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      Acute kidney injury in the ICU: from injury to recovery: reports from the 5th Paris International Conference

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      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ,
      Annals of Intensive Care
      Springer Paris
      Acute renal failure, Epidemiology, Renal replacement, Therapy, Anticoagulation, Renal blood flow, Extracorporeal epuration, Biomarkers

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          Abstract

          The French Intensive Care Society organized its yearly Paris International Conference in intensive care on June 18–19, 2015. The main purpose of this meeting is to gather the best experts in the field in order to provide the highest quality update on a chosen topic. In 2015, the selected theme was: “Acute Renal Failure in the ICU: from injury to recovery.” The conference program covered multiple aspects of renal failure, including epidemiology, diagnosis, treatment and kidney support system, prognosis and recovery together with acute renal failure in specific settings. The present report provides a summary of every presentation including the key message and references and is structured in eight sections: (a) diagnosis and evaluation, (b) old and new diagnosis tools, (c) old and new treatments, (d) renal replacement therapy and management, (e) acute renal failure witness of other conditions, (f) prognosis and recovery, (g) extracorporeal epuration beyond the kidney, (h) the use of biomarkers in clinical practice http://www.srlf.org/5th-paris-international-conference-jeudi-18-et-vendredi-19-juin-2015/.

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          Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

          Introduction Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P 0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. Trial registration ClinicalTrials.gov number NCT01209169.
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            Acute kidney injury increases risk of ESRD among elderly.

            Risk for ESRD among elderly patients with acute kidney injury (AKI) has not been studied in a large, representative sample. This study aimed to determine incidence rates and hazard ratios for developing ESRD in elderly individuals, with and without chronic kidney disease (CKD), who had AKI. In the 2000 5% random sample of Medicare beneficiaries, clinical conditions were identified using Medicare claims; ESRD treatment information was obtained from ESRD registration during 2 yr of follow-up. Our cohort of 233,803 patients were hospitalized in 2000, were aged > or = 67 yr on discharge, did not have previous ESRD or AKI, and were Medicare-entitled for > or = 2 yr before discharge. In this cohort, 3.1% survived to discharge with a diagnosis of AKI, and 5.3 per 1000 developed ESRD. Among patients who received treatment for ESRD, 25.2% had a previous history of AKI. After adjustment for age, gender, race, diabetes, and hypertension, the hazard ratio for developing ESRD was 41.2 (95% confidence interval [CI] 34.6 to 49.1) for patients with AKI and CKD relative to those without kidney disease, 13.0 (95% CI 10.6 to 16.0) for patients with AKI and without previous CKD, and 8.4 (95% CI 7.4 to 9.6) for patients with CKD and without AKI. In summary, elderly individuals with AKI, particularly those with previously diagnosed CKD, are at significantly increased risk for ESRD, suggesting that episodes of AKI may accelerate progression of renal disease.
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              Acute kidney injury and chronic kidney disease: an integrated clinical syndrome.

              The previous conventional wisdom that survivors of acute kidney injury (AKI) tend to do well and fully recover renal function appears to be flawed. AKI can cause end-stage renal disease (ESRD) directly, and increase the risk of developing incident chronic kidney disease (CKD) and worsening of underlying CKD. In addition, severity, duration, and frequency of AKI appear to be important predictors of poor patient outcomes. CKD is an important risk factor for the development and ascertainment of AKI. Experimental data support the clinical observations and the bidirectional nature of the relationships between AKI and CKD. Reductions in renal mass and nephron number, vascular insufficiency, cell cycle disruption, and maladaptive repair mechanisms appear to be important modulators of progression in patients with and without coexistent CKD. Distinction between AKI and CKD may be artificial. Consideration should be given to the integrated clinical syndrome of diminished GFR, with acute and chronic stages, where spectrum of disease state and outcome is determined by host factors, including the balance of adaptive and maladaptive repair mechanisms over time. Physicians must provide long-term follow-up to patients with first episodes of AKI, even if they presented with normal renal function.
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                Author and article information

