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.

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.

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.

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.

Mortality in US Hemodialysis Patients Following Exposure to Wildfire Smoke.

BACKGROUND: Wildfires are increasingly a significant source of fine particulate matter (PM2.5), 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 PM2.5 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 PM2.5, 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 PM2.5 exposure and outcome classification. RESULTS: We found 48,454 deaths matched to the 253 counties. A 10-µg/m3 increase in wildfire PM2.5 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 PM2.5 contribution >10 µg/m3, exposure accounted for 8.4% of mortality. CONCLUSIONS: Wildfire smoke exposure was positively associated with all-cause mortality among patients receiving in-center hemodialysis.

Development of a person-centered interdisciplinary plan-of-care program for dialysis.

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.

Assessing Residual Bias in Estimating Influenza Vaccine Effectiveness: Comparison of High-dose Versus Standard-dose Vaccines.

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.

Thirty-year risk of ischemic stroke in individuals with sickle cell trait and modification by chronic kidney disease: The atherosclerosis risk in communities (ARIC) study.

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.

Association Between Gestational Diabetes and Incident Maternal CKD: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with increased risk for diabetes mellitus, metabolic syndrome, and cardiovascular disease. We evaluated whether GDM is associated with incident chronic kidney disease (CKD), controlling for prepregnancy risk factors for both conditions. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: Of 2,747 women (aged 18-30 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study in 1985 to 86, we studied 820 who were nulliparous at enrollment, delivered at least 1 pregnancy longer than 20 weeks' gestation, and had kidney function measurements during 25 years of follow-up. PREDICTOR: GDM was self-reported by women for each pregnancy. OUTCOMES: CKD was defined as the development of estimated glomerular filtration rate (eGFR)<60mL/min/1.73m2 or urine albumin-creatinine ratio ≥ 25mg/g at any one CARDIA examination in years 10, 15, 20, or 25. MEASUREMENTS: HRs for developing CKD were estimated for women who developed GDM versus women without GDM using complementary log-log models, adjusting for prepregnancy age, systolic blood pressure, dyslipidemia, body mass index, smoking, education, eGFR, fasting glucose concentration, physical activity level (all measured at the CARDIA examination before the first pregnancy), race, and family history of diabetes. We explored for an interaction between race and GDM. RESULTS: During a mean follow-up of 20.8 years, 105 of 820 (12.8%) women developed CKD, predominantly increased urine albumin excretion (98 albuminuria only, 4 decreased eGFR only, and 3 both). There was evidence of a GDM-race interaction on CKD risk (P=0.06). Among black women, the adjusted HR for CKD was 1.96 (95% CI, 1.04-3.67) in GDM compared with those without GDM. Among white women, the HR was 0.65 (95% CI, 0.23-1.83). LIMITATIONS: Albuminuria was assessed by single untimed measurements of urine albumin and creatinine. CONCLUSIONS: GDM is associated with the subsequent development of albuminuria among black women in CARDIA.

Regional and Temporal Variations in Comorbidity Among US Dialysis Patients: A Longitudinal Study of Medicare Claims Data.

Medicare claims data are commonly used to query comorbidities for case-mix adjustment in research of patients with end-stage renal disease (ESRD) in the United States. These adjustments may affect reimbursement and quality rating through comparative profiling and ranking of dialysis facilities. We studied regional and temporal variations in comorbidity from claims data in the United States Renal Data System. Patients with a previous 1-year Medicare history who initiated dialysis therapy between 2006 and 2009 were examined with a follow-up period until 2012. By linking pre- and post-ESRD Medicare claims with the Dartmouth Atlas, we carried out a longitudinal data analysis with multivariable adjustment to investigate regional and temporal variations in the Liu comorbidity index. We identified 23 336 incident hemodialysis patients who were covered by Medicare the year prior to dialysis initiation and had survived with complete 3 years of follow-up data. With the United States divided into 4 geographic regions, the Western region was found to have the lowest Liu index over all 3 follow-up years, compared with the respective years in the other regions (Midwest, Northeast, and South). In comparison with the first year, the Liu index dropped significantly during the second and third years of follow-up across all 4 regions. Significant regional and temporal variations observed in the comorbidity index cannot be explained by differences in reimbursement (average per state) or predialysis comorbidity. Based on our exploratory study, future studies should focus on identifying the factors and reasons for these variations which have the potential to affect health care policy and research.

