01 to 1.02) and lower hemoglobin (RR, 1.02; 95% CI, 1.01 to 1.03). Associations of same-day ambient PM2.5 exposure and higher ferritin and lower TSAT did not reach statistical significance. CONCLUSIONS: Short-term PM2.5 exposure was associated with lower serum hemoglobin and albumin among patients receiving in-center hemodialysis. These findings lend support to the role of inflammation in PM2.5 exposure-outcome associations.

Association Between Long-term Ambient PM2.5 Exposure and Cardiovascular Outcomes Among US Hemodialysis Patients.

RATIONALE & OBJECTIVE: Ambient PM2.5 (particulate matter with a diameter of 2.5 microns) is a ubiquitous air pollutant with established adverse cardiovascular (CV) effects. However, quantitative estimates of the association between PM2.5 exposure and CV outcomes in the setting of kidney disease are limited. This study assessed the association of long-term PM2.5 exposure with CV events and cardiovascular disease (CVD)-specific mortality among patients receiving maintenance in-center hemodialysis (HD). STUDY DESIGN: Retrospective cohort study. SETTINGS & PARTICIPANTS: 314,079 adult kidney failure patients initiating HD between 2011 and 2016 identified from the US Renal Data System. EXPOSURE: Estimated daily ZIP code-level PM2.5 concentrations were used to calculate each participant's annual average PM2.5 exposure based on the dialysis clinics visited during the 365 days before the outcome. OUTCOME: CV event and CVD-specific mortality were ascertained based on ICD-9/ICD-10 diagnostic codes and recorded cause of death from Centers for Medicare & Medicaid Services form 2746. ANALYTICAL APPROACH: Discrete time hazards models were used to estimate hazards ratios per 1 µg/m3 greater annual average PM2.5, adjusting for temperature, humidity, day of the week, season, age at baseline, race, employment status, and geographic region. Effect measure modification was assessed for age, sex, race, and baseline comorbidities. RESULTS: Each 1 µg/m3 greater annual average PM2.5 was associated with a greater rate of CV events (HR, 1.02 [95% CI, 1.01-1.02]) and CVD-specific mortality (HR, 1.02 [95% CI, 1.02-1.03]). The association was more pronounced for people who initiated dialysis at an older age, had chronic obstructive pulmonary disease (COPD) at baseline, or were Asian. Evidence of effect modification was also observed across strata of race, and other baseline comorbidities. LIMITATIONS: Potential exposure misclassification and unmeasured confounding. CONCLUSIONS: Long-term ambient PM2.5 exposure was associated with CVD outcomes among patients receiving maintenance in-center HD. Stronger associations between long-term PM2.5 exposure and adverse effects were observed among patients who were of advanced age, had COPD, or were Asian. PLAIN-LANGUAGE SUMMARY: Long-term exposure to air pollution, also called PM2.5, has been linked to adverse cardiovascular outcomes. However, little is known about the association of PM2.5 and outcomes among patients receiving dialysis, who are individuals with high cardiovascular disease burdens. We conducted an epidemiological study to assess the association between the annual PM2.5 exposure and cardiovascular events and death among patients receiving regular outpatient hemodialysis in the United States between 2011 and 2016. We found a higher risk of heart attacks, strokes, and related events in patients exposed to higher levels of air pollution. Stronger associations between air pollution and adverse health events were observed among patients who were older at the start of dialysis, had chronic obstructive pulmonary disease, or were Asian. These findings bolster the evidence base linking air pollution and adverse health outcomes and may inform policy makers and clinicians.

Keys to Driving Implementation of the New Kidney Care Models.

