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Objective: Women with gestational diabetes mellitus (GDM) maintain a higher risk for recurrent GDM and overt diabetes. Overt diabetes is a risk factor for development of chronic kidney disease (CKD), but GDM alone, without subsequent development of overt diabetes, may also pose a risk for CKD.Research Design and Methods: This cross-sectional analysis included Kidney Early Evaluation Program (KEEP) participants from 2000 to 2009. Patient characteristics and kidney function among three categories (GDM alone, overt diabetes, and no history of diabetes) were compared. The prevalence of microalbuminuria, macroalbuminuria, and CKD stages 1-2 and 3-5 was assessed using logistic regression.Results: Of 37,716 KEEP female participants, 571 (1.5%) had GDM alone and 12,100 (32.1%) had overt diabetes. Women with GDM had a higher rate of microalbuminuria but not macroalbuminuria than their nondiabetic peers (10.0 vs. 7.7%) that was substantially lower than the 13.6% prevalence in diabetic women. In multivariate analysis, women with GDM alone, compared with nondiabetic women, demonstrated increased odds of CKD stages 1-2 (multivariate odds ratio 1.54 [95% CI 1.16-2.05]) similar to the odds for women with overt diabetes (1.68 [1.55-1.82]). In stratified analyses, age, race, BMI, and hypertension modified the odds for CKD stages 1-2 but not CKD stages 3-5 among women with GDM.Conclusions: Women with GDM alone have a higher prevalence of microalbuminuria than women without any history of diabetes, translating to higher rates of CKD stages 1-2. These results suggest that GDM, even in the absence of subsequent overt diabetes, may increase the risk for future cardiovascular and kidney disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of mineralocorticoid receptor blockers (MRBs) in patients with chronic kidney disease is growing, but data for efficacy in decreasing proteinuria are limited by a relative paucity of studies, many of which are small and uncontrolled. STUDY DESIGN: We performed a systematic review using the MEDLINE database (inception to November 1, 2006), abstracts from national meetings, and selected reference lists. SETTING & POPULATION: Adult patients with chronic kidney disease and proteinuria. SELECTION CRITERIA FOR STUDIES: English-language studies investigating the use of MRBs added to long-term angiotensin-converting enzyme (ACE)-inhibitor and/or angiotensin receptor blocker (ARB) therapy in adult patients with proteinuric kidney disease. INTERVENTION: MRBs as additive therapy to conventional renin-angiotensin-aldosterone system blockade in patients with chronic kidney disease. OUTCOMES: Changes in proteinuria as the primary outcome; rates of hyperkalemia, changes in blood pressure, and changes in glomerular filtration rate as secondary outcomes. RESULTS: 15 studies met inclusion criteria for our review; 4 were parallel-group randomized controlled trials, 4 were crossover randomized controlled trials, 2 were pilot studies, and 5 were case series. When MRBs were added to ACE-inhibitor and/or ARB therapy, the reported proteinuria decreases from baseline ranged from 15% to 54%, with most estimates in the 30% to 40% range. Hyperkalemic events were significant in only 1 of 8 randomized controlled trials. MRB therapy was associated with statistically significant decreases in blood pressure and glomerular filtration rate in approximately 40% and 25% of included studies, respectively. LIMITATIONS: Reported results were insufficient for meta-analysis, with only 2 studies reporting sufficient data to calculate SEs of their published estimates. We were unable to locate studies that showed no effect of MRB treatment over placebo, raising concern for publication bias. CONCLUSIONS: Although data suggest that adding MRBs to ACE-inhibitor and/or ARB therapy yields significant decreases in proteinuria without adverse effects of hyperkalemia and impaired renal function, routine use of MRBs as additive therapy in patients with chronic kidney disease cannot be recommended yet. However, the findings of this review promote interesting hypotheses for future study. Copyright © 2008 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND: Persons belonging to the working class or living in an adverse social environment at particular periods of their life course may have an increased risk of chronic kidney disease (CKD). METHODS: This hypothesis was examined among participants of the Life Course Socioeconomic Status Study, an ancillary study of the Atherosclerosis Risk in Communities Study, conducted in 2001 (mean age, 67.4 years; N = 12,631). CKD was defined by hospital discharge diagnosis and/or estimated glomerular filtration rate less than 45 mL/min/1.73 m(2) (<0.75 mL/s/1.73 m(2)). Social class was categorized as working class or non-working class at ages 30, 40, or 50 years. Area-level socioeconomic status was based on a composite of census scores during the same period. Adjusted odds ratios were obtained within strata of white and African-American race. RESULTS: The adjusted odds ratio of CKD for persons belonging to the working class versus non-working class at age 30 was 1.4 (95% confidence interval, 1.0 to 2.0) in whites and 1.9 (95% confidence interval, 1.1 to 3.0) in African Americans. Working class membership was associated with CKD, even at earlier stages of adult life, and class was associated more strongly with CKD than was education. Working class membership also suggested a stronger association with CKD among African Americans than whites, independent of diabetes and hypertension status. At later periods in the life course, area socioeconomic status was associated with CKD. CONCLUSION: Socioeconomic factors, including area socioeconomic status and social class, are associated with CKD and may account for some of the racial disparity in kidney disease. Copyright © 2007 by the National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND: Obesity and metabolic syndrome may differ by race. For participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP), we examined whether African American and white participants with obesity and metabolic syndrome differ regarding albuminuria, estimated glomerular filtration rate (eGFR), anemia, and bone/mineral metabolism derangements in chronic kidney disease (CKD). METHODS: 3 study cohorts were assembled: (1) eligible African American and white KEEP participants with body mass index > or = 30 kg/m(2), (2) a subgroup meeting criteria for metabolic syndrome, and (3) a subgroup with eGFR < 60 mL/min/1.73 m(2) and laboratory measurements for hemoglobin, parathyroid hormone, calcium, and phosphorus. Patient characteristics and kidney function assessments were compared and tested using chi(2) (categorical variables) and t test (continuous variables). Univariate and multivariate logistic regression analyses were performed to evaluate associations of race with kidney disease measures. RESULTS: Of 37,107 obese participants, 48% were African American and 52% were white. Whites were more likely to have metabolic syndrome components (hypertension, 87.1% vs 84.8%; dyslipidemia, 81.6% vs 66.7%; diabetes, 42.7% vs 34.9%) and more profoundly decreased eGFR than African Americans (CKD stages 3-5 prevalence, 23.6% vs 13.0%; P < 0.001). African Americans were more likely to have abnormal urinary albumin excretion (microalbuminuria, 12.5% vs 10.2%; OR, 1.60 [95% CI, 1.45-1.76]; macroalbuminuria, 1.3% vs 1.2%; OR, 1.61 [95% CI, 1.23-2.12]) and CKD stages 1-2 (10.3% vs 7.1%; OR, 1.54 [95% CI, 1.38-1.72]). For participants with CKD stages 3-5, anemia prevalence was 32.4% in African Americans and 14.1% in whites; corresponding values for secondary hyperparathyroidism were 66.2% and 46.6%, respectively. CONCLUSIONS: Obesity and metabolic syndrome may be heterogeneous disease states in African Americans and whites, possibly explaining differences in long-term kidney and cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

