James B. Wetmore

Background: Guidelines favor arteriovenous (AV) access over central venous catheters (CVCs) for hemodialysis due in part to lower infection risk. Nevertheless, most patients initiate hemodialysis with a CVC. We used US Renal Data System data to evaluate whether the comparative mortality risk of these vascular access strategies has changed over time among patients with incident kidney failure. Methods: In this observational study, we evaluated community-dwelling, functionally independent adults (aged 18–85 years) initiating hemodialysis with a CVC in 2013–2022, excluding those with a maturing AV access to prevent immortal time bias. We used the clone-censor-weighting approach, a causal inference method for evaluating dynamic treatment patterns, to compare continuous CVC use versus transition to an AV access. Inverse-probability-of-censoring weighted discrete-time pooled logistic regression modeled the 18-month cumulative risk of death by hemodialysis initiation year, with modality changes treated as competing events. Results: Among 536,836 incident patients, 71,443 and 63,875 deaths occurred in the CVC and AV access groups, respectively. From 2013 to 2022, the adjusted 18-month cumulative risk of death declined from 26.8% to 21.3% in the CVC group, and from 20.9% to 17.1% in the AV access group. Correspondingly, the absolute risk difference comparing CVC versus AV access attenuated by nearly 30% (from 5.9 [95% CI 5.4, 6.3] to 4.2 [95% CI 3.9, 4.5] deaths per 100 patients), whereas the relative risk declined by 3% (from 1.28 [95% CI 1.26, 1.30] to 1.25 [95% CI 1.23, 1.27]). Bloodstream infection-related deaths showed similar declining risk patterns, with a proportionally larger attenuation in absolute risk difference and a greater decline in relative risk between groups. Conclusions: Mortality rates declined among patients initiating hemodialysis with a CVC over the past decade, which has led to a reduction in the absolute excess risk associated with continued CVC use.

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People with hemodialysis-dependent kidney failure have a high incidence of cardiovascular morbidity and mortality, the etiologies of which remain incompletely understood. Recent work has suggested that the hemodialysis procedure itself induces transient episodes of myocardial contractile dysfunction, a phenomenon known as intradialytic myocardial stunning (IDMS). IDMS likely results in repetitive injury to the heart and, as such, may be an underappreciated risk factor which at least partly underlies the high rate of cardiovascular events in this population. However, many important questions about IDMS remain. In this article, we review the evidence base on IDMS. First, we provide a proposed working definition of this entity, placing it within the historical context of other syndromes of transient myocardial contractile abnormalities such as those caused by ischemia or by neurogenic (stress) cardiomyopathy. We then outline the seminal evidence supporting the hypothesis that IDMS is a specific form of Takotsubo (stress) cardiomyopathy. We next discuss the epidemiology of IDMS, including incidence, risk factors, sequelae, and potential contributions to the development of cardiovascular disease in people receiving maintenance hemodialysis. Finally, we focus on the frontiers of IDMS research by identifying avenues of future study, including potential mechanisms which can be investigated using novel techniques, and identify gaps in the current understanding of IDMS which provide a roadmap for future studies.

Background: Ascertaining the clinical relevance of reduced eGFR in older adults is challenging, particularly in those who may have decreased creatinine due to low muscle mass. This study investigated the potential of gait speed and grip strength (markers of muscle mass) to support the clinical interpretation of eGFR and its association with disability-free survival in older adults. Methods: This was a cohort study of the ASPirin in Reducing Events in the Elderly (ASPREE) randomized trial and the ASPREE-eXtension observational follow-up study. Participants were recruited from community-based clinics. ASPREE enrolled adults aged ≥70 years, with African American and Hispanic adults eligible from age ≥65 years, all of whom were free of significant co-morbidity at baseline. Baseline eGFR categories (2 ) combined with gait speed (2 and slow gait’ or ‘eGFR 60-79mL/min/1.73m ² and not weak’. Results: There were 16,925 participants, median follow-up was 8.4 years (interquartile range [IQR]:2.7,9.6), mean age was 75.0±4.5 years, and median eGFR was 79mL/min (IQR:68,89). In the presence of normal gait speed or grip strength, eGFR 2 did not increase the risk for disability-free survival or its components. Slow gait or weak grip accompanying any eGFR was associated with reduced disability-free survival, increased mortality, or increased disability. E.g: participants with eGFR ≥80mL/min/1.73m ² and slow gait were at risk for dementia (HR:1.48, 95%CI:1.23-1.79). Conclusions: In older, initially healthy adults, assessment of gait speed and grip strength may provide additional context when examining associations between eGFR and disability-free survival and its individual components.

