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      Effects of Renal Replacement Therapy on Renal Recovery after Acute Kidney Injury

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          Abstract

          Recovery of kidney function following an episode of acute kidney injury (AKI) is now acknowledged as a vital patient-centered outcome with clear health economic implications. In approximately 5-8% of critically ill patients with more severe forms of AKI, support with renal replacement therapy (RRT) is provided. Recent data have suggested that rates of RRT utilization in AKI are increasing. Despite advances in our understanding of how best to prescribe acute RRT in critically ill patients with AKI, additional aspects remain uncertain, predisposing to suboptimal delivery and variation in practice. Importantly, if, when, how, and by what principles we apply acute RRT for AKI are all treatment decision-related factors that are modifiable and may interact with recovery of kidney function. Limited data, mostly from observational studies and secondary analyses, have explored the specific association between acute RRT and recovery. Available data are not able to clarify whether providing any RRT in otherwise eligible patients with AKI impacts recovery. They are also unable to inform whether the timing or circumstance under which RRT is started impacts recovery. No studies have evaluated whether there is an optimal time to start RRT to maximize the probability of recovery. Accumulated evidence, mostly derived from observational studies, suggests initial therapy in critically ill patients with AKI with continuous RRT, compared with intermittent modalities, improves the probability of recovery to dialysis independence. Evidence from high-quality randomized trials failed to show any association between delivered dose intensity of RRT and recovery. The use of biocompatible membranes for acute RRT may improve recovery in AKI; however, data are inconsistent. Limited data have evaluated the impact of membrane flux properties on recovery. Preliminary data have suggested that circuit anticoagulation with citrate, which results in a reduction in membrane-induced oxidative stress and leukocyte activation, may be associated with improved recovery; however, further corroborative data are needed. Additional evidence, ideally from randomized trials, is clearly needed to inform best practice in the delivery of acute RRT to optimize probability of recovery of kidney function for survivors of AKI.

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          Most cited references 43

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          Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts.

          Both a low estimated glomerular filtration rate (eGFR) and albuminuria are known risk factors for end-stage renal disease (ESRD). To determine their joint contribution to ESRD and other kidney outcomes, we performed a meta-analysis of nine general population cohorts with 845,125 participants and an additional eight cohorts with 173,892 patients, the latter selected because of their high risk for chronic kidney disease (CKD). In the general population, the risk for ESRD was unrelated to eGFR at values between 75 and 105 ml/min per 1.73 m(2) but increased exponentially at lower levels. Hazard ratios for eGFRs averaging 60, 45, and 15 were 4, 29, and 454, respectively, compared with an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log ESRD risk without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 30, 300, and 1000 mg/g were 5, 13, and 28, respectively, compared with an albumin-to-creatinine ratio of 5. Albuminuria and eGFR were associated with ESRD, without evidence for multiplicative interaction. Similar associations were found for acute kidney injury and progressive CKD. In high-risk cohorts, the findings were generally comparable. Thus, lower eGFR and higher albuminuria are risk factors for ESRD, acute kidney injury and progressive CKD in both general and high-risk populations, independent of each other and of cardiovascular risk factors.
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            Acute kidney injury-epidemiology, outcomes and economics.

            Acute kidney injury (AKI) is a widespread problem of epidemic status. Compelling evidence indicates that the incidence of AKI is rapidly increasing, particularly among hospitalized patients with acute illness and those undergoing major surgery. This increase might be partially attributable to greater recognition of AKI, improved ascertainment in administrative data and greater sensitivity of consensus diagnostic and classification schemes. Other causes could be an ageing population, increasing incidences of cardiovascular disease, diabetes mellitus and chronic kidney disease (CKD), and an expanding characterization of modifiable risk factors, such as sepsis, administration of contrast media and exposure to nephrotoxins. The sequelae of AKI are severe and characterized by increased risk of short-term and long-term mortality, incident CKD and accelerated progression to end-stage renal disease. AKI-associated mortality is decreasing, but remains unacceptably high. Moreover, the absolute number of patients dying as a result of AKI is increasing as the incidence of the disorder increases, and few proven effective preventative or therapeutic interventions exist. Survivors of AKI, particularly those who remain on renal replacement therapy, often have reduced quality of life and consume substantially greater health-care resources than the general population as a result of longer hospitalizations, unplanned intensive care unit admissions and rehospitalizations.
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              Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease.

              To determine whether acute renal failure (ARF) increases the long-term risk of progressive chronic kidney disease (CKD), we studied the outcome of patients whose initial kidney function was normal or near normal but who had an episode of dialysis-requiring ARF and did not develop end-stage renal disease within 30 days following hospital discharge. The study encompassed 556,090 adult members of Kaiser Permanente of Northern California hospitalized over an 8 year period, who had pre-admission estimated glomerular filtration rates (eGFR) equivalent to or greater than 45 ml/min/1.73 m(2) and who survived hospitalization. After controlling for potential confounders such as baseline level of eGFR and diabetes status, dialysis-requiring ARF was independently associated with a 28-fold increase in the risk of developing stage 4 or 5 CKD and more than a twofold increased risk of death. Our study shows that in a large, community-based cohort of patients with pre-existing normal or near normal kidney function, an episode of dialysis-requiring ARF was a strong independent risk factor for a long-term risk of progressive CKD and mortality.
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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
                September 2014
                24 September 2014
                : 127
                : 1-4
                : 35-41
                Affiliations
                Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alta., Canada
                Author notes
                *Sean M. Bagshaw, Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Clinical Sciences Building, 2-124E, 8440-112 Street NW, Edmonton, AB T6G 2B7 (Canada), E-Mail bagshaw@ualberta.ca
                Article
                363671 Nephron Clin Pract 2014;127:35-41
                10.1159/000363671
                25343818
                © 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.

                Page count
                Figures: 1, Tables: 1, Pages: 7
                Categories
                Original Paper

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