The authors investigated the cumulative effects of life course social class and neighborhood socioeconomic conditions on the prevalence of chronic kidney disease (CKD) in adulthood. Subjects were members of the Atherosclerosis Risk in Communities (ARIC) Study, a longitudinal cohort study of four US communities. CKD was defined by glomerular filtration rate <45ml/min/1.73m(2) or hospital discharge diagnosis. Working class was defined by workplace roles for subjects and their fathers; area socioeconomic status (SES) was based on census information. Being working class for all life course periods or for some life course periods was associated with increased odds of CKD, compared to being non-working class for all periods (adjusted odds ratio, OR, for all periods (95% confidence interval) 1.4 (0.9, 2.0) in Whites and 1.9 (1.3, 2.9) in African-Americans; OR for some periods 1.3 (1.0, 1.9) in Whites and 1.4 (0.9, 2.2) in African-Americans). Low area SES over the life course was not significantly related to CKD compared to living in a higher SES areas at all life course periods. Adjustment for age, gender, community of residence, cumulative social class (for neighborhood measures), cumulative low-neighborhood SES (for cumulative individual social class), hypertension and diabetes does not account for these associations. Our conclusion is that chronic kidney disease is associated with life course socioeconomic conditions. As such, life course social class and neighborhood conditions deserve further attention in accounting for socioeconomic disparities in kidney disease. [ABSTRACT FROM AUTHOR]

