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      Current Use of Biomarkers in Acute Kidney Injury: Report and Summary of Recommendations from the 10 th Acute Dialysis Quality Initiative Consensus Conference

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          Abstract

          Over the last decade there has been considerable progress in the discovery and development of biomarkers of kidney disease, and several have now been evaluated in different clinical settings. While there is a growing literature on the performance of various biomarkers in clinical studies, there is limited information on how these biomarkers would be utilized by clinicians to manage patients with acute kidney injury (AKI). Recognizing this gap in knowledge, we convened the 10th Acute Dialysis Quality Initiative (ADQI) meeting to review the literature on biomarkers in AKI and their application in clinical practice. We asked an international group of experts to assess four broad areas for biomarker utilization for AKI: risk assessment, diagnosis and staging; differential diagnosis; prognosis and management and novel physiological techniques including imaging. This article provides a summary of the key findings and recommendations of the group, to equip clinicians to effectively use biomarkers in AKI.

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

          Kianoush B Kashani, Ali Al-Khafaji, Thomas Ardiles … (2013)
          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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            Universal definition of myocardial infarction.

            Kristian Thygesen, Joseph Alpert, Harvey White (2007)
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              Acute Kidney Injury and Mortality in Hospitalized Patients

              Henry Wang, Paul Muntner, Glenn Chertow … (2012)
              Background: The objective of this study was to determine the incidence of acute kidney injury (AKI) and its relation with mortality among hospitalized patients. Methods: Analysis of hospital discharge and laboratory data from an urban academic medical center over a 1-year period. We included hospitalized adult patients receiving two or more serum creatinine (sCr) measurements. We excluded prisoners, psychiatry, labor and delivery, and transferred patients, ‘bedded outpatients’ as well as individuals with a history of kidney transplant or chronic dialysis. We defined AKI as (a) an increase in sCr of ≥0.3 mg/dl; (b) an increase in sCr to ≥150% of baseline, or (c) the initiation of dialysis in a patient with no known history of prior dialysis. We identified factors associated with AKI as well as the relationships between AKI and in-hospital mortality. Results: Among the 19,249 hospitalizations included in the analysis, the incidence of AKI was 22.7%. Older persons, Blacks, and patients with reduced baseline kidney function were more likely to develop AKI (all p < 0.001). Among AKI cases, the most common primary admitting diagnosis groups were circulatory diseases (25.4%) and infection (16.4%). After adjustment for age, sex, race, admitting sCr concentration, and the severity of illness index, AKI was independently associated with in-hospital mortality (adjusted odds ratio 4.43, 95% confidence interval 3.68–5.35). Conclusions: AKI occurred in over 1 of 5 hospitalizations and was associated with a more than fourfold increased likelihood of death. These observations highlight the importance of AKI recognition as well as the association of AKI with mortality in hospitalized patients.
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 0323470
                Journal ID (pubmed-jr-id): 5428
                Journal ID (nlm-ta): Kidney Int
                Journal ID (iso-abbrev): Kidney Int.
                Title: Kidney international
                ISSN (Print): 0085-2538
                ISSN (Electronic): 1523-1755
                Publication date Nihms-submitted: 2 November 2013
                Publication date (Electronic): 09 October 2013
                Publication date (Print): March 2014
                Publication date PMC-release: 16 October 2014
                Volume: 85
                Issue: 3
                Pages: 513-521
                Affiliations
                [1 ] School of Medicine & Medical Science, University College Dublin, Dublin, Ireland
                [2 ] Department of Medicine, University of California San Diego, San Diego, CA, USA
                [3 ] Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA
                [4 ] Renal Division, St. Bortolo Hospital, International Renal Research Institute, Vicenza, Italy
                [5 ] Department of Nephrology, Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia
                [6 ] Christchurch Kidney Research Group, Department of Medicine, University of Otago, Christchurch, New Zealand
                [7 ] Department of Critical Care Medicine, School of Medicine, Pittsburgh, USA
                [8 ] Department of Anesthesiology and Critical Care Medicine, George Washington University Medical Center, Washington, DC, USA
                [9 ] Department of Nephrology Dialysis & Transplantation, San Bortolo Hospital, Vicenza, Italy
                [10 ] International Renal Research Institute (IRRIV), Vicenza, Italy
                [11 ] Department of Intensive Care Adults, Erasmus MC University Medical Centre Rotterdam, Rotterdam, The Netherlands
                [12 ] Division of Nephrology and Center for Immunity, inflammation and Regenerative Medicine, University of Virginia, Charlottesville, VA
                Author notes
                [*]

                Denotes co-first authors

                Correspondence: Ravindra L Mehta MD, FACP, FASN, FRCP UCSD Medical Centre 8342, 200 W Arbor Drive, San Diego, CA 92103 Tel 619-543-7310; Fax 619-543-7420 rmehta@ 123456ucsd.edu
                Article
                Manuscript ID: NIHMS519731
                DOI: 10.1038/ki.2013.374
                PMC ID: 4198530
                PubMed ID: 24107851
                SO-VID: f09d16d3-51d2-4e67-8ed3-89a4ceef0c11
                History
                Categories
                Subject: Article

                ScienceOpen disciplines: Nephrology
                Keywords: acute kidney injury,acute renal failure,biomarkers,diagnosis,prognosis,surveillance,monitoring,staging,differential diagnosis,management
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: acute kidney injury, acute renal failure, biomarkers, diagnosis, prognosis, surveillance, monitoring, staging, differential diagnosis, management

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