Background: Legalization of cannabis across several US states may increase its use by individuals on hemodialysis, particularly among those with chronic pain. Contemporary data on frequency or factors associated with cannabis use by this population are limited. Methods: We conducted a secondary analysis of the HOPE Consortium Trial to Reduce Pain and Opioid Use in Hemodialysis, a randomized trial that tested whether a cognitive behavioral therapy intervention lowered pain interference in people with chronic pain receiving hemodialysis at 103 US dialysis facilities. We analyzed baseline demographic characteristics, social and medical history, pain intensity, pain interference, and cannabis use. Multivariable logistic regression was used to examine associations of baseline data with cannabis use. Linear regression was used to examine whether cannabis use modified the response to the intervention. Results: Among 643 participants, 102 (16%) reported current cannabis use, 133 (21%) reported former use, and 408 (63%) had never used. Current users were younger than never or past users combined (median age 54 vs. 63 years) and more likely to be disabled (79% vs. 66%), to have received dialysis for >5 years (40% vs. 30%), and to self-report depression (41% vs. 31%), anxiety (28% vs. 20%), or any psychological disorder (51% vs. 38%), and less likely to be married (16% vs. 34%). Current cigarette smoking (odds ratio [OR]=3.22, 95% confidence interval (CI) 1.61-6.46) and alcohol use (OR=2.82, 95% CI 1.37-5.80) were independently associated with cannabis use, as were age, relationship status, neighborhood segregation index, and cocaine/heroin use. Cannabis use did not modify response to the intervention. Conclusions: Current cannabis use was reported by 16% of HOPE participants and was more common among younger, unmarried individuals who use other substances , but did not alter response to our intervention. More research is needed on the consequences of cannabis use among people receiving hemodialysis.

BACKGROUND: The ability of the American Heart Association Predicting Risk of Cardiovascular Disease Events (PREVENT) calculator to accurately assign 10-year atherosclerotic cardiovascular disease (ASCVD) risk in older individuals, including those aged ≥80 years, is unknown. This study compares PREVENT with the 2013 Pooled Cohort Equation (PCE) calculator for predicting 10-year ASCVD risk in a large cohort of older adults. METHODS: This was a prospective cohort study of adults without CVD from Australia and the United States aged ≥70 years (≥65 years, if US minorities). They were enrolled from 2010 to 2014 in the ASPREE trial (Aspirin in Reducing Events in the Elderly), a 5-year randomized trial of low-dose aspirin in community-dwelling older adults with posttrial observational follow-up extending to 2022. ASCVD events were adjudicated by expert panels. The discriminative ability of the 2 risk calculators was assessed by Harell C statistic following Cox regression in the 65- to 79-year age group and >80-year age group, separately. For calibration, predicted event numbers were calculated using PREVENT and PCE, scaled for the actual length of follow-up, and compared with the number of observed events in-trial and during extended follow-up. RESULTS: Among the 15 510 participants aged 65 to 79 years (median age, 73.2 years; 56.1% women), 1084 ASCVD events occurred (median follow-up, 8.3 years); PCE predicted 3102 events while PREVENT predicted 1290 events. For the 2787 participants ≥80 years (median age, 82.6 years; 59.2% women), 355 ASCVD events occurred (median follow-up, 7.4 years); PCE predicted 1067 events while PREVENT predicted 350 events. PREVENT showed superior discriminative performance compared with PCE (PREVENT versus PCE, C statistic, 0.793 versus 0.740; P P <0.001 in those aged ≥80 years). CONCLUSIONS: The PREVENT risk calculator is superior to the PCE calculator in predicting ASCVD events in older adults from the United States and Australia, including those aged ≥80 years. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01038583. URL: https://www.isrctn.com ; Unique identifier: ISRCTN83772183.