Introduction: In many parts of the world, ambient temperatures have increased due to climate change. Due to loss of renal function, which impacts the regulation of thermoregulatory mechanisms, the ability to adapt and to be resilient to changing conditions is particularly concerning among individuals with kidney failure. The aim of this study was to assess the effect of heat on mortality and health care utilization among US patients on hemodialysis., Methods: We conducted a retrospective analysis from 2011 to 2016 in the contiguous United States during warmer months among eligible patients on dialysis who were identified in the United States Renal Data System (USRDS). Daily ambient temperature was estimated on a 1 km grid and assigned to ZIP-code. Case-crossover design with conditional Poisson models were used to assess the risk of developing adverse health outcomes associated with temperature exposure., Results: Overall, exposure to high temperature is associated with elevated risk for both mortality and health care utilization among hemodialysis patients. The risk ratios for all-cause mortality and daily temperature were 1.07 (95% confidence interval [CI]: 1.03-1.11), 1.17 (1.14-1.21) for fluid disorder-related hospital admissions, and 1.19 (1.16-1.22) for cardiovascular event-related emergency department (ED) visits, comparing 99th percentile versus 50th percentile daily temperatures. Larger effects were observed for cumulative lagged exposure 3 days prior to the outcome and for Southwest and Northwest climate regions., Conclusion: Heat exposure is associated with elevated risk for cardiovascular disease (CVD)-related mortality and health care utilization among this vulnerable population. Furthermore, the effect appears to be potentially cumulative in the short-term and varies geographically., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Environmental contributors to kidney disease progression remain elusive. We explored how residential air pollution affects disease progression in patients with primary glomerulopathies., Methods: Nephrotic Syndrome Study Network (NEPTUNE) and CureGlomerulonephropathy (CureGN) participants with residential census tract data and ≥2 years of follow-up were included. Using Cox proportional hazards models, the associations per doubling in annual average baseline concentrations of total particulate matter with diameter ≤2.5 μm (PM 2.5 ) and its components, black carbon (BC), and sulfate, with time to ≥40% decline in estimated glomerular filtration rate (eGFR) or kidney failure were estimated. Serum tumour necrosis factor levels and kidney tissue transcriptomic inflammatory pathway activation scores were used as molecular markers of disease progression., Results: PM 2.5 , BC, and sulfate exposures were comparable in NEPTUNE ( n  = 228) and CureGN ( n  = 697). In both cohorts, participants from areas with higher levels of pollutants had lower eGFR, were older and more likely self-reported racial and ethnic minorities. In a fully adjusted model combining both cohorts, kidney disease progression was associated with PM 2.5 (adjusted hazard ratio 1.55 [95% confidence interval: 1.00-2.38], P  = 0.0489) and BC (adjusted hazard ratio 1.43 [95% confidence interval: 0.98-2.07], P  = 0.0608) exposure. Sulfate and PM 2.5 exposure were positively correlated with serum tumour necrosis factor (TNF) ( P  = 0.003) and interleukin-1β levels ( P  = 0.03), respectively. Sulfate exposure was also directly associated with transcriptional activation of the TNF and JAK-STAT signaling pathways in kidneys (r = 0.55-0.67, P -value <0.01)., Conclusion: Elevated exposure to select air pollutants is associated with increased risk of disease progression and systemic inflammation in patients with primary., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Rationale & Objective: About 25%-40% of patients with inflammatory bowel disease (IBD) may have extraintestinal manifestations, mainly involving the liver, skin, and joints. Kidney involvement in patients with IBD has been reported, but there are no estimates of its prevalence in population-based studies in the United States. We compared the frequency of acute kidney injury (AKI) among hospitalizations with IBD with that among hospitalizations with collagen vascular diseases and hospitalizations with neither condition., Study Design: Retrospective, population-based cohort study., Setting & Participants: Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database., Outcomes: AKI and AKI requiring dialysis., Analytical Approach: Regression models were used to compare the occurrence of AKI among groups. Inverse probability of treatment weighting was applied to balance groups on covariates., Results: The final sample comprised 5,735,804 hospitalizations, including 57,121 with IBD, 159,930 with collagen vascular diseases, and 5,518,753 with neither IBD nor collagen vascular diseases. AKI was observed in 13%, 15%, and 12.2% of hospitalizations with IBD, collagen vascular diseases, and the general population, respectively. When adjusting for demographic, hospital, and clinical characteristics using inverse probability of treatment weighting, hospitalizations with IBD had higher odds of being diagnosed with AKI than both those with collagen vascular diseases (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.27-1.38) and the general population (OR, 1.27; 95% CI, 1.23-1.31) and also had higher odds of being diagnosed with AKI requiring dialysis than those with collagen vascular diseases (OR, 1.59; 95% CI, 1.31-1.94) or than the general population (OR, 1.45; 95% CI, 1.25-1.68)., Limitations: Cross-sectional analysis, underreporting of International Classification of Diseases codes, and analyses relevant to in-hospital stays only., Conclusions: The prevalence and risk of AKI among hospitalizations with IBD is greater than that of hospitalizations with collagen vascular diseases and the general population. Coexisting kidney disease should be considered among patients with a known diagnosis of IBD., (© 2024 The Authors.)

