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      Online hemodiafiltration and mortality risk in end-stage renal disease patients: A critical appraisal of current evidence

      review-article
      Kidney Research and Clinical Practice
      Korean Society of Nephrology
      Chronic kidney failure, Hemodiafiltration, Mortality

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          Abstract

          The life expectancy of end-stage renal disease patients undergoing regular hemodialysis (HD) remains significantly lower than in the general population. Reducing excess mortality by improving renal replacement options is an unmet medical need. Online post-dilution hemodiafiltration (HDF) has been promoted as the gold standard, offering improved clinical outcomes, based on numerous observational studies that suggest a reduced mortality risk and lower morbidity with HDF compared with standard HD. However, most randomized controlled trials (RCTs) have failed to demonstrate a significant beneficial effect of HDF on all-cause mortality. The effects on secondary outcomes were often negligible or absent. Unfortunately, these RCTs were characterized by a moderate to high risk of bias. In post-hoc analyses of the largest RCTs and meta-analysis of individual participant data from four RCTs, HDF patients receiving the highest convection volume consistently and dose-dependently saw superior outcomes. However, as these studies were not designed a priori to clarify this issue, and there are no indisputable mechanisms underlying reduced mortality risks, we cannot exclude the possibility that the health status of patients (with vascular access as a proxy) may affect outcomes more than the convective technique itself. There is currently insufficient evidence to support the contention that high-volume HDF confers relevant benefits to patients over standard HD. The conflicting data of published RCTs reduce confidence in the superiority of high-volume convective therapy. Hopefully, ongoing large RCTs (for example, CONVINCE) may supply an indisputable answer to the crucial question of high-volume HDF.

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          Most cited references21

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          2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials

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            Treatment tolerance and patient-reported outcomes favor online hemodiafiltration compared to high-flux hemodialysis in the elderly.

            Large cohort studies suggest that high convective volumes associated with online hemodiafiltration may reduce the risk of mortality/morbidity compared to optimal high-flux hemodialysis. By contrast, intradialytic tolerance is not well studied. The aim of the FRENCHIE (French Convective versus Hemodialysis in Elderly) study was to compare high-flux hemodialysis and online hemodiafiltration in terms of intradialytic tolerance. In this prospective, open-label randomized controlled trial, 381 elderly chronic hemodialysis patients (over age 65) were randomly assigned in a one-to-one ratio to either high-flux hemodialysis or online hemodiafiltration. The primary outcome was intradialytic tolerance (day 30-day 120). Secondary outcomes included health-related quality of life, cardiovascular risk biomarkers, morbidity, and mortality. During the observational period for intradialytic tolerance, 85% and 84% of patients in high-flux hemodialysis and online hemodiafiltration arms, respectively, experienced at least one adverse event without significant difference between groups. As exploratory analysis, intradialytic tolerance was also studied, considering the sessions as a statistical unit according to treatment actually received. Over a total of 11,981 sessions, 2,935 were complicated by the occurrence of at least one adverse event, with a significantly lower occurrence in online hemodiafiltration with fewer episodes of intradialytic symptomatic hypotension and muscle cramps. By contrast, health-related quality of life, morbidity, and mortality were not different in both groups. An improvement in the control of metabolic bone disease biomarkers and β2-microglobulin level without change in serum albumin concentration was observed with online hemodiafiltration. Thus, overall outcomes favor online hemodiafiltration over high-flux hemodialysis in the elderly.
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              Hemodialysis-induced cardiovascular disease.

              More than half of all deaths among end stage renal disease (ESRD) patients are due to cardiovascular disease (CVD). Cardiovascular changes secondary to renal dysfunction, including fluid overload, uremic cardiomyopathy, secondary hyperparathyroidism, anemia, altered lipid metabolism, and accumulation of gut microbiota-derived uremic toxins like trimethylamine N-oxidase, contribute to the high risk for CVD in the ESRD population. In addition, conventional hemodialysis (HD) itself poses myocardial stress and injury on the already compromised cardiovascular system in uremic patients. This review will provide an overview of cardiovascular changes in chronic kidney disease and ESRD, a description of reported mechanisms for HD-induced myocardial injury, comparison of HD with other treatment modalities in the context of CVD, and possible management strategies.
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                Author and article information

                Journal
                Kidney Res Clin Pract
                Kidney Res Clin Pract
                Kidney Research and Clinical Practice
                Korean Society of Nephrology
                2211-9132
                2211-9140
                June 2019
                30 June 2019
                : 38
                : 2
                : 159-168
                Affiliations
                Department of Internal Medicine IV, Medical Center of the University of Munich, Munich, Germany
                Author notes
                Correspondence: Helmut Schiffl, Department of Internal Medicine IV, Medical Center of the University of Munich, Ziemssenstr. 1, D-80336 München, Germany. E-mail: h-schiffl@ 123456t-online.de

                Edited by Gheun-Ho Kim, Hanyang University College of Medicine, Seoul, Korea

                Author information
                https://orcid.org/0000-0003-0604-6109
                Article
                krcp-38-159
                10.23876/j.krcp.18.0160
                6577208
                31137926
                16876f7f-ab8f-4b89-bf2c-aa26256683e6
                Copyright © 2019 by The Korean Society of Nephrology

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 December 2018
                : 24 February 2019
                : 10 March 2019
                Categories
                Review Article

                chronic kidney failure,hemodiafiltration,mortality
                chronic kidney failure, hemodiafiltration, mortality

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