The Marginal Cost of Frailty Among Medicare Patients on Hemodialysis.

Introduction:Dialysis patients incur disproportionately high costs compared with other Medicare beneficiaries. Care for frail individuals may be even more costly. We examined the extent to which frailty contributes to higher costs among dialysis patients. Methods:We used ACTIVE/ADIPOSE (A Cohort to Investigate the Value of Exercise/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD) enrollees (adult hemodialysis patients evaluated from June 2009 to August 2011) in a retrospective cohort analysis. Individuals using Medicare as the primary payer were included. Fried's frailty phenotype was evaluated at baseline, 12, and 24 months. Costs were derived from linkage with the US Renal Data System (USRDS) and Medicare claims data. We used generalized estimating equations (GEEs) incorporating time-updated frailty and costs to evaluate adjusted point estimates and the marginal cost associated with being frail. We also investigated if frail patients who died during the study incurred higher costs than those who survived. Results:Among 771 enrollees in ACTIVE/ADIPOSE, 425 met inclusion criteria. Mean age was 56 ± 13 years, body mass index (BMI) 29.2 ± 7.1 kg/m2, 42.4% were women, and 29.0% were frail at baseline. Over a mean follow-up of 2.3 years, frail individuals incurred 22% (95% confidence interval [CI] 9.6%-35.8%) higher costs compared with nonfrail individuals ($87,600 per patient per year [pppy], 95$71,800 pppy, 95% CI 64,800-79,600), the difference was driven primarily by higher inpatient expenditures. The difference between frail and nonfrail patients' inpatient expenditures was even more pronounced among those who died during the study compared with those who survived. Conclusions:Frail dialysis patients incur a significantly higher cost relative to their nonfrail counterparts, primarily driven by higher inpatient costs. Frail patients near end of life incur even higher costs

Effect of a pedometer-based walking intervention on body composition in patients with ESRD: a randomized controlled trial.

BackgroundA randomized trial of a pedometer-based intervention with weekly activity goals led to a modest increase in step count among dialysis patients. In a secondary analysis, we investigated the effect of this intervention on body composition.MethodsSixty dialysis patients were randomized to standard care or a 6-month program consisting of 3 months of pedometers and weekly step count targets and 3 months of post-intervention follow-up. We obtained bioelectrical impedance spectroscopy (BIS) data on 54 of these patients (28 control, 26 intervention) and used linear mixed-modeling (adjusted for sex and dialysis modality) to estimate differences in change in total-body muscle mass (TBMM) adjusted for height2, fat mass (kg), and body mass index (BMI) (kg/m2) between control and intervention groups.ResultsThe median age of participants was 57.5 years (53-66), and 76% were men. At baseline, there was no significant difference between groups in age, BMI, race, or body composition, but there were more men in the intervention group. After 3 months, patients in the intervention group increased their average daily steps by 2414 (95% CI 1047, 3782) more than controls (p < 0.001), but there were no significant differences in body composition. However, at 6 months, participants in the intervention had a significantly greater increase from baseline in TBMM of 0.7 kg/m2 (95% CI 0.3, 1.13), decrease in fat mass (- 4.3 kg [95% CI -7.1, - 1.5]) and decrease in BMI (- 1.0 kg/m2 [95% CI -1.8, - 0.2]) relative to controls. In post-hoc analysis, each increase of 1000 steps from 0 to 3 months was associated with a 0.3 kg decrease in fat mass (95% CI 0.05, 0.5) from 0 to 6 months, but there was no dose-response relationship with TBMM/ht2 or BMI.ConclusionA pedometer-based intervention resulted in greater decreases in fat mass with relative preservation of muscle mass, leading to a greater decrease in BMI over time compared with patients not in the intervention. These differences were driven as much by worsening in the control group as by improvement in the intervention group. Step counts had a dose-response relationship with decrease in fat mass.Trial registrationClinicalTrials.gov (NCT02623348). 02 December 2015

Use of Antihypertensive Agents and Association With Risk of Adverse Outcomes in Chronic Kidney Disease: Focus on Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers.