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 (eGFR cr ) and diagnosis of CKD and potential associations with fine particulate matter (PM 2.5 ), ozone (O 3 ), and nitrogen dioxide (NO 2 ) using a random sample of North Carolina electronic healthcare records (EHRs) from 2004 to 2016. We estimated eGFR cr using the serum creatinine-based 2021 CKD-EPI equation. PM 2.5 and NO 2 data come from a hybrid model using 1 km 2 grids and O 3 data from 12 km 2 CMAQ grids. Exposure concentrations were 1-year averages. We used linear mixed models to estimate eGFR cr 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/1.73m 2 (95% CI: -1.96, -1.31) reduction in eGFRcr, with O 3 and NO 2 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 eGFR cr  < 60 mL/min/1.73m 2 . NO 2 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 PM 2.5 was associated with reduced eGFR cr , while O 3 and NO 2 were inversely associated. Neither PM 2.5 or O 3 were associated with a first-time identification of CKD, NO 2 was inversely associated. We recommend future research examining the relationship between air pollution and impaired renal function., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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 (β, -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 (β, 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 (β, -1.55; 95% CI, -3.08 to -0.01; P = .05); however, depression (β, -0.18; 95% CI, -2.09 to 1.73; P = .84) and posttraumatic distress (β, -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.

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., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 by the American Society of Nephrology.)

Rationale & Objective: Ambient PM 2.5 (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 PM 2.5 exposure and CV outcomes in the setting of kidney disease are limited. This study assessed the association of long-term PM 2.5 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 PM 2.5 concentrations were used to calculate each participant's annual average PM 2.5 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/m 3 greater annual average PM 2.5 , 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/m 3 greater annual average PM 2.5 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 PM 2.5 exposure was associated with CVD outcomes among patients receiving maintenance in-center HD. Stronger associations between long-term PM 2.5 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 PM 2.5 , has been linked to adverse cardiovascular outcomes. However, little is known about the association of PM 2.5 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 PM 2.5 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., (Published by Elsevier Inc.)

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., Competing Interests: N. Franceschini reports serving on the editorial boards of American Journal of Physiology–Renal Physiology and Contemporary Clinical Trials; and serving in an advisory or leadership role as a convener for the National Heart, Lung, and Blood Institute TOPMed kidney working group, as vice-chair of the Women’s Health Initiative Ancillary Committee, and on the Women’s Health Initiative Publication and Presentation Committee. A.V. Kshirsagar reports having consultancy agreements with Alkahest, Rockwell, and Target RWE; serving on the editorial boards of American Journal of Kidney Disease and Kidney Medicine; and having royalties with UpToDate (as contributor). E.M. Zeitler reports receiving research funding, via spouse, from Dexcom, Novo Nordisk, Rhythm Pharmaceuticals, and VTV Therapeutics. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

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., (Copyright © 2022 by the American Society of Nephrology.)

Background: Ambient PM 2.5 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 PM 2.5 exposure. This study examines associations between short-term PM 2.5 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 PM 2.5 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 PM 2.5 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/m 3 increase in the average lag 0-1 daily PM 2.5 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 PM 2.5 exposure was positively associated with incident CVD events and mortality among patients receiving in-center hemodialysis. Older patients appeared to be more susceptible to PM 2.5 -associated CVD events than younger hemodialysis patients., (© 2022. The Author(s).)

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.

Competing Interests: A.V. Kshirsagar reports consultancy agreements with Rockwell Medical; honoraria as a contributor to UpToDate since 2006; and scientific advisor or membership with American Journal of Kidney Disease and Kidney Medicine. The remaining author has nothing to disclose.

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., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

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., (© 2021 The Authors.)

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.