Excess Readmission-Based Penalty: Is Arthroplasty Different From the Other Outcomes?

Whether factors not under a hospital's control affect readmissions remains intensely debated in the context of the Centers for Medicare & Medicaid Services' Hospital Readmission Reduction Program. This study aimed to evaluate the potential effects of poverty, race, and hospital volume on excess readmissions, with >3000 hospitals participating in "Hospital Compare." Correlations between excess readmission ratios for five eligible outcomes (including hip and knee arthroplasty) were assessed with the three area and hospital-level factors: poverty, race (percent of black population), and hospital volume (number of discharges). Correlation coefficients of the ratios with race were approximately r = 0.2, consistently larger than those with poverty (r = 0-0.1), and those with volume were r = 0 to -0.5. Hip and knee arthroplasty had unique findings: null correlation with poverty (r ≈ 0), largest variability, and strong monotonicity with volume (r ≈ -0.5). The percent of Hispanic population showed negligible correlations in secondary analysis. Penalty assessment and hospital profiling should consider areas with high percentages of black population and a small volume of hospitals and providers of hip and knee surgery. (Journal of Surgical Orthopaedic Advances 27(4):286-294, 2018).

Psychosocial Factors and 30-Day Hospital Readmission among Individuals Receiving Maintenance Dialysis: A Prospective Study.

BACKGROUND: Thirty-day hospital readmissions are common among maintenance dialysis patients. Prior studies have evaluated easily measurable readmission risk factors such as comorbid conditions, laboratory results, and hospital discharge day. We undertook this prospective study to investigate the associations between hospital-assessed depression, health literacy, social support, and self-rated health (separately) and 30-day hospital readmission among dialysis patients. METHODS: Participants were recruited from the University of North Carolina Hospitals, 2014-2016. Validated depression, health literacy, social support, and self-rated health screening instruments were administered during index hospitalizations. Multivariable logistic regression models with 30-day readmission as the dependent outcome were used to examine readmission risk factors. RESULTS: Of the 154 participants, 58 (37.7%) had a 30-day hospital readmission. In unadjusted analyses, individuals with positive screening for depression, lower health literacy, and poorer social support were more likely to have a 30-day readmission (vs. negative screening). Positive depression screening and poorer social support remained significantly associated with 30-day readmission in models adjusted for race, heart failure, admitting service, weekend discharge day, and serum albumin: adjusted OR (95% CI) 2.33 (1.02-5.15) for positive depressive symptoms and 2.57 (1.10-5.91) for poorer social support. The area under the receiver operating characteristic curve (AUC) of the multivariable model adjusted for social support status was significantly greater than the AUC of the multivariable model without social support status (test for equality; p value = 0.04). CONCLUSION: Poor social support and depressive symptoms identified during hospitalizations may represent targetable readmission risk factors among dialysis patients. Our findings suggest that hospital-based assessments of select psychosocial factors may improve readmission risk prediction.

Patients with primary membranous nephropathy are at high risk of cardiovascular events.

Here we conducted a retrospective study to examine the risk of cardiovascular events (CVEs) relative to that of end-stage renal disease (ESRD) in patients with primary membranous nephropathy, in a discovery cohort of 404 patients. The cumulative incidence of CVEs was estimated in the setting of the competing risk of ESRD with risk factors for CVEs assessed by multivariable survival analysis. The observed cumulative incidences of CVEs were 4.4%, 5.4%, 8.2%, and 8.8% at 1, 2, 3, and 5 years respectively in the primary membranous nephropathy cohort. In the first 2 years after diagnosis, the risk for CVEs was similar to that of ESRD in the entire cohort, but exceeded it among patients with preserved renal function. Accounting for traditional risk factors and renal function, the severity of nephrosis at the time of the event (hazard ratio 2.1, 95% confidence interval 1.1 to 4.3) was a significant independent risk factor of CVEs. The incidence and risk factors of CVEs were affirmed in an external validation cohort of 557 patients with primary membranous nephropathy. Thus early in the course of disease, patients with primary membranous nephropathy have an increased risk of CVEs commensurate to, or exceeding that of ESRD. Hence, reduction of CVEs should be considered as a therapeutic outcome measure and focus of intervention in primary membranous nephropathy.