Contemporary nephrology practice is heavily weighted toward in-center hemodialysis, reflective of decisions on infrastructure and personnel in response to decades of policy. The Advancing American Kidney Health initiative seeks to transform care for patients and providers. Under the initiative's framework, the Center for Medicare and Medicaid Innovation has launched two new care models that align patient choice with provider incentives. The mandatory ESRD Treatment Choices model requires participation by all nephrology practices in designated Hospital Referral Regions, randomly selecting 30% of all Hospital Referral Regions across the United States for participation, with the remaining Hospital Referral Regions serving as controls. The voluntary Kidney Care Choices model offers alternative payment programs open to nephrology practices throughout the country. To help organize implementation of the models, we developed Driver Diagrams that serve as blueprints to identify structures, processes, and norms and generate intervention concepts. We focused on two goals that are directly applicable to nephrology practices and central to the incentive structure of the ESRD Treatment Choices and Kidney Care Choices: (1) increasing utilization of home dialysis, and (2) increasing the number of kidney transplants. Several recurring themes became apparent with implementation. Multiple stakeholders from assorted backgrounds are needed. Communication with primary care providers will facilitate timely referrals, education, and comanagement. Nephrology providers (nephrologists, nursing, dialysis organizations, others) must lead implementation. Patient engagement at nearly every step will help achieve the aims of the models. Advocacy with federal and state regulatory agencies will be crucial to expanding home dialysis and transplantation access. Although the models hold promise to improve choices and outcomes for many patients, we must be vigilant that they not do reinforce existing disparities in health care or widen known racial, socioeconomic, or geographic gaps. The Advancing American Kidney Health initiative has the potential to usher in a new era of value-based care for nephrology.

Effects of short-term ambient PM2.5 exposure on cardiovascular disease incidence and mortality among U.S. hemodialysis patients: a retrospective cohort study.

BACKGROUND: Ambient PM2.5 is a ubiquitous air pollutant with demonstrated adverse health impacts in population. Hemodialysis patients are a highly vulnerable population and may be particularly susceptible to the effects of PM2.5 exposure. This study examines associations between short-term PM2.5 exposure and cardiovascular disease (CVD) and mortality among patients receiving maintenance in-center hemodialysis. METHODS: Using the United State Renal Data System (USRDS) registry, we enumerated a cohort of all US adult kidney failure patients who initiated in-center hemodialysis between 1/1/2011 and 12/31/2016. Daily ambient PM2.5 exposure estimates were assigned to cohort members based on the ZIP code of the dialysis clinic. CVD incidence and mortality were ascertained through 2016 based on USRDS records. Discrete time hazards regression was used to estimate the association between lagged PM2.5 exposure and CVD incidence, CVD-specific mortality, and all-cause mortality 1 t adjusting for temperature, humidity, day of the week, season, age at baseline, race, employment status, and geographic region. Effect measure modification was assessed for age, sex, race, and comorbidities. RESULTS: Among 314,079 hemodialysis patients, a 10 µg/m3 increase in the average lag 0-1 daily PM2.5 exposure was associated with CVD incidence (HR: 1.03 (95% CI: 1.02, 1.04)), CVD mortality (1.05 (95% CI: 1.03, 1.08)), and all-cause mortality (1.04 (95% CI: 1.03, 1.06)). The association was larger for people who initiated dialysis at an older age, while minimal evidence of effect modification was observed across levels of sex, race, or baseline comorbidities. CONCLUSIONS: Short-term ambient PM2.5 exposure was positively associated with incident CVD events and mortality among patients receiving in-center hemodialysis. Older patients appeared to be more susceptible to PM2.5-associated CVD events than younger hemodialysis patients.

Environmental Exposures and Kidney Disease.

Accumulating evidence underscores the large role played by the environment in the health of communities and individuals. We review the currently known contribution of environmental exposures and pollutants on kidney disease and its associated morbidity. We review air pollutants, such as particulate matter; water pollutants, such as trace elements, per- and polyfluoroalkyl substances, and pesticides; and extreme weather events and natural disasters. We also discuss gaps in the evidence that presently relies heavily on observational studies and animal models, and propose using recently developed analytic methods to help bridge the gaps. With the expected increase in the intensity and frequency of many environmental exposures in the decades to come, an improved understanding of their potential effect on kidney disease is crucial to mitigate potential morbidity and mortality.

Performance of Diabetes and Kidney Disease Screening Scores in Contemporary United States and Korean Populations.