The glycopeptide antibiotic vancomycin is a mainstay in the treatment of Gram-positive infection. While its association with acute kidney injury (AKI) has waxed and waned, recent data suggest nephrotoxicity, even as mono-therapy. Our study aimed to evaluate the 2-week risk of AKI after at least 3 days of intravenous vancomycin mono-therapy initiated within 5 days of hospitalization compared to other intravenous antibiotics used for similar indications. We used a new user-active comparator study design and identified patients with a first hospitalization during which they received vancomycin or comparator, from commercial claims based in the United States. We estimated incidence rates, hazard ratios using adjusted cox-regression models, and standardized mortality/morbidity ratio weighted cox-regression models. In the 32,997 patients vancomycin was used in 17% of patients and 129 cases of AKI were observed. Overall incidence of AKI was 9.3 (95% CI 0.78-1.22) per 100 person-years. The adjusted hazard ratio for vancomycin versus all other comparators was 0.74 (95% CI 0.45-1.21). Separate models for respective comparators resulted in hazard ratios below the null, except for vancomycin vs. cefazolin. Intravenous vancomycin mono-therapy does not increase the risk of AKI compared to other intravenous antibiotics used for similar indication in this cohort of hospitalized patients.

Background: Pulmonary hypertension (PH) is frequently reported in patients with advanced chronic kidney disease and is associated with early allograft failure and death. However, the causes of PH are heterogeneous, and patient prognosis may vary by etiologic subtype., Methods: Data from the University of North Carolina Cardiorenal Registry were examined to determine associations between PH, with or without elevated left atrial pressure (eLAP), and mortality in candidates for kidney transplantation. PH and eLAP were determined by Doppler echocardiography and by tissue Doppler imaging, respectively., Results: From 2006 to 2013, 778 registry patients were screened preoperatively by echocardiography. Most patients were black (64%) and men (56%); the mean age was 56 years. PH was identified in 97 (12%) patients; of these, eLAP was prevalent in half. During a median follow-up of 4.4 years, 179 (23%) received a kidney transplant, and 195 (25%) died. After adjustments for demographics, comorbidities, dialysis vintage, and kidney transplantation, PH was associated with twice the 5-year mortality (hazard ratio [HR] = 2.11; 95% confidence interval [CI]: 1.48-3.03), with stronger associations in the absence of eLAP (HR = 2.87; 95% CI: 1.83-4.49) than with eLAP (HR = 1.11; 95% CI: 0.57-2.17), P for interaction = 0.01., Conclusions: The mortality risk associated with PH among patients with advanced chronic kidney disease appears to differ by etiology. Patients with PH in the absence of eLAP are at high risk of death and in need of focused attention. Future research efforts should investigate potential strategies to improve outcomes for these patients.

Background: Wildfires are increasingly a significant source of fine particulate matter (PM 2.5 ), which has been linked to adverse health effects and increased mortality. ESKD patients are potentially susceptible to this environmental stressor., Methods: We conducted a retrospective time-series analysis of the association between daily exposure to wildfire PM 2.5 and mortality in 253 counties near a major wildfire between 2008 and 2012. Using quasi-Poisson regression models, we estimated rate ratios (RRs) for all-cause mortality on the day of exposure and up to 30 days following exposure, adjusted for background PM 2.5 , day of week, seasonality, and heat. We stratified the analysis by causes of death (cardiac, vascular, infectious, or other) and place of death (clinical or nonclinical setting) for differential PM 2.5 exposure and outcome classification., Results: We found 48,454 deaths matched to the 253 counties. A 10- μ g/m 3 increase in wildfire PM 2.5 associated with a 4% increase in all-cause mortality on the same day (RR, 1.04; 95% confidence interval [95% CI], 1.01 to 1.07) and 7% increase cumulatively over 30 days following exposure (RR, 1.07; 95% CI, 1.01 to 1.12). Risk was elevated following exposure for deaths occurring in nonclinical settings (RR, 1.07; 95% CI, 1.02 to 1.12), suggesting modification of exposure by place of death. "Other" deaths (those not attributed to cardiac, vascular, or infectious causes) accounted for the largest portion of deaths and had a strong same-day effect (RR, 1.08; 95% CI, 1.03 to 1.12) and cumulative effect over the 30-day period. On days with a wildfire PM 2.5 contribution >10 μ g/m 3 , exposure accounted for 8.4% of mortality., Conclusions: Wildfire smoke exposure was positively associated with all-cause mortality among patients receiving in-center hemodialysis., (Copyright © 2020 by the American Society of Nephrology.)