Comparative Short-term Safety of Sodium Ferric Gluconate Versus Iron Sucrose in Hemodialysis Patients.

BACKGROUND: Despite different pharmacologic properties, little is known about the comparative safety of sodium ferric gluconate versus iron sucrose in hemodialysis patients. STUDY DESIGN: Retrospective cohort study using the clinical database of a large dialysis provider (2004-2005) merged with administrative data from the US Renal Data System. SETTING & PARTICIPANTS: 66,207 patients with Medicare coverage who received center-based hemodialysis. PREDICTORS: Iron formulation use assessed during repeated 1-month exposure periods (n=278,357). OUTCOMES: All-cause mortality, infection-related hospitalizations and mortality, and cardiovascular-related hospitalizations and mortality occurring during a 3-month follow-up period. MEASUREMENTS: For all outcomes, we estimated 90-day risk differences between the formulations using propensity score weighting of Kaplan-Meier functions, which controlled for a wide range of demographic, clinical, and laboratory variables. Risk differences were also estimated within various clinically important subgroups. RESULTS: Ferric gluconate was administered in 11.4%; iron sucrose, in 48.9%; and no iron in 39.7% of the periods. Risks for most study outcomes did not differ between ferric gluconate and iron sucrose; however, among patients with a hemodialysis catheter, use of ferric gluconate was associated with a slightly decreased risk for both infection-related death (risk difference, -0.3%; 95% CI, -0.5% to 0.0%) and infection-related hospitalization (risk difference, -1.5%; 95% CI, -2.3% to -0.6%). Bolus dosing was associated with an increase in infection-related events among both ferric gluconate and iron sucrose users. LIMITATIONS: Residual confounding and outcome measurement error. CONCLUSIONS: Overall, the 2 iron formulations studied exhibited similar safety profiles; however, ferric gluconate was associated with a slightly decreased risk for infection-related outcomes compared to iron sucrose among patients with a hemodialysis catheter. These associations should be explored further using other data or study designs.

Comparative Effectiveness of Iron and Erythropoiesis-Stimulating Agent Dosing on Health-Related Quality of Life in Patients Receiving Hemodialysis.

BACKGROUND: The potential effects of iron-dosing strategies and erythropoiesis-stimulating agents (ESAs) on health-related quality of life (HRQoL) in the dialysis population are unclear. We examined the independent associations of bolus versus maintenance iron dosing and high versus low ESA dosing on HRQoL. STUDY DESIGN: Retrospective cohort design. SETTING & PARTICIPANTS: Clinical data (2008-2010) from a large dialysis organization merged with data from the US Renal Data System. 13,039 patients receiving center-based hemodialysis were included. PREDICTOR: Iron and ESA dosing were assessed during 1-month (n=14,901) and 2-week (n=15,296) exposure periods. OUTCOMES: HRQoL was measured by the Kidney Disease Quality of Life (KDQOL) instrument (0-100 scale) during a 3-month follow-up period. MEASUREMENTS: Generalized linear mixed models, adjusting for several covariates, were used to estimate associations between iron and ESA dosing and HRQoL overall and for clinically relevant subgroups. RESULTS: For the 1-month exposure period, patients with lower baseline hemoglobin levels who received higher ESA dosing had higher physical health and kidney disease symptom scores (by 2.4 [95% CI, 0.6-4.2] and 5.6 [95% CI, 2.8-8.4] points, respectively) in follow-up than patients who received lower ESA dosing. For the 2-week exposure period, patients with low baseline hemoglobin levels who received bolus dosing had higher mental health scores (by 1.9 [95% CI, 0.0-3.8] points) in follow-up. Within the low-baseline-hemoglobin subgroup, individuals with a catheter or dialysis vintage less than 1 year who received higher ESA dosing had higher HRQoL scores in follow-up (by 5.0-9.9 points) and individuals with low baseline transferrin saturations who received bolus dosing had higher HRQoL scores in follow-up (by 2.6-5.8 points). LIMITATIONS: Observational design; short duration of observation. CONCLUSIONS: For individuals with low baseline hemoglobin levels, higher ESA dosing and bolus iron dosing were associated with slightly higher HRQoL scores in follow-up. These differences became more pronounced and clinically relevant for specific subgroups.