Background Our objective was to determine patterns of antihypertensive agent use by stage of chronic kidney disease (CKD) and to evaluate the association between different classes of antihypertensive agents with nonrenal outcomes, especially in advanced CKD . Methods and Results We studied 3939 participants of the CRIC (Chronic Renal Insufficiency Cohort) study. Predictors were time-dependent angiotensin-converting enzyme inhibitor or angiotensin receptor blocker , β-blocker, and calcium channel blocker use (versus nonuse of agents in each class). Outcomes were adjudicated heart failure events or death. Adjusted Cox models were used to determine the association between predictors and outcomes. We also examined whether the associations differed based on the severity of CKD (early [stage 2-3 CKD ] versus advanced disease [stage 4-5 CKD ]). During median follow-up of 7.5 years, renin-angiotensin-aldosterone system inhibitor use plateaued during CKD stage 3 (75%) and declined to 37% by stage 5, while β-blocker, calcium channel blocker, and diuretic use increased steadily with advancing CKD . Renin-angiotensin-aldosterone system inhibitor use was associated with lower risk of heart failure (hazard ratio, 0.79; 95% confidence interval, 0.67-0.97) and death (hazard ratio, 0.78; 95% confidence interval, 0.67-0.90), regardless of severity of CKD . Calcium channel blocker use was not associated with risk of heart failure or death, regardless of the severity of CKD . β-Blocker use was associated with higher risk of heart failure (hazard ratio, 1.62; 95% confidence interval, 1.29-2.04) and death (hazard ratio, 1.22; 95% confidence interval, 1.03-1.43), especially during early CKD ( P<0.05 for interaction). Conclusions Angiotensin-converting enzyme inhibitor and angiotensin receptor blocker use decreased, while use of other agents increased with advancing CKD . Use of agents besides angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be associated with suboptimal outcomes in patients with CKD

Timing of preemptive vascular access placement: do we understand the natural history of advanced CKD?: an observational study

BACKGROUND: Little is known about the targets and expectations of practicing nephrologists with regard to timing of preemptive AV access surgery and how these relate to actual observed practice patterns in clinical care. METHODS: We administered a 8-question survey to assess nephrologists’ expectations for preemptive vascular access placement to 53 practicing nephrologists in California. We performed a retrospective chart review of 116 patients who underwent preemptive vascular access placement at a large academic medical center and examined progression to ESRD. RESULTS: According to our survey of nephrologists, most aimed to have preemptive vascular access created about 6 months prior to start of ESRD or when the chances of ESRD within the next year is two-thirds or greater. The estimated GFR level at which they believe match these conditions is approximately 18 ml/min/1.73 m(2). Among the 116 patients with CKD who underwent preemptive vascular access creation, the mean estimated GFR at the time of access creation was 16.1 (6.8) ml/min/1.73 m(2). Only 57 out of the 116 patients (49.1%) patients initiated maintenance HD within 1 year after surgery. CONCLUSIONS: In our study, most nephrologists aim for preemptive vascular access surgery approximately 6 months prior to the start of HD. However in fact, only approximately 50% of patients who underwent preemptive vascular access surgery started HD within 1 year. Better tools are needed to predict the natural history of advanced CKD

CHILI: Chemically-Informed Large-scale Inorganic Nanomaterials Dataset for Advancing Graph Machine Learning

Advances in graph machine learning (ML) have been driven by applications in chemistry as graphs have remained the most expressive representations of molecules. While early graph ML methods focused primarily on small organic molecules, recently, the scope of graph ML has expanded to include inorganic materials. Modelling the periodicity and symmetry of inorganic crystalline materials poses unique challenges, which existing graph ML methods are unable to address. Moving to inorganic nanomaterials increases complexity as the scale of number of nodes within each graph can be broad ($10$ to $10^5$). The bulk of existing graph ML focuses on characterising molecules and materials by predicting target properties with graphs as input. However, the most exciting applications of graph ML will be in their generative capabilities, which is currently not at par with other domains such as images or text. We invite the graph ML community to address these open challenges by presenting two new chemically-informed large-scale inorganic (CHILI) nanomaterials datasets: A medium-scale dataset (with overall >6M nodes, >49M edges) of mono-metallic oxide nanomaterials generated from 12 selected crystal types (CHILI-3K) and a large-scale dataset (with overall >183M nodes, >1.2B edges) of nanomaterials generated from experimentally determined crystal structures (CHILI-100K). We define 11 property prediction tasks and 6 structure prediction tasks, which are of special interest for nanomaterial research. We benchmark the performance of a wide array of baseline methods and use these benchmarking results to highlight areas which need future work. To the best of our knowledge, CHILI-3K and CHILI-100K are the first open-source nanomaterial datasets of this scale -- both on the individual graph level and of the dataset as a whole -- and the only nanomaterials datasets with high structural and elemental diversity.Comment: 16 pages, 15 figures, 8 tables. Dataset is available at https://github.com/UlrikFriisJensen/CHIL

