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      Mortality Risk in Chronic Kidney Disease Patients Transitioning to Dialysis: Impact of Opiate and Non-Opiate Use

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          Abstract

          Background: Population-based studies show there is a high prevalence of chronic kidney disease (CKD) patients suffering from chronic pain. While opiates are frequently prescribed in non-dialysis-dependent CKD (NDD-CKD) patients, there may be toxic accumulation of metabolites, particularly among those progressing to end-stage renal disease (ESRD). We examined the association of opiate versus other analgesic use during the pre-ESRD period with post-ESRD mortality among NDD-CKD patients transitioning to dialysis. Methods: We examined a national cohort of US Veterans with NDD-CKD who transitioned to dialysis over 2007–14. Among patients who received ≥1 prescription(s) in the Veterans Affairs (VA) Healthcare System within 1 year of transitioning to dialysis, we examined associations of pre-ESRD analgesic status, defined as opiate, gabapentin/pregabalin, other non-opiate analgesic, versus no analgesic use, with post-ESRD mortality using multivariable Cox models. Results: Among 57,764 patients who met eligibility criteria, pre-ESRD opiate and gabapentin/pregabalin use were each associated with higher post-ESRD mortality (ref: no analgesic use), whereas non-opiate analgesic use was not associated with higher mortality in expanded case-mix analyses: HRs (95% CIs) 1.07 (1.05–1.10), 1.07 (1.01–1.13), and 1.00 (0.94–1.06), respectively. In secondary analyses, increasing frequency of opiate prescriptions exceeding 1 opiate prescription in the 1-year pre-ESRD period was associated with incrementally higher post-ESRD mortality (ref: no analgesic use). Conclusions: In NDD-CKD patients transitioning to dialysis, pre-ESRD opiate and gabapentin/pregabalin use were associated with higher post-ESRD mortality, whereas non-opiate analgesic use was not associated with death. There was a graded association between increasing frequency of pre-ESRD opiate use and incrementally higher mortality.

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          Most cited references 28

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          Renal provider recognition of symptoms in patients on maintenance hemodialysis.

          Although several studies have found that the burden of symptoms in patients who are on maintenance hemodialysis is substantial, little is known about renal providers' awareness of these symptoms. The aim of this study was to assess renal provider recognition of symptoms and their severity in hemodialysis patients. The Dialysis Symptom Index, a 30-item measure of symptoms and their severity, was administered to patients during a routine hemodialysis session. Immediately after surveying patients, the renal provider who evaluated the patient completed the Dialysis Symptom Index to report the symptoms that he or she believed were present in that patient. Sensitivity, specificity, and positive and negative predictive values of provider reports of symptoms were calculated using patient reports as the reference standard. Patient-provider agreement on the presence and severity of symptoms was assessed using the kappa statistic. Surveys were completed by 75 patients and 18 providers. For 27 of 30 symptoms, the sensitivity of provider responses was <50%, and provider responses for 25 symptoms were characterized by positive predictive values of <75%. kappa scores for 25 symptoms including those pertaining to pain, sexual dysfunction, sleep disturbance, and psychologic distress were <0.20, indicating poor provider recognition of these symptoms. Providers underestimated the severity of 19 of 30 symptoms. Renal providers are largely unaware of the presence and severity of symptoms in patients who are on maintenance hemodialysis. Implementation of a standardized symptom assessment process may improve provider recognition of symptoms and promote use of symptom-alleviating treatments.
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            Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: A systematic review and meta-analysis of observational studies.

            The association between acute kidney injury (AKI) and use of non-steroidal anti-inflammatory drugs (NSAIDs) is well established. However, little is known about the comparative risk of individual NSAIDs, including specific COX-2 inhibitors.
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              Symptoms in advanced renal disease: a cross-sectional survey of symptom prevalence in stage 5 chronic kidney disease managed without dialysis.

              Numbers of patients with stage 5 chronic kidney disease (CKD) managed conservatively (without dialysis) are increasing steadily but prevalence and severity of symptoms in this population are not yet known. To describe symptom prevalence, symptom severity, and total symptom burden in patients with stage 5 CKD managed conservatively. A cross-sectional survey of patients with stage 5 CKD managed conservatively, in three U.K. renal units. Symptoms were assessed using the patient-completed Memorial Symptom Assessment Scale Short Form (MSAS-SF), with additional renal symptoms. Sixty-six patients were recruited (response rate, 62%), with mean age 82 years (standard deviation [SD] +/- 6.6), and mean estimated glomerular filtration rate 11.2 mL/min (SD +/- 2.8). Symptoms reported by more than one third or 33% of patients were (95% confidence intervals shown in parentheses): lack of energy, 76% (66%-84%); pruritus, 74% (65%-82%); drowsiness, 65% (54%-74%); dyspnea, 61% (50%-70%); edema, 58% (47%-66%); pain, 53% (42%-63%); dry mouth, 50% (39%-60%); muscle cramps, 50% (39%-60%); restless legs, 48% (38%-58%); lack of appetite, 47% (37%-58%); poor concentration, 44% (34%-54%); dry skin, 42% (32%-53%); sleep disturbance, 41% (32%-51%); and constipation, 35% (26%-45%). Mean number of symptoms reported on MSAS-SF was 11.58 (SD +/- 5.2), with an additional 2.77 (SD +/- 1.7) renal symptoms. Symptoms were also most severe in the more prevalent symptoms. Pain was an exception, with disproportionately greater severity (32% of all patients reported moderate/severe pain). This study demonstrates that patients with stage 5 CKD have considerable symptom control needs, similar to advanced cancer populations, but with different patterns of individual symptoms and severity, particularly pain. Implications for palliative care, hospice, and nephrology services in planning and providing care are discussed.
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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
                September 2020
                10 August 2020
                : 51
                : 9
                : 715-725
                Affiliations
                aHarold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology, Hypertension and Kidney Transplantation, University of California Irvine, Orange, California, USA
                bTibor Rubin Veterans Affairs Medical Center, Long Beach, California, USA
                cUniversity of Washington School of Public Health, Seattle, Washington, USA
                dKaiser Permanente Southern California, Los Angeles, California, USA
                eDivision of Nephrology, University of Tennessee Health Science Center, Memphis, Tennessee, USA
                fDepartment of Medicine, University of California Irvine, Orange, California, USA
                gDivision of General Internal Medicine, University of California Irvine, Orange, California, USA
                hNephrology Section, Memphis Veterans Affairs Medical Center, Memphis, Tennessee, USA
                Author notes
                *Connie M. Rhee, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, 101 The City Drive South, City Tower, Suite 400, Orange, CA 92868-3217 (USA), crhee1@uci.edu
                Article
                509451 Am J Nephrol 2020;51:715–725
                10.1159/000509451
                32777779
                © 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: 1, Pages: 11
                Categories
                Patient-Oriented, Translational Research: Research Article

                Cardiovascular Medicine, Nephrology

                Analgesic, Dialysis, Mortality, Transition, Opiate

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