Cancer incidence among US Medicare ESRD patients receiving hemodialysis, 1996-2009.

BACKGROUND: Patients with end-stage renal disease (ESRD) receiving dialysis have been reported to have increased risk of cancer. However, contemporary cancer burden estimates in this population are sparse and do not account for the high competing risk of death characteristic of dialysis patients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: US adult patients enrolled in Medicare's ESRD program who received in-center hemodialysis. FACTORS: Demographic/clinical characteristics. OUTCOMES: For overall and site-specific cancers identified using claims-based definitions, we calculated annual incidence rates (1996-2009). We estimated 5-year cumulative incidence since dialysis therapy initiation using competing-risk methods. RESULTS: We observed a constant rate of incident cancers for all sites combined, from 3,923 to 3,860 cases per 100,000 person-years (annual percentage change, 0.1; 95% CI, -0.4 to 0.6). Rates for some common site-specific cancers increased (ie, kidney/renal pelvis) and decreased (ie, colon/rectum, lung/bronchus, pancreas, and other sites). Of 482,510 incident hemodialysis patients, cancer was diagnosed in 37,128 within 5 years after dialysis therapy initiation. The 5-year cumulative incidence of any cancer was 9.48% (95% CI, 9.39%-9.57%) and was higher for certain subgroups: older age, males, nonwhites, non-Hispanics, nondiabetes primary ESRD cause, recent dialysis therapy initiation, and history of transplantation evaluation. Among blacks and whites, we observed 35,767 cases compared with 25,194 expected cases if the study population had experienced rates observed in the US general population (standardized incidence ratio [SIR], 1.42; 95% CI, 1.41-1.43). Risk was most elevated for cancers of the kidney/renal pelvis (SIR, 4.03; 95% CI, 3.88-4.19) and bladder (SIR, 1.57; 95% CI, 1.51-1.64). LIMITATIONS: Claims-based cancer definitions have not been validated in the ESRD population. Information for cancer risk factors was not available in our data source. CONCLUSIONS: These results suggest a high burden of cancer in the dialysis population compared to the US general population, with varying patterns of cancer incidence in subgroups.

Trends in Anemia Management in Hemodialysis Patients with Cancer.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs), intravenous iron, and blood transfusion are used to treat anemia in both end-stage renal disease (ESRD) and cancer. However, anemia treatment patterns have not been described among ESRD patients undergoing hemodialysis with concurrent cancer, especially in the recent era of ESA-related safety concerns. METHODS: We analyzed Medicare data from a cohort of hemodialysis patients diagnosed with incident cancer. We used multivariable generalized linear models to estimate trends and patterns in ESA use, iron use, transfusion use, epoetin alfa (EPO) dose, iron dose, and resulting hemoglobin levels (2000-2011). RESULTS: Of 43,760 eligible patients, quarterly ESA use declined slightly from a peak of 94.1 to 90.0%. Quarterly EPO dose increased from 2000 to 2004, then declined; quarterly hemoglobin levels followed a similar pattern. Iron use increased rapidly from 46.9 to 79.3%. Iron dose increased until 2010 and then declined. There was an increase in the quarterly transfusion use (6.3-11.7%) and in the mean number of transfusion days per year (1.4-1.8). Anemia treatment patterns varied by demographic/clinical subgroups, especially among patients receiving chemotherapy, who required higher ESA use, EPO dose, and frequency of transfusions. CONCLUSIONS: Despite safety concerns about ESAs in both the ESRD and cancer populations, the proportion of hemodialysis patients with cancer who used ESAs between 2000 and 2011 remained extremely high. EPO dose and hemoglobin levels increased and then decreased. Iron use, iron dose, and transfusions increased substantially. Future research examining the risk-benefit profile of different anemia management strategies in the dialysis population with cancer is needed.