BACKGROUND: Risk assessment tools have been actively studied, and they summarize key predictors with relative weights/importance for a disease. Currently, standardized screening scores for type 2 diabetes mellitus (DM) and chronic kidney disease (CKD)-two key global health problems-are available in United States and Korea. We aimed to compare and evaluate screening scores for DM (or combined with prediabetes) and CKD, and assess the risk in contemporary United States and Korean populations. METHODS: Four (2×2) models were evaluated in the United States-National Health and Nutrition Examination Survey (NHANES 2015-2018) and Korea-NHANES (2016-2018)-8,928 and 16,209 adults. Weighted statistics were used to describe population characteristics. We used logistic regression for predictors in the models to assess associations with study outcomes (undiagnosed DM and CKD) and diagnostic measures for temporal and cross-validation. RESULTS: Korean adult population (mean age 47.5 years) appeared to be healthier than United States counterpart, in terms of DM and CKD risks and associated factors, with exceptions of undiagnosed DM, prediabetes and prehypertension. Models performed well in own country and external populations regarding predictor-outcome association and discrimination. Risk tests (high vs. low) showed area under the curve >0.75, sensitivity >84%, specificity >45%, positive predictive value >8%, and negative predictive value >99%. Discrimination was better for DM, compared to the combined outcome of DM and prediabetes, and excellent for CKD due to age. CONCLUSION: Four easy-to-use screening scores for DM and CKD are well-validated in contemporary United States and Korean populations. Prevention of DM and CKD may serve as first-step in public health, with these self-assessment tools as basic tools to help health education and disparity.

A Person-Centered Interdisciplinary Plan-of-Care Program for Dialysis: Implementation and Preliminary Testing.

RATIONALE & OBJECTIVE: Despite growing interest in individualizing care, routine dialysis processes, including the interdisciplinary plan of care, often fail to account for patient-identified priorities. To better align dialysis care with patient priorities and improve care planning experiences, we implemented a person-centered care plan program at a single clinic. We also sought to gain insight into key implementation considerations and areas for program improvement. STUDY DESIGN: 6-month quality improvement project with research substudy. SETTING & PARTICIPANTS: 49 hemodialysis patients and 14 care team members at a North Carolina dialysis clinic. QUALITY IMPROVEMENT ACTIVITIES: Implementation of My Dialysis Plan, a person-centered care plan program. OUTCOMES: Participant perspectives and care plan meeting characteristics (quality improvement); pre- to postprogram change in patient-reported autonomy support, patient-centeredness of care, and dialysis care individualization (research). ANALYTICAL APPROACH: We used the Consolidated Framework for Implementation Research to guide implementation and evaluation. We conducted pre-, intra-, and post-project interviews with clinic stakeholders (patients, clinic personnel, and medical providers) to identify implementation barriers, facilitators, and perceptions. We compared pre- and post-project care plan meeting content and patient-reported outcome survey scores. RESULTS: We conducted 54 care plans with 49 patients. Overall, care teams successfully used My Dialysis Plan to elicit and link patient priorities to actionable aspects of dialysis care. Participants identified interdisciplinary team commitment, accountability, and the structured yet flexible meeting approach as key implementation elements. Throughout the project, stakeholder input guided program modifications (eg, implementation practices and resources) to better meet clinic needs, but follow-up on care plan-identified action items remained challenging. Among the 28 substudy participants, there was no difference in pre- to post-project patient-reported outcome survey scores. LIMITATIONS: Single clinic implementation. CONCLUSIONS: My Dialysis Plan has the potential to enhance dialysis care individualization and care plan experiences. Evaluation of program impact on patient-reported and clinical outcomes is needed.

Controversies in optimal anemia management: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference.

In chronic kidney disease, anemia and disordered iron homeostasis are prevalent and associated with significant adverse consequences. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) issued an anemia guideline for managing the diagnosis, evaluation, and treatment of anemia in chronic kidney disease. Since then, new data have accrued from basic research, epidemiological studies, and randomized trials that warrant a re-examination of previous recommendations. Therefore, in 2019, KDIGO decided to convene 2 Controversies Conferences to review the latest evidence, explore new and ongoing controversies, assess change implications for the current KDIGO anemia guideline, and propose a research agenda. The first conference, described here, focused mainly on iron-related issues, including the contribution of disordered iron homeostasis to the anemia of chronic kidney disease, diagnostic challenges, available and emerging iron therapies, treatment targets, and patient outcomes. The second conference will discuss issues more specifically related to erythropoiesis-stimulating agents, including epoetins, and hypoxia-inducible factor-prolyl hydroxylase inhibitors. Here we provide a concise overview of the consensus points and controversies resulting from the first conference and prioritize key questions that need to be answered by future research.