Background: Because functioning permanent vascular access (arteriovenous fistula [AVF] or arteriovenous graft [AVG]) is crucial for optimizing patient outcomes for those on hemodialysis, the supply of physicians placing vascular access is key. We investigated whether area-level demographic and healthcare market attributes were associated with the distribution and supply of AVF/AVG access physicians in the United States., Methods: A nationwide registry of physicians placing AVFs/AVGs in 2015 was created using data from the United States Renal Data System and the American Physician Association's Physician Masterfile. We linked the registry information to the Area Health Resource File to assess the supply of AVF/AVG access physicians and their professional attributes by hospital referral region (HRR). Bivariate analysis and Poisson regression were performed to examine the relationship between AVF/AVG access physician supply and demographic, socioeconomic, and health resource conditions of HRRs. The setting included all 50 states. The main outcome was supply of AVF/AVG access physicians, defined as the number of physicians performing AVF and/or AVG placement per 1000 prevalent patients with ESKD., Results: The majority of vascular access physicians were aged 45-64 (average age, 51.6), male (91%), trained in the United States (76%), and registered in a surgical specialty (74%). The supply of physicians varied substantially across HRRs. The supply was higher in HRRs with a higher percentage white population ( β =0.44; SEM=0.14; P =0.002), lower unemployment rates ( β =-10.74; SEM=3.41; P =0.002), and greater supply of primary care physicians ( β =0.18; SEM=0.05; P =0.001) and nephrologists ( β =15.89; SEM=1.22; P <0.001)., Conclusions: Geographic variation was observed in the supply of vascular access physicians. Higher supply of such specialist physicians in socially and economically advantaged areas may explain disparities in vascular access and outcomes in the United States and should be the subject of further study and improvement.

Background: Dialysis care often focuses on outcomes that are of lesser importance to patients than to clinicians. There is growing international interest in individualizing care based on patient priorities, but evidence-based approaches are lacking. The objective of this study was to develop a person-centered dialysis care planning program. To achieve this objective we performed qualitative interviews, responsively developed a novel care planning program and then assessed program content and burden., Methods: We conducted 25 concept elicitation interviews with US hemodialysis patients, care partners and care providers, using thematic analysis to analyze transcripts. Interview findings and interdisciplinary stakeholder panel input informed the development of a new care planning program, My Dialysis Plan. We then conducted 19 cognitive debriefing interviews with patients, care partners and care providers to assess the program's content and face validities, comprehensibility and burden., Results: We identified five themes in concept elicitation interviews: feeling boxed in by the system, navigating dual lives, acknowledging an evolving identity, respecting the individual as a whole person and increasing individualization to enhance care. We then developed a person-centered care planning program and supporting materials that underwent 32 stakeholder-informed iterations. Data from subsequent cognitive interviews led to program revisions intended to improve contextualization and understanding, decrease burden and facilitate implementation., Conclusions: My Dialysis Plan is a content-valid, person-centered dialysis care planning program that aims to promote care individualization. Investigation of the program's capacity to improve patient experiences and outcomes is needed., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

The Advancing American Kidney Health executive order aims to reduce the incidence of end-stage kidney disease, promote home dialysis therapies, increase the number of kidney transplants, and encourage innovation in new technologies, evidence-based practice, and early detection of kidney disease. Improvements in dialysis access care are essential to the success and expansion of this program, and to being able to provide high-quality, cost-efficient care to this patient population. Specifically, the need for expanded access to home dialysis will require surgeons and interventionalists to become proficient and trained in peritoneal dialysis catheter placement and for the referral process to be streamlined to accommodate the increased interest in this modality. In addition, new technologies, namely percutaneous fistula creation, bioengineered vessels, and a variety of interventions to reduce arteriovenous stenosis, will hopefully allow for timely and durable vascular access options that will support implementation of the executive order., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Quantitative metrics are used to develop profiles of health care institutions, including hospitals, nursing homes, and dialysis clinics. These profiles serve as measures of quality of care, which are used to compare institutions and determine reimbursement, as a part of a national effort led by the Center for Medicare and Medicaid Services in the United States. However, there is some concern about how misclassification in case-mix factors, which are typically accounted for in profiling, impacts results. We evaluated the potential effect of misclassification on profiling results, using 20 744 patients from 2740 dialysis facilities in the US Renal Data System. In this case study, we compared 30-day readmission as the profiling outcome measure, using comorbidity data from either the Center for Medicare and Medicaid Services Medical Evidence Report (error-prone) or Medicare claims (more accurate). Although the regression coefficient of the error-prone covariate demonstrated notable bias in simulation, the outcome measure-standardized readmission ratio-and profiling results were quite robust; for example, correlation coefficient of 0.99 in standardized readmission ratio estimates. Thus, we conclude that misclassification on case-mix did not meaningfully impact overall profiling results. We also identified both extreme degree of case-mix factor misclassification and magnitude of between-provider variability as 2 factors that can potentially exert enough influence on profile status to move a clinic from one performance category to another (eg, normal to worse performer).

