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      Frailty Prevalence in Younger End-Stage Kidney Disease Patients Undergoing Dialysis and Transplantation

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          Abstract

          Background: Frailty, originally characterized in community-dwelling older adults, is increasingly being studied and implemented for adult patients with end-stage kidney disease (ESKD) of all ages (>18 years). Frailty prevalence and manifestation are unclear in younger adults (18–64 years) with ESKD; differences likely exist based on whether the patients are treated with hemodialysis (HD) or kidney transplantation (KT). Methods: We leveraged 3 cohorts: 378 adults initiating HD (2008–2012), 4,304 adult KT candidates (2009–2019), and 1,396 KT recipients (2008–2019). The frailty phenotype was measured within 6 months of dialysis initiation, at KT evaluation, and KT admission. Prevalence of frailty and its components was estimated by age (≥65 vs. <65 years). A Wald test for interactions was used to test whether risk factors for frailty differed by age. Results: In all 3 cohorts, frailty prevalence was higher among older than younger adults (HD: 71.4 vs. 47.3%; candidates: 25.4 vs. 18.8%; recipients: 20.8 vs. 14.3%). In all cohorts, older patients were more likely to have slowness and weakness but less likely to report exhaustion. Among candidates, older age (odds ratio [OR] = 1.79, 95% CI: 1.47–2.17), non-Hispanic black race (OR = 1.30, 95% CI: 1.08–1.57), and dialysis type (HD vs. no dialysis: OR = 2.06, 95% CI: 1.61–2.64; peritoneal dialysis vs. no dialysis: OR = 1.78, 95% CI: 1.28–2.48) were associated with frailty prevalence, but sex and Hispanic ethnicity were not. These associations did not differ by age ( p<sub>interactions</sub> > 0.1). Similar results were observed for recipients and HD patients. Conclusions: Although frailty prevalence increases with age, younger patients have a high burden. Clinicians caring for this vulnerable population should recognize that younger patients may experience frailty and screen all age groups.

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          Most cited references 41

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          Adapting the Charlson Comorbidity Index for use in patients with ESRD.

          Accurate prediction of survival for patients with end-stage renal disease (ESRD) and multiple comorbid conditions is difficult. In nondialysis patients, the Charlson Comorbidity Index has been used to adjust for comorbidity. The purpose of this study is to assess the validity of the Charlson index in incident dialysis patients and modify the index for use specifically in this patient population. Subjects included all incident hemodialysis and peritoneal dialysis patients starting dialysis therapy between July 1, 1999, and November 30, 2000. These 237 patients formed a cohort from which new integer weights for Charlson comorbidities were derived using Cox proportional hazards modeling. Performance of the original Charlson index and the new ESRD comorbidity index were compared using Kaplan-Meier survival curves, change in likelihood ratio, and the c statistic. After multivariate analysis and conversion of hazard ratios to index weights, only 6 of the original 18 Charlson variables were assigned the same weight and 6 variables were assigned a weight higher than in the original Charlson index. Using Kaplan-Meier survival curves, we found that both the original Charlson index and the new ESRD comorbidity index were associated with and able to describe a wide range of survival. However, the new study-specific index had better validated performance, indicated by a greater change in the likelihood ratio test and higher c statistic. This study indicates that the original Charlson index is a valid tool to assess comorbidity and predict survival in patients with ESRD. However, our modified ESRD comorbidity index had slightly better performance characteristics in this population.
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            Frailty assessment instruments: Systematic characterization of the uses and contexts of highly-cited instruments.

            The medical syndrome of frailty is widely recognized, yet debate remains over how best to measure it in clinical and research settings. This study reviewed the frailty-related research literature by (a) comprehensively cataloging the wide array of instruments that have been utilized to measure frailty, and (b) systematically categorizing the different purposes and contexts of use for frailty instruments frequently cited in the research literature. We identified 67 frailty instruments total; of these, nine were highly-cited (≥ 200 citations). We randomly sampled and reviewed 545 English-language articles citing at least one highly-cited instrument. We estimated the total number of uses, and classified use into eight categories: risk assessment for adverse health outcomes (31% of all uses); etiological studies of frailty (22%); methodology studies (14%); biomarker studies (12%); inclusion/exclusion criteria (10%); estimating prevalence as primary goal (5%); clinical decision-making (2%); and interventional targeting (2%). The most common assessment context was observational studies of older community-dwelling adults. Physical Frailty Phenotype was the most used frailty instrument in the research literature, followed by the Deficit Accumulation Index and the Vulnerable Elders Survey. This study provides an empirical evaluation of the current uses of frailty instruments, which may be important to consider when selecting instruments for clinical or research purposes. We recommend careful consideration in the selection of a frailty instrument based on the intended purpose, domains captured, and how the instrument has been used in the past. Continued efforts are needed to study the validity and feasibility of these instruments.
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              Initial manifestations of frailty criteria and the development of frailty phenotype in the Women's Health and Aging Study II.

              Understanding points of onset of the frailty syndrome is vital to early identification of at-risk individuals and to targeting intervention efforts to those components that are first affected, when reversal may be most possible. This study aims to characterize natural history by which commonly used frailty criteria manifest and to assess whether the rate of progression to frailty depends on initial manifestations. The investigation was based on a 7.5-year observational study of 420 community-dwelling women aged 70-79 years who were not frail at baseline, with frailty defined as meeting>or=3 of 5 criteria: weight loss, slow walking speed, weakness, exhaustion, and low physical activity level. The 7.5-year incidence of frailty was 9% among women who were nonfrail at baseline. Despite significant heterogeneity, weakness was the most common first manifestation, and occurrence of weakness, slowness, and low physical activity preceded exhaustion and weight loss in 76% of the women who were nonfrail at baseline. Women with exhaustion or weight loss as initial presenting symptoms were 3-5 times more likely to become frail than were women without any criterion (p<.05). Our findings suggest that weakness may serve as a warning sign of increasing vulnerability in early frailty development, and weight loss and exhaustion may help to identify women most at risk for rapid adverse progression.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2020
                July 2020
                08 July 2020
                : 51
                : 7
                : 501-510
                Affiliations
                aDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
                bDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
                cDivision of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
                dChild Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
                eDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
                fWelch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, USA
                gDepartment of Health, Behavior, and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
                hKidney Health Research Collaborative, Department of Medicine, University of California, San Francisco and Department of Medicine, San Francisco VA Medical Center, San Francisco, California, USA
                iDivision of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
                jDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
                kDivision of Nephrology, Department of Pediatrics and Medicine, The Hospital for Sick Children, University Health Network and University of Toronto, Toronto, Ontario, Canada
                Author notes
                *Mara A. McAdams-DeMarco, Department of Epidemiology, Johns Hopkins School of Public Health, 615 N. Wolfe Street W6033, Baltimore 21205 (USA), mara@jhu.edu
                Article
                508576 Am J Nephrol 2020;51:501–510
                10.1159/000508576
                32640462
                © 2020 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, Tables: 2, Pages: 10
                Categories
                Transplantation: Research Article

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