Time- and exercise-dependent gene regulation in human skeletal muscle

BACKGROUND: Skeletal muscle remodeling is a critical component of an organism's response to environmental changes. Exercise causes structural changes in muscle and can induce phase shifts in circadian rhythms, fluctuations in physiology and behavior with a period of around 24 hours that are maintained by a core clock mechanism. Both exercise-induced remodeling and circadian rhythms rely on the transcriptional regulation of key genes. RESULTS: We used DNA microarrays to determine the effects of resistance exercise (RE) on gene regulation in biopsy samples of human quadriceps muscle obtained 6 and 18 hours after an acute bout of isotonic exercise with one leg. We also profiled diurnal gene regulation at the same time points (2000 and 0800 hours) in the non-exercised leg. Comparison of our results with published circadian gene profiles in mice identified 44 putative genes that were regulated in a circadian fashion. We then used quantitative PCR to validate the circadian expression of selected gene orthologs in mouse skeletal muscle. CONCLUSIONS: The coordinated regulation of the circadian clock genes Cry1, Per2, and Bmal1 6 hours after RE and diurnal genes 18 hours after RE in the exercised leg suggest that RE may directly modulate circadian rhythms in human skeletal muscle

Novel Anemia Therapies in CKD: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Anemia is common in patients with chronic kidney disease (CKD) and is associated with a high burden of morbidity and adverse clinical outcomes. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline for the diagnosis and management of anemia in CKD. Since then, new data from studies assessing established and emerging therapies for the treatment of anemia and iron deficiency have become available. Beginning in 2019, KDIGO planned two Controversies Conferences to review the new evidence and its potential impact on the management of anemia in clinical practice. Here we report on the second of these conferences held virtually in December 2021 which focused on a new class of agents, the hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs). This report provides a review of the consensus points and controversies from this second conference and highlights areas that warrant prioritization for future research

The ASCEND-NHQ trial found positive effects of daprodustat on hemoglobin and quality of life in patients with non-dialysis-dependent chronic kidney disease

The ASCEND-NHQ trial evaluated the effects of daprodustat on hemoglobin and the Medical Outcomes Study 36-item Short Form Survey (SF-36) Vitality score (fatigue) in a multicenter, randomized, double-blind, placebo-controlled trial. Adults with chronic kidney disease (CKD) Stages 3-5, hemoglobin 8.5-10.0 g/dl, transferrin saturation 15% or more, and ferritin 50 ng/ml or more without recent erythropoiesis-stimulating agent use were randomized (1:1) to oral daprodustat or placebo to achieve and maintain target hemoglobin of 11-12 g/dl over 28 weeks. The primary endpoint was the mean change in hemoglobin between baseline and the evaluation period (Weeks 24-28). Principal secondary endpoints were proportion of participants with a 1 g/dl or more increase in hemoglobin and mean change in the vitality score between baseline and Week 28. Outcome superiority was tested (one-sided alpha level of 0.025) among 614 randomized participants. The adjusted mean change in hemoglobin from baseline to the evaluation period was greater with daprodustat (1.58 vs 0.19 g/dl). The adjusted mean treatment difference (AMD) was significant at 1.40 g/dl (95% confidence interval 1.23, 1.56). A greater proportion of participants receiving daprodustat showed a significant 1 g/dl or more increase in hemoglobin from baseline (77% vs 18%). The mean SF-36 Vitality score increased by 7.3 and 1.9 points with daprodustat and placebo, respectively; a significant 5.4 point Week 28 ADM increase. Adverse event rates were similar (69% vs 71%); relative risk 0.98, (95% confidence interval 0.88, 1.09). Thus, in participants with CKD Stages 3-5, daprodustat resulted in a significant increase in hemoglobin and improvement in fatigue without an increase in the overall frequency of adverse events