Sickle cell trait (SCT) has been associated with hypercoagulability, chronic kidney disease (CKD), and ischemic stroke. Whether concomitant CKD modifies long-term ischemic stroke risk in individuals with SCT is uncertain. We analyzed data from 3602 genotyped black adults (female = 62%, mean baseline age = 54 years) who were followed for a median 26 years by the Atherosclerosis Risk in Communities Study. Ischemic stroke was verified by physician review. Associations between SCT and ischemic stroke were analyzed using repeat-events Cox regression, adjusted for potential confounders. SCT was identified in 236 (7%) participants, who more often had CKD at baseline than noncarriers (18% vs 13%, P = .02). Among those with CKD, elevated factor VII activity was more prevalent with SCT genotype (36% vs 22%; P = .05). From 1987-2017, 555 ischemic strokes occurred in 436 individuals. The overall hazard ratio of ischemic stroke associated with SCT was 1.31 (95% CI: 0.95-1.80) and was stronger in participants with concomitant CKD (HR = 2.18; 95% CI: 1.16-4.12) than those without CKD (HR = 1.09; 95% CI: 0.74-1.61); P for interaction = .04. The hazard ratio of composite ischemic stroke and/or death associated with SCT was 1.20 (95% CI: 1.01-1.42) overall, 1.44 (95% CI: 1.002-2.07) among those with CKD, and 1.15 (95% CI: 0.94-1.39) among those without CKD; P for interaction = .18. The long-term risk of ischemic stroke associated with SCT relative to noncarrier genotype appears to be modified by concomitant CKD., (© 2019 Wiley Periodicals, Inc.)

Objective: The incidence and prevalence of cognitive decline and dementia are significantly higher among African Americans compared with non-Hispanic Whites. The aim of this study was to determine whether inheritance of the sickle cell trait (SCT) i.e. heterozygosity for the sickle cell mutation increases the risk of cognitive decline or dementia Among African Americans., Methods: We studied African American participants enrolled in the Atherosclerosis Risk in Communities study. SCT genotype at baseline and outcome data from cognitive assessments at visits 2, 4 and 5, and an MRI performed at visit 5 were analyzed for the association between SCT and risk of cognitive impairment and/or dementia., Results: There was no significant difference in risk factors profile between participants with SCT ( N  = 176) and those without SCT ( N  = 2532). SCT was not independently associated with a higher prevalence of global or domain-specific cognitive impairment at baseline or with more rapid cognitive decline. Participants with SCT had slightly lower incidence of dementia (HR = 0.63 [0.38, 1.05]). On the other hand, SCT seems to interact with the apolipoprotein E ε4 risk allele resulting in poor performance on digit symbol substitution test at baseline (z-score = -0.08, P interaction  = 0.05) and over time (z-score = -0.12, P interaction  = 0.04); and with diabetes mellitus leading to a moderately increased risk of dementia (HR = 2.06 [0.89, 4.78], P interaction  = 0.01)., Conclusions: SCT was not an independent risk factor for prevalence or incidence of cognitive decline or dementia, although it may interact with and modify other putative risk factors for cognitive decline and dementia.