Background: Development of atrial fibrillation (AF) portends an increased risk of adverse cardiovascular outcomes. Relatively little is known about the longitudinal association between urine albumin excretion and the development of AF, particularly among generally healthy older individuals. Methods: In a post hoc analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, we utilized a marginal structural model to quantify the relationship between annual urine albumin:creatinine ratio (UACR) measurements and new-onset AF. Two approaches were used for handling missing data: one utilized multiple imputation and the other used only cases in whom complete information at baseline was available coupled with last observation carried forward for missing data after baseline. Results: UACR data were available for 19 114 participants (mean age 75.1 ± 4.5 years, 56.4% female, 91.3% White). The median follow-up was 4.7 years. UACR values were low: mean UACR was 2.1 ± 8.2 mg/mmol at baseline and 2.1 ± 3.3 mg/mmol at year 7. AF developed in 941 individuals. The rate of AF development was 1.11/100 person-years among participants with UACR <3 mg/mmol at baseline and 1.74/100 person-years among participants with UACR ≥3 mg/mmol at baseline. After adjustment for a broad range of factors, the hazard ratio for new-onset AF was 1.16 [95% confidence interval (CI) 1.11–1.21] when multiple imputation was used and 1.15 (95% CI 1.10–1.19) when only cases with complete baseline information were used. Conclusions: In older individuals who had low levels of albuminuria, doubling of UACR was associated with a 16% increase in the risk of new-onset AF.

How symptoms recorded in the electronic health record change during the transition to dialysis has not been fully explored. We used the Optum deidentified Integrated Claims–Clinical dataset to identify individuals with CKD stages 4 or 5 who transitioned to dialysis. We searched structured data elements from clinical notes, identified by natural language processing, for symptoms recorded across weekly intervals in the 6 months before and after dialysis initiation and estimated changes in the odds of a symptom being recorded with an interrupted time series analysis using segmented logistic regression. The cohort comprised 728 individuals (aged 68±13 years, 44% women, 56% White, 30% Black). Before dialysis initiation, 83% were recorded as having pain, 68% fatigue/weakness, 66% shortness of breath, 61% nausea/vomiting, and 37% difficulty concentrating. Before dialysis initiation, odds of pain being recorded increased (slope: odds ratio [OR] 1.02 per week, 95% confidence interval [CI], 1.01 to 1.03); initiation was associated with a decrease (intercept change: OR 0.70, 95% CI, 0.59 to 0.82). After initiation, odds of pain were unchanged (postdialysis slope: OR 1.00 per week, 95% CI, 0.99 to 1.01), although this represented an improved trajectory relative to the predialysis period (change in slope: OR 0.98 per week, 95% CI, 0.96 to 0.99). For fatigue/weakness, odds increased before initiation (OR 1.03 per week, 95% CI, 1.02 to 1.04) but decreased on initiation (OR 0.62, 95% CI, 0.51 to 0.75) and thereafter (OR 0.98 per week, 95% CI, 0.97 to 0.99), representing a reduction in slope (OR 0.95 per week, 95% CI, 0.94 to 0.97). Patterns for shortness of breath, nausea/vomiting, and difficulty concentrating were similar to those of pain. Thus, the odds of five key symptoms being recorded in the electronic health record increased over time in the 6 months before dialysis initiation, decreased immediately on initiation, and, generally, remained unchanged in the 6 months thereafter.