                Contributors
                rinaldo.bellomo@austin.org.au
                cronco@goldnet.it
                rmehta@ucsd.edu
                piasfar@chu-angers.fr
                julie.helms@chru-strasbourg.fr
                michael.darmon@chu-st-etienne.fr
                jean-luc.diehl@aphp.fr
                jacques.duranteau@aphp.fr
                Eric.Hoste@UGent.be
                olivier.joannes-boyau@chu-bordeaux.fr
                matthieu.m.legrand@gmail.com
                nicolas.lerolle@univ-angers.fr
                manu.malbrain@skynet.be
                johan.martensson@austin.org.au
                hmoudemans@gmail.com
                parienti-jj@chu-caen.fr
                dpayen1234@orange.fr
                sophie.perinel.ragey@univ-st-etienne.fr
                esther.peters@radboudumc.nl
                peter.pickkers@radboudumc.nl
                eric.rondeau@aphp.fr
                marie.schetz@uzleuven.be
                cvinsonneau@ch-bethune.fr
                julia.wendon@kcl.ac.uk
                zhanglinglzy@163.com
                pierre-francois.laterre@uclouvain.be
                Journal
                Ann Intensive Care
                Ann Intensive Care
                Annals of Intensive Care
                Springer Paris (Paris )
                2110-5820
                4 May 2017
                4 May 2017
                2017
                : 7
                : 49
                Affiliations
                [1 ]ISNI 0000 0004 1936 7857, GRID grid.1002.3, Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Department of Epidemiology and Preventive Medicine, , Monash University, ; Melbourne, VIC Australia
                [2 ]GRID grid.410678.c, Department of ICU, , Austin Health, ; Heidelberg, Australia
                [3 ]Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV), Vicenza, Italy
                [4 ]ISNI 0000 0001 2107 4242, GRID grid.266100.3, Vice Chair Clinical Research, Department of Medicine, , University of California San Diego, ; La Jolla, CA USA
                [5 ]ISNI 0000 0004 0472 0283, GRID grid.411147.6, Département de Réanimation Médicale et de Médecine Hyperbare, , Centre Hospitalier Universitaire, ; Angers, France
                [6 ]ISNI 0000 0001 2248 3363, GRID grid.7252.2, Laboratoire de Biologie Neurovasculaire et Mitochondriale Intégrée, CNRS UMR 6214 - INSERM U1083, , Université Angers, PRES L’UNAM, ; Angers, France
                [7 ]ISNI 0000 0001 2177 138X, GRID grid.412220.7, Service de Réanimation Médicale, Nouvel Hôpital Civil, , Hôpitaux Universitaires de Strasbourg, ; Strasbourg, France
                [8 ]ISNI 0000 0001 2157 9291, GRID grid.11843.3f, EA 7293, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Faculté de médecine, , Université de Strasbourg, ; Strasbourg, France
                [9 ]ISNI 0000 0001 2158 1682, GRID grid.6279.a, Medical-Surgical ICU, , Saint-Etienne University Hospital and Jean Monnet University, ; Saint-Étienne, France
                [10 ]GRID grid.414093.b, Medical ICU, AP-HP, , Georges Pompidou European Hospital, ; Paris, France
                [11 ]ISNI 0000 0001 2188 0914, GRID grid.10992.33, INSERM UMR_S1140, , Paris Descartes University and Sorbonne Paris Cité, ; Paris, France
                [12 ]ISNI 0000 0001 2181 7253, GRID grid.413784.d, AP-HP, Service d’Anesthésie-Réanimation, Hôpitaux Universitaires Paris-Sud, , Université Paris-Sud, Hôpital de Bicêtre, ; Le Kremlin-Bicêtre, France
                [13 ]ISNI 0000 0001 2069 7798, GRID grid.5342.0, ICU, Ghent University Hospital, , Ghent University, ; Ghent, Belgium
