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      Acute kidney injury: from clinical to molecular diagnosis

      editorial
      Critical Care
      BioMed Central

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          Abstract

          The RIFLE classification was introduced in 2004 to describe the presence of acute kidney injury (AKI) and to define its clinical stage, based upon the serum creatinine level and urine output. The same criteria, although slightly modified, are used in the other scoring systems AKIN and KDIGO. Mortality and morbidity remain high in AKI, suggesting that current diagnostic methods are suboptimal, poorly accurate, and often timely inadequate in detecting the presence of early kidney injury. Conversely, a growing body of evidence indicates that new AKI biomarkers can be used to both rule out AKI and to assess high-risk conditions or the presence of subclinical forms. Neutrophil gelatinase-associated lipocalin or cell cycle arrest biomarkers seem to be sensitive and specific enough to be used in conjunction with existing markers of AKI for better classifying renal injury as well as dysfunction. Improvements in diagnosis, risk identification, stratification, prognosis, and therapeutic monitoring may improve prevention and protection from organ damage and help to identify patients at risk, allowing individualized therapy. In this view, we may say that AKI diagnosis has finally moved from clinical to molecular level with potential benefits for the patients because similar progress has been shown in other disciplines.

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          Subclinical AKI--an emerging syndrome with important consequences.

          According to guidelines published by Kidney Disease: Improving Global Outcomes, patients at risk of acute kidney injury (AKI) should be managed according to their susceptibilities and exposures. Clinical evaluation of a patient's risk of acute loss of renal function is of undisputed importance. However, such evaluations can be hindered by the complex presentations of critically ill patients and the lack of methods to detect early kidney damage. In this regard, a tool for diagnosis and stratification of patients at risk of AKI would complement clinical assessments and enable improved therapeutic decision-making. Emerging evidence suggests that 15-20% of patients who do not fulfil current serum-creatinine-based consensus criteria for AKI are nevertheless likely to have acute tubular damage, which is associated with adverse outcomes. This evidence supports reassessment of the concept and evolution of the definition of AKI to incorporate biomarkers of tubular damage.
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            Subclinical AKI is still AKI

            The concept of acute kidney syndromes has shifted in recent years from acute renal failure to acute kidney injury (AKI). AKI implies injury or damage but not necessarily dysfunction. The human kidney has an important glomerular function reserve, and dysfunction becomes evident only when more than 50% of the renal mass is compromised. Recent AKI classifications include even slight changes in serum creatinine, acknowledging that this condition is associated with worse outcomes. This, however, still represents a functional criterion for AKI and implies a glomerular filtration rate alteration that may be a late phenomenon in the time course of the syndrome. An early diagnosis of AKI by using tubular damage biomarkers preceding filtration function loss is possible today. Some studies have shown evidence that there is an additional value of new biomarkers not only because they allow a diagnosis to be made earlier but also because they allow a kidney injury to be diagnosed even in the absence of subsequent dysfunction. Only recently, tubular damage without glomerular function loss was demonstrated to be associated with worse renal and overall outcomes. For this condition, the term 'subclinical' AKI has been introduced, challenging the traditional view that a kidney problem is clinically relevant, only when a loss of filtration function becomes apparent. A new domain of AKI diagnosis could then include functional criteria and damage criteria. This may have an impact on the epidemiology, prevention, and management of AKI.
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              Neutrophil Gelatinase-Associated Lipocalin: Ready for Routine Clinical Use? An International Perspective

              Acute kidney injury (AKI) remains a challenge in terms of diagnosis and classification, its morbidity and mortality remaining high in the face of improving clinical protocols. Current clinical criteria use serum creatinine (sCr) and urine output to classify patients. Ongoing research has identified novel biomarkers that may improve the speed and accuracy of patient evaluation and prognostication, yet the route from basic science to clinical practice remains poorly paved. International evidence supporting the use of plasma neutrophil gelatinase-associated lipocalin (NGAL) as a valuable biomarker of AKI and chronic kidney disease (CKD) for a number of clinical scenarios was presented at the 31st International Vicenza Course on Critical Care Nephrology, and these data are detailed in this review. NGAL was shown to be highly useful alongside sCr, urinary output, and other biomarkers in assessing kidney injury; in patient stratification and continuous renal replacement therapy (CRRT) selection in paediatric AKI; in assessing kidney injury in conjunction with sCr in sepsis; in guiding resuscitation protocols in conjunction with brain natriuretic peptide in burn patients; as an early biomarker of delayed graft function and calcineurin inhibitor nephrotoxicity in kidney transplantation from extended criteria donors; as a biomarker of cardiovascular disease and heart failure, and in guiding CRRT selection in the intensive care unit and emergency department. While some applications require further clarification by way of larger randomised controlled trials, NGAL nevertheless demonstrates promise as an independent biological marker with the potential to improve earlier diagnosis and better assessment of risk groups in AKI and CKD. This is a critical element in formulating quick and accurate decisions for individual patients, both in acute scenarios and in long-term care, in order to improve patient prognostics and outcomes.
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                Author and article information

                Contributors
                +39-444-753869 , +39-444-753949 , cronco@goldnet.it
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                7 July 2016
                7 July 2016
                2016
                : 20
                : 201
                Affiliations
                Department of Nephrology Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, Viale Rodolfi 37, Vicenza, 36100 Italy
                Article
                1373
                10.1186/s13054-016-1373-7
                4936182
                27384344
                22be37d1-cb5c-4931-90f7-d9f5bd1e56a8
                © The Author(s). 2016

                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. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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                Emergency medicine & Trauma
                Emergency medicine & Trauma

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