Association of Sickle Cell Trait With Incidence of Coronary Heart Disease Among African American Individuals.

Importance: The incidence of and mortality from coronary heart disease (CHD) are substantially higher among African American individuals compared with non-Hispanic White individuals, even after adjusting for traditional factors associated with CHD. The unexplained excess risk might be due to genetic factors related to African ancestry that are associated with a higher risk of CHD, such as the heterozygous state for the sickle cell variant or sickle cell trait (SCT). Objective: To evaluate whether there is an association between SCT and the incidence of myocardial infarction (MI) or composite CHD outcomes in African American individuals. Design, Setting, and Participants: This cohort study included 5 large, prospective, population-based cohorts of African American individuals in the Women's Health Initiative (WHI) study, the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, the Multi-Ethnic Study of Atherosclerosis (MESA), the Jackson Heart Study (JHS), and the Atherosclerosis Risk in Communities (ARIC) study. The follow-up periods included in this study were 1993 and 1998 to 2014 for the WHI study, 2003 to 2014 for the REGARDS study, 2002 to 2016 for the MESA, 2002 to 2015 for the JHS, and 1987 to 2016 for the ARIC study. Data analysis began in October 2013 and was completed in October 2020. Exposures: Sickle cell trait status was evaluated by either direct genotyping or high-quality imputation of rs334 (the sickle cell variant). Participants with sickle cell disease and those with a history of CHD were excluded from the analyses. Main Outcomes and Measures: Incident MI, defined as adjudicated nonfatal or fatal MI, and incident CHD, defined as adjudicated nonfatal MI, fatal MI, coronary revascularization procedures, or death due to CHD. Cox proportional hazards regression models were used to estimate the hazard ratio for incident MI or CHD comparing SCT carriers with noncarriers. Models were adjusted for age, sex (except for the WHI study), study site or region of residence, hypertension status or systolic blood pressure, type 1 or 2 diabetes, serum high-density lipoprotein level, total cholesterol level, and global ancestry (estimated from principal components analysis). Results: A total of 23 197 African American men (29.8%) and women (70.2%) were included in the combined sample, of whom 1781 had SCT (7.7% prevalence). Mean (SD) ages at baseline were 61.2 (6.9) years in the WHI study (n = 5904), 64.0 (9.3) years in the REGARDS study (n = 10 714), 62.0 (10.0) years in the MESA (n = 1556), 50.3 (12.0) years in the JHS (n = 2175), and 53.2 (5.8) years in the ARIC study (n = 2848). There were no significant differences in the distribution of traditional factors associated with cardiovascular disease by SCT status within cohorts. A combined total of 1034 participants (76 with SCT) had incident MI, and 1714 (137 with SCT) had the composite CHD outcome. The meta-analyzed crude incidence rate of MI did not differ by SCT status and was 3.8 per 1000 person-years (95% CI, 3.3-4.5 per 1000 person-years) among those with SCT and 3.6 per 1000 person-years (95% CI, 2.7-5.1 per 1000 person-years) among those without SCT. For the composite CHD outcome, these rates were 7.3 per 1000 person-years (95% CI, 5.5-9.7 per 1000 person-years) among those with SCT and 6.0 per 1000 person-years (95% CI, 4.9-7.4 per 1000 person-years) among those without SCT. Meta-analysis of the 5 study results showed that SCT status was not significantly associated with MI (hazard ratio, 1.03; 95% CI, 0.81-1.32) or the composite CHD outcome (hazard ratio, 1.16; 95% CI, 0.92-1.47). Conclusions and Relevance: In this cohort study, there was not an association between SCT and increased risk of MI or CHD in African American individuals. These disorders may not be associated with sickle cell trait-related sudden death in this population.

Corrigendum to 'Association of sickle cell trait with measures of cognitive function and dementia in African Americans' eNeurologicalSci, Vol. 16 (2019), 100,201.

[This corrects the article DOI: 10.1016/j.ensci.2019.100201.].