                [14 ]ISNI 0000 0000 8597 7208, GRID grid.434261.6, , Research Foundation-Flanders (FWO), ; Brussels, Belgium
                [15 ]ISNI 0000 0004 0593 7118, GRID grid.42399.35, ICU, , University Hospital of Bordeaux, ; Bordeaux, France
                [16 ]Department of Anesthesiology and Critical Care and Burn Unit, Hôpitaux Universitaire St-Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris (AP-HP), University of Paris, Paris, France
                [17 ]ISNI 0000 0004 0472 0283, GRID grid.411147.6, Département de Réanimation Médicale et de Médecine Hyperbare, , CHU, ; Angers, France
                [18 ]Ziekenhuis Netwerk Antwerpen, ZNA, Stuivenberg, Belgium
                [19 ]ISNI 0000 0001 0162 7225, GRID grid.414094.c, Department of Intensive Care, , Austin Hospital, ; Melbourne, VIC Australia
                [20 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Section of Anaesthesia and Intensive Care Medicine, Department of Physiology and Pharmacology, , Karolinska Institutet, ; Stockholm, Sweden
                [21 ]ISNI 0000 0004 0435 165X, GRID grid.16872.3a, Department of Intensive Care, , VU Medical Centre, ; Amsterdam, The Netherlands
                [22 ]ISNI 0000 0004 0472 0160, GRID grid.411149.8, Department of Infectious Diseases, , University Hospital, ; Caen, France
                [23 ]ISNI 0000 0004 0472 0160, GRID grid.411149.8, Department of Biostatistic and Clinical Research, , University Hospital, ; Caen, France
                [24 ]ISNI 0000 0000 9725 279X, GRID grid.411296.9, Department of Anesthesia and Critical Care, SAMU, , Lariboisière University Hospital, ; Paris, France
                [25 ]ISNI 0000 0001 2158 1682, GRID grid.6279.a, Medical-Surgical ICU, Saint-Etienne University Hospital, , Jean Monnet University Saint-Etienne, ; Saint-Étienne, France
                [26 ]ISNI 0000 0004 0444 9382, GRID grid.10417.33, Department of Pharmacology and Toxicology, , Radboud university Medical Center, ; Nijmegen, The Netherlands
                [27 ]ISNI 0000 0004 0444 9382, GRID grid.10417.33, Department of Intensive Care Medicine, , Radboud University Medical Center, ; Nijmegen, The Netherlands
                [28 ]ISNI 0000 0001 1955 3500, GRID grid.5805.8, Urgences néphrologiques et Transplantation rénale, Hôpital Tenon, , Université Paris 6, ; Paris, France
                [29 ]ISNI 0000 0001 0668 7884, GRID grid.5596.f, Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, , KU Leuven, ; Louvain, Belgium
                [30 ]GRID grid.440373.7, Service de Réanimation et Surveillance continue, , Centre Hospitalier de BETHUNE, ; Bethune, France
                [31 ]ISNI 0000 0004 0391 9020, GRID grid.46699.34, , Kings College Hospital Foundation Trust, ; London, UK
                [32 ]ISNI 0000 0004 1770 1022, GRID grid.412901.f, Department of Nephrology, , West China Hospital of Sichuan University, ; Sichuan, Chengdu, China
                [33 ]ISNI 0000 0001 2294 713X, GRID grid.7942.8, Intensive Care Unit, Saint Luc University Hospital, , UCL, ; Louvain, Belgium
                Article
                260
                10.1186/s13613-017-0260-y
                5418176
                28474317
                e3133578-62be-4e0b-b672-f74d96989c3d
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 9 June 2016
                : 15 March 2017
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                Emergency medicine & Trauma
                acute renal failure,epidemiology,renal replacement,therapy,anticoagulation,renal blood flow,extracorporeal epuration,biomarkers

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