Microalbuminuria, peripheral artery disease, and cognitive function

Kidney disease may be linked to a decline in cognitive activity. We examined the association of microalbuminuria and cognitive function in a general population of older adults in the United States drawn from the National Health and Nutrition Examination Survey of 1999–2002. Cognitive function was measured by digit symbol substitution in 2386 participants 60 years of age and older of whom 448 had microalbuminuria. Covariates included age, gender, race/ethnicity, education, smoking, diabetes, and hypertension. Among participants with peripheral artery disease, those with microalbuminuria had a significantly lower cognitive function score compared to those with a normal albumin-to-creatinine ratio. The association between microalbuminuria and cognitive function was weak in those without peripheral artery disease. But in those with peripheral artery disease, the odds of microalbuminuria associated with cognitive function in the lowest and middle tertiles was 6.5 and 3.5, respectively

The comparative risk of acute kidney injury of vancomycin relative to other common antibiotics

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

Primary prevention of chronic kidney disease through population-based strategies for blood pressure control: The ARIC study

While much of the chronic kidney disease (CKD) literature focuses on the role of blood pressure reduction in delaying CKD progression, little is known about the benefits of modest population-wide decrements in blood pressure on incident CKD. The authors used multivariable linear regression to characterize the impact on incident CKD of two approaches for blood pressure management: (1) a 1-mm Hg reduction in systolic BP across the entire study population; and (2) a 10% reduction in participants with unaware, untreated, and uncontrolled BP above goal as defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) thresholds. Over a mean of 20 years of follow-up (ARIC [Atherosclerosis Risk in Communities] study, n = 15 390), 3852 incident CKD events were ascertained. After adjustment, a 1-mm Hg decrement in systolic BP across the population was associated with an estimated 11.7 (95% confidence interval [CI], 6.2–17.3) and 13.4 (95% CI, 10.3–16.6) fewer CKD events per 100 000 person-years in blacks and whites, respectively. Among participants with BP above JNC 7 goal, a 10% decrease in unaware, untreated, or uncontrolled BP was associated with 3.2 (95% CI, 2.0–4.9), 2.8 (95% CI, 1.8–4.3), and 5.8 (95% CI, 3.6–8.8) fewer CKD events per 100 000 person-years in blacks and 3.1 (95% CI, 2.3–4.1), 0.7 (95% CI, 0.5–0.9), and 1.0 (95% CI, 1.3–2.4) fewer CKD events per 100 000 person-years in whites. Modest population-wide reductions in systolic BP hold potential for the primary prevention of CKD

Safety of dynamic intravenous iron administration strategies in hemodialysis patients

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

The association of retinopathy and low GFR in type 2 diabetes

We sought to determine characteristics which strengthen the association between markers of diabetic kidney disease and retinopathy

Influenza vaccine effectiveness in patients on hemodialysis: An analysis of a natural experiment

Background Although the influenza vaccine is recommended for patients with end-stage renal disease, little is known about its effectiveness. Observational studies of vaccine effectiveness (VE) are challenging because vaccinated subjects may be healthier than unvaccinated subjects. Methods Using US Renal Data System data, we estimated VE for influenza-like illness, influenza/pneumonia hospitalization, and mortality in adult patients undergoing hemodialysis by using a natural experiment created by the year-to-year variation in the match of the influenza vaccine to the circulating virus. We compared vaccinated patients in matched years (1998, 1999, and 2001) with a mismatched year (1997) using Cox proportional hazards models. Ratios of hazard ratios compared vaccinated patients between 2 years and unvaccinated patients between 2 years. We calculated VE as 1 − effect measure. Results Vaccination rates were less than 50% each year. Conventional analysis comparing vaccinated with unvaccinated patients produced average VE estimates of 13%, 16%, and 30% for influenza-like illness, influenza/pneumonia hospitalization, and mortality, respectively. When restricted to the preinfluenza period, results were even stronger, indicating bias. The pooled ratio of hazard ratios comparing matched seasons with a placebo season resulted in a VE of 0% (95% CI, −3% to 2%) for influenza-like illness, 2% (−2% to 5%) for hospitalization, and 0% (−3% to 3%) for death. Conclusions Relative to a mismatched year, we found little evidence of increased VE in subsequent well-matched years, suggesting that the current influenza vaccine strategy may have a smaller effect on morbidity and mortality in the end-stage renal disease population than previously thought. Alternate strategies (eg, high-dose vaccine, adjuvanted vaccine, and multiple doses) should be investigated

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

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) < 60 mL/min/1.73 m2 or urine albumin-creatinine ratio ≥ 25 mg/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

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

<p><b><i>Background:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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; <i>p</i> value = 0.04). <b><i>Conclusion:</i></b> 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.</p