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      Oxidative Stress and ‘Monocyte Reprogramming’ in Septic Patients with Acute Kidney Injury Requiring CRRT

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          Abstract

          Oxidative stress (OS) and monocyte HLA-DR expression are known to be predictive of mortality in sepsis; nevertheless, limited information exists regarding sepsis with acute kidney injury (AKI). The aim of the study was to correlate these markers with outcome in septic patients with AKI requiring continuous renal replacement therapy (CRRT). Advanced oxidation protein products (AOPP) were measured in 32 patients on days 1, 3, 7, 14, 21, and 28. In 14 we assessed the percentage of monocytes expressing HLA-DR (%DR+) and the HLA-DR mean fluorescence intensity (MFI). 20 healthy volunteers, 17 septic patients without AKI and 20 septic AKI patients not treated by CRRT were used for comparison. The mortality rate was 59%. Septic CRRT patients had higher AOPP and lower %DR+ (p < 0.001, both) than healthy controls. They also had higher AOPP than septic patients who did not develop AKI (p < 0.001). No difference was found in AOPP, %DR+ and MFI between survivors and non-survivors (day 1 and subsequent measurements). No correlation was seen between severity scores and OS/HLA-DR. OS and HLA-DR expression are altered in septic patients with AKI undergoing CRRT. However, this study was not able to confirm the usefulness of these markers in predicting survival in this subset of patients.

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          Most cited references18

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          Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients*

          Acute renal failure is a complication in critically ill patients that has been associated with an excess risk of hospital mortality. Whether this reflects the severity of the disease or whether acute renal failure is an independent risk factor is unknown. The aim of this study was to analyze severity of illness and mortality in a group of critically ill patients with acute renal failure requiring renal replacement therapy in a number of Austrian intensive care units.
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            The outcome of acute renal failure in the intensive care unit according to RIFLE: model application, sensitivity, and predictability.

            The definition, classification, and choice of management of acute renal failure (ARF) in the setting of the intensive care unit (ICU) remain subjects of debate. To improve our approach to ARF in the ICU setting, we retrospectively applied the new classification of ARF put forward by the Acute Dialysis Quality Initiative group, RIFLE (acronym indicating Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal failure), to evaluate its sensitivity and specificity to predict renal and patient outcomes. RIFLE classification was applied to 183 patients with ARF admitted to the ICU (2002 to 2003) at the Northern General Hospital, Sheffield, UK. Patients were divided into 4 groups according to percentage of decrease in glomerular filtration rate from baseline. The risk group included 60 patients; injury group, 56 patients; failure group, 43 patients; and control group, 24 patients. Demographic, biochemical, hematologic, clinical, and long-term health status were studied and compared in the 4 groups. An attempt was made to evaluate, by means of logistic regression analysis and receiver operator characteristic curve analysis, the predictive value of RIFLE classification for mortality in the ICU. The failure group showed the worst parameters with regard to Acute Physiology and Chronic Health Evaluation (APACHE) II score, pH, lowest and highest mean arterial pressures, and Glasgow Coma Scale (P < 0.001). Mortality rate in the ICU (1 month) was significantly greater in the failure group compared with all groups (32 of 43 patients [74.4%]; P < 0.001) and, again, 6-month mortality rate (37 of 43 patients [86%]; P < 0.001). Receiver operator characteristic curve analysis showed that Simplified Acute Physiology Score (SAPS) II was more sensitive than APACHE II score for prediction of patient death in the risk and injury groups compared with the failure and control groups (risk group: SAPS II, 0.8 +/- 0.06; P < 0.001; APACHE II, 0.63 +/- 0.07; P = 0.14; injury group: SAPS II, 0.76 +/- 0.08; P < 0.001; APACHE II, 0.72 +/- 0.07; P = 0.006). RIFLE classification can improve the ability of such older and established ICU scoring systems as APACHE II and SAPS II in predicting outcome of ICU patients with ARF.
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              Possible role of increased oxidant stress in multiple organ failure after systemic inflammatory response syndrome.

              Host response to infection and other forms of tissue injury have been termed systemic inflammatory response syndrome (SIRS). This inflammatory response can frequently be accompanied by oxidative injury in one or more organ systems in the body. The objective of this report was to clarify the possible role of oxidative stress in the development of multiple organ failure (MOF) in patients with SIRS. Prospective clinical study. Intensive care unit in a university hospital. A total of 214 consecutive patients (mean age, 57.1 +/- 17.4 yrs; range, 13 to 84 yrs; 148 men and 66 women). At the time of admission, 139 patients fulfilled the clinical criteria for SIRS. None. We measured plasma concentrations of thiobarbituric acid reactant substances (TBARS), as an index of oxidative stress, every day from the point of admission to the intensive care unit until discharge or death. Furthermore, all variables of the SIRS score and the Sequential Organ Failure Assessment score were collected every day. At the time of admission, plasma TBARS concentrations in SIRS patients with MOF were significantly higher than those in SIRS patients without MOF (2.3 +/- 0.9 vs. 1.9 +/- 0.6 nmol/mL, p <.01), and there was a significant correlation between plasma TBARS concentration and Sequential Organ Failure Assessment score (r2 =.18, p <.001). Furthermore, the duration of SIRS persistence was significantly associated with the percentage increase in plasma TBARS concentration during SIRS persistence in those patients in whom the duration of SIRS was confirmed (r2 =.73, p <.001). The duration of SIRS was significantly higher in patients who developed MOF than in patients who did not develop MOF (6.9 vs. 3.2 days, p <.001). The percentage increase in plasma TBARS concentration during SIRS was also significantly higher in patients who developed MOF than in patients who did not develop MOF (57.1% vs. 15.8%, p <.001). It can be concluded that processes of oxidative stress in connection with continued SIRS may promote the development of MOF.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2008
                March 2008
                15 February 2008
                : 26
                : 2
                : 188-192
                Affiliations
                Departments of aNephrology, Dialysis and Transplant and bIntensive Care, St. Bortolo Hospital, Vicenza, Italy
                Article
                117308 Blood Purif 2008;26:188–192
                10.1159/000117308
                18277069
                be24e2c5-13bc-4cfd-ae91-99a9e4ba2741
                © 2008 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
                : 04 July 2007
                : 20 October 2007
                Page count
                Figures: 2, Tables: 2, References: 26, Pages: 5
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Sepsis outcome,Acute kidney injury,Advanced oxidation protein products,Monocyte HLA-DR expression

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