Patients with end-stage renal disease on dialysis commonly receive intravenous iron to treat anemia along with erythropoiesis-stimulating agents. While studies of intravenous iron have demonstrated efficacy in raising hemoglobin, the quantity of administered intravenous iron has raised concerns about iron overload leading to long-term toxicities. The goal of this review is to understand recent trends in intravenous iron use, potential mechanisms of iron toxicity, and to evaluate the available evidence in the literature for potential long-term cardiovascular and infectious complications. We include findings from the recently published landmark clinical trial of intravenous iron for patients receiving hemodialysis to contextualize treatment recommendations., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Intravenous iron therapy for chronic anemia management is largely driven by dosing protocols that differ in intensity with respect to dosing approach ( i.e. , dose, frequency, and duration). Little is known about the safety of these protocols., Design, Setting, Participants, & Measurements: Using clinical data from a large United States dialysis provider linked to health care utilization data from Medicare, we constructed a cohort of patients with ESKD aged ≥65 years who initiated and continued center-based hemodialysis for ≥90 days between 2009 and 2012, and initiated at least one of the five common intravenous iron administration strategies; ranked by intensity (the amount of iron given at moderate-to-high iron indices), the order of strategies was 3 (least intensive), 2 (less intensive), 1 (reference), 4 (more intensive), and 5 (most intensive). We estimated the effect of continuous exposure to these strategies on cumulative risks of mortality and infection-related events with dynamic Cox marginal structural models., Results: Of 13,249 eligible patients, 1320 (10%) died and 1627 (12%) had one or more infection-related events during the 4-month follow-up. The most and least commonly initiated strategy was strategy 2 and 5, respectively. Compared with the reference strategy 1, more intensive strategies (4 and 5) demonstrated a higher risk of all-cause mortality ( e.g. , most intensive strategy 5: 60-day risk difference: 1.3%; 95% confidence interval [95% CI], 0.8% to 2.1%; 120-day risk difference: 3.1%; 95% CI, 1.0% to 5.6%). Similarly, higher risks were observed for infection-related morbidity and mortality among more intensive strategies ( e.g. , strategy 5: 60-day risk difference: 1.8%; 95% CI, 1.2% to 2.6%; 120-day risk difference: 4.3%; 95% CI, 2.2% to 6.8%). Less intensive strategies (2 and 3) demonstrated lower risks of all-cause mortality and infection-related events., Conclusions: Among dialysis patients surviving 90 days, subsequent intravenous iron administration strategies promoting more intensive iron treatment at moderate-to-high iron indices levels are associated with higher risks of mortality and infection-related events., (Copyright © 2019 by the American Society of Nephrology.)

The Dialysis Facility Compare Star Rating and the Quality Incentive Program (QIP) generate separate performance scores from clinical measures, and the In-Center Hemodialysis Consumer Assessment of Healthcare Providers and Systems (ICH-CAHPS) survey evaluates patient satisfaction across 6 separate domains related to nephrologists, dialysis facility, and information transmission. This study examined the relationship of the 3 measures for US clinics, modeling the 6 ICH-CAHPS domains as independent variables and QIP and star ratings as dependent variables. Among 3176 dialysis clinics, domains assessing dialysis facility and information transmission had a consistently stronger relationship with QIP and star ratings than the domains assessing nephrologists: QIP, β (95% CI) = 1.62 (1.26-1.97) for dialysis facility staff rating, 0.70 (0.35-1.05) for nephrologists; star rating, odds ratio (95% CI) = 1.38 (1.29-1.49) for dialysis facility staff rating, 1.17 (1.09-1.25) for nephrologists. Patient satisfaction is associated with dialysis care quality, with surprising differences between nephrologists and dialysis facilities.

Background: Estimating influenza vaccine effectiveness using an unvaccinated comparison group may result in biased effect estimates., Objectives: To explore the reduction of confounding bias in an active comparison of high-dose versus standard-dose influenza vaccines, as compared with vaccinated versus unvaccinated comparisons., Methods: Using Medicare data from the United States end-stage renal disease program (2009-2013), we compared the risk of all-cause mortality among recipients of high-dose vaccine (HDV) versus standard-dose vaccine (SDV), HDV versus no vaccine, and SDV versus no vaccine. To quantify confounding bias, analyses were restricted to the preinfluenza season, when the protective effect of vaccination should not yet be observed. We estimated the standardized mortality ratio-weighted cumulative incidence functions using Kaplan-Meier methods and calculated risk ratios (RRs) and risk differences between groups., Results: Among 350,921 eligible patients contributing 825,642 unique patient preinfluenza seasons, 0.8% received HDV, 70.5% received SDV, and 28.7% remained unvaccinated. Comparisons with unvaccinated patients yielded spurious decreases in mortality risk during the preinfluenza period, for HDV versus none [RR, 0.60; 95% confidence interval (CI), 0.51-0.70)] and SDV versus none (RR, 0.72; 95% CI, 0.70-0.75). The effect estimate was attenuated in the HDV versus SDV comparison (RR, 0.89; 95% CI, 0.77-1.03). Estimates on the absolute scale followed a similar pattern., Conclusions: The HDV versus SDV comparison yielded less-biased estimates of the all-cause mortality before influenza season compared to those with nonuser comparison groups. Vaccine effectiveness and safety researchers should consider the active comparator design to reduce bias due to differences in underlying health status between vaccinated and unvaccinated individuals.