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      Circulating Endotoxaemia and Frequent Haemodialysis Schedules

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          Abstract

          Background/Aims: Endotoxaemia, a driver of systemic inflammation, appears to be driven by dialysis-induced circulatory stress in haemodialysis (HD) patients. More frequent HD regimens are associated with lower ultrafiltration requirements, improved haemodynamic stability and lower systemic inflammation. This study investigated the hypothesis that more frequently dialysed patients, with reduced exposure to dialysis-induced haemodynamic perturbation, would have lower circulating endotoxin (ET) levels. Methods: A cross-sectional study of86 established HD patients compared three groups: conventional HD 3× per week (HD3, n = 56), frequent HD 5-6× per week (SDHD, n = 20), and nocturnal HD (NHD, n = 10). Data collection included ultrafiltration volume and rate, serial blood pressures and blood sampling with quantification of ET, troponin T and high-sensitivity CRP (hsCRP). Results: Pre-dialysis serum ET was highest in the conventional HD group (HD3 0.66 ± 0.29 EU/ml vs. NHD 0.08 ± 0.04 EU/ml). Across the study population, severity of endotoxaemia was associated with higher ultrafiltration rates, degree of intradialytic hypotension, troponin T and hsCRP levels. NHD patients had the lowest ultrafiltration requirements, the greatest haemodynamic stability and lower ET levels. Conclusion: More frequent HD regimens are associated with lower levels of circulating ET compared with conventional HD. Reduced ET translocation may be related to the greater haemodynamic stability of these treatments, with superior maintenance of splanchnic perfusion.

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          Hemodialysis-induced cardiac injury: determinants and associated outcomes.

          Hemodialysis (HD)-induced myocardial stunning driven by ischemia is a recognized complication of HD, which can be ameliorated by HD techniques that improve hemodynamics. In nondialysis patients, repeated ischemia leads to chronic reduction in left ventricular (LV) function. HD may initiate and drive the same process. In this study, we examined the prevalence and associations of HD-induced repetitive myocardial injury and long-term effects on LV function and patient outcomes. Seventy prevalent HD patients were assessed for evidence of subclinical myocardial injury at baseline using serial echocardiography and followed up after 12 mo. Intradialytic blood pressure, hematologic and biochemical samples, and patient demographics were also collected at both time points. Sixty-four percent of patients had significant myocardial stunning during HD. Age, ultrafiltration volumes, intradialytic hypotension, and cardiac troponin-T (cTnT) levels were independent determinants associated with its presence. Myocardial stunning was associated with increased relative mortality at 12 mo (P = 0.019). Cox regression analysis showed increased hazard of death in patients with myocardial stunning and elevated cTnT than in patients with elevated cTnT alone (P < 0.02). Patients with myocardial stunning who survived 12 mo had significantly lower LV ejection fractions at rest and on HD (P < 0.001). HD-induced myocardial stunning is common, and may contribute to the development of heart failure and increased mortality in HD patients. Enhanced understanding of dialysis-induced cardiac injury may provide novel therapeutic targets to reduce currently excessive rates of cardiovascular morbidity and mortality.
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            Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease.

            Translocated endotoxin derived from intestinal bacteria has a wide range of adverse effects on cardiovascular (CV) structure and function, driving systemic inflammation, atherosclerosis and oxidative stress. This study's aim was to investigate endotoxemia across the spectrum of chronic kidney disease (CKD). Circulating endotoxin was measured in 249 patients comprising CKD stage 3 to 5 and a comparator cohort of hypertensive patients without significant renal impairment. Patients underwent extended CV assessment, including pulse wave velocity and vascular calcification. Hemodialysis (HD) patients also received detailed echocardiographic-based intradialytic assessments. Patients were followed up for 1 year to assess survival. Circulating endotoxemia was most notable in those with the highest CV disease burden (increasing with CKD stage), and a sharp increase was observed after initiation of HD. In HD patients, predialysis endotoxin correlated with dialysis-induced hemodynamic stress (ultrafiltration volume, relative hypotension), myocardial stunning, serum cardiac troponin T, and high-sensitivity C-reactive protein. Endotoxemia was associated with risk of mortality. CKD patients are characteristically exposed to significant endotoxemia. In particular, HD-induced systemic circulatory stress and recurrent regional ischemia may lead to increased endotoxin translocation from the gut. Resultant endotoxemia is associated with systemic inflammation, markers of malnutrition, cardiac injury, and reduced survival. This represents a crucial missing link in understanding the pathophysiology of the grossly elevated CV disease risk in CKD patients, highlighting the potential toxicity of conventional HD and providing a novel set of potential therapeutic strategies to reduce CV mortality in CKD patients.
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              Congestive heart failure in dialysis patients: prevalence, incidence, prognosis and risk factors.

              Cardiovascular disease is the most common cause of death in dialysis subjects. Congestive heart failure (CHF) is a common presenting symptom of cardiovascular disease in the dialysis population. Information regarding prevalence, incidence, risk factors and prognosis is crucial for planning rational interventional studies. A prospective multicenter cohort study of 432 dialysis patients followed for a mean of 41 months was carried out. Prospective information on a variety of risk factors was collected. Annual echocardiography and clinical assessment was performed. Major endpoints included death and the development of morbid cardiovascular events. One hundred and thirty-three (31%) subjects had CHF at the time of initiation of dialysis therapy. Multivariate analysis showed that the following risk factors were significantly and independently associated with CHF at baseline: systolic dysfunction, older age, diabetes mellitus and ischemic heart disease. Seventy-six of 299 subjects (25%) who did not have baseline CHF subsequently developed CHF during their course on dialysis. Compared to those subjects who never developed CHF (N = 218) multivariate analysis identified the following risk factors for the development of CHF: older age, anemia during dialysis therapy, hypoalbuminemia, hypertension during dialysis therapy, and systolic dysfunction. Seventy-five of the 133 (56%) subjects with CHF at baseline had recurrent CHF during follow-up. Independent and significant risk factors for CHF recurrence were ischemic heart disease and systolic dysfunction, anemia during dialysis therapy and hypoalbuminemia. The median survival of subjects with CHF at baseline was 36 months compared to 62 months in subjects without CHF. In this study the prevalence of CHF on starting ESRD therapy and the subsequent annual incidence was high.(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2014
                December 2014
                12 November 2014
                : 128
                : 1-2
                : 141-146
                Affiliations
                aDepartment of Renal Medicine, Royal Derby Hospital, and bUniversity of Nottingham, Derby, UK; cMedicine &amp; Therapeutics, Chinese University of Hong Kong, Hong Kong, SAR, China; dSatellite Healthcare, Inc., Mountain View, Calif., and eDepartment of Nephrology, Stanford University, Palo Alto, Calif., USA
                Author notes
                *Prof. C.W. McIntyre, Kidney Clinical Research Unit, London Health Sciences Centre, London, ON, N6G 2S5 (Canada), E-Mail cmcint48@uwo.ca
                Article
                366519 Nephron Clin Pract 2014;128:141-146
                10.1159/000366519
                25401768
                7af9eee8-0bf2-4a8b-adb1-e2a1e2446b54
                © 2014 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.

                History
                : 17 January 2014
                : 04 August 2014
                Page count
                Figures: 2, Tables: 1, Pages: 6
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Endotoxin,Frequent dialysis,Quotidian dialysis,Chronic kidney disease,Haemodialysis,Nocturnal dialysis,Inflammation,Ischaemia,Circulatory stress

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