We conducted a two-stage program in which we first collected blood and urine samples from three distinct cohorts (Discovery study) to identify novel protein biomarkers for AKI. These single-center studies were used to identify the best biomarkers among 340 proteins, including novel candidates and previously described biomarkers such as kidney injury marker-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), cystatin-C, interleukin-18 (IL-18), pi-glutathione S-transferase (pi-GST), and liver fatty acid-binding protein (L-FABP). Data from all three cohorts were pooled for analysis. A fourth cohort (Sapphire study) was assembled from 35 clinical sites in North America and Europe and used to validate the performance of the best biomarkers (urine tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7)) from the Discovery study (Figure 1). The Sapphire study was approved by the Western Institutional Review Board (Olympia, Washington, USA). In addition, the study protocols were approved by investigational review boards/ethics committees as required, by each participating institution. All subjects (or authorized representatives) provided written informed consent. The Sapphire study was designed and reported according to the STROBE guidelines [9 (link)]. As shown in Figure 1, the Discovery study enrolled patients who were admitted to an intensive care unit (any type), were at least 18 years of age and typically had at least one recognized risk factor for AKI. The Sapphire (validation) study enrolled critically ill patients who were at least 21 years of age, admitted to the intensive care unit within 24 hours of enrollment, expected to remain in the ICU with a urinary catheter for at least 48 hours and were critically ill (respiratory or cardiovascular dysfunction). Patients with known existing moderate or severe AKI (KDIGO [6 ] stage 2 or 3) were excluded. Sample size for the Sapphire study was based on the results of the Discovery study and is explained in detail in Additional file 1.
Kashani K., Al-Khafaji A., Ardiles T., Artigas A., Bagshaw S.M., Bell M., Bihorac A., Birkhahn R., Cely C.M., Chawla L.S., Davison D.L., Feldkamp T., Forni L.G., Gong M.N., Gunnerson K.J., Haase M., Hackett J., Honore P.M., Hoste E.A., Joannes-Boyau O., Joannidis M., Kim P., Koyner J.L., Laskowitz D.T., Lissauer M.E., Marx G., McCullough P.A., Mullaney S., Ostermann M., Rimmelé T., Shapiro N.I., Shaw A.D., Shi J., Sprague A.M., Vincent J.L., Vinsonneau C., Wagner L., Walker M.G., Wilkerson R.G., Zacharowski K, & Kellum J.A. (2013). Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Critical Care, 17(1), R25.
Publication 2013
BiomarkersBlood Cardiovascular Critically ill Cystatin cEthics committees Glutathione s transferase Injury Institutional review board Insulin like growth factor binding protein 7 Interleukin 18Kidney Liver fatty acid binding protein Neutrophil gelatinase associated lipocalin OlympiaPatientsProteins RespiratorySapphire Timp 2 Tissue inhibitor of metalloproteinases 2Urinary catheterUrine
Corresponding Organization : University of Pittsburgh
Other organizations :
Mayo Clinic, Theodore Roosevelt High School, Valleywise Health, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Universitat Autònoma de Barcelona, University of Alberta, Karolinska University Hospital, University of Florida, NewYork–Presbyterian Brooklyn Methodist Hospital, Bruce W. Carter VA Medical Center, Washington University Medical Center, George Washington University, University of Duisburg-Essen, Albert Einstein College of Medicine, Montefiore Medical Center, Virginia Commonwealth University Medical Center, Otto-von-Guericke University Magdeburg, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Ghent University Hospital, Université de Bordeaux, Innsbruck Medical University, Hospital of the University of Pennsylvania, University of Chicago, Duke University Hospital, Duke Medical Center, University of Maryland, Baltimore, Universitätsklinikum Aachen, Providence Hospital, Ascension, University of California, San Diego, St Thomas' Hospital, King's College London, Hospices Civils de Lyon, Beth Israel Deaconess Medical Center, Walker (United States), Joseph M. Still Research Foundation, Erasmus Hospital, Melun Hospital, Medical University of Vienna, Tampa General Hospital, Goethe University Frankfurt, University Hospital Frankfurt
Protein biomarkers (including kidney injury marker-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), cystatin-C, interleukin-18 (IL-18), pi-glutathione S-transferase (pi-GST), and liver fatty acid-binding protein (L-FABP))
dependent variables
Acute kidney injury (AKI)
control variables
Age (at least 18 years for Discovery study, at least 21 years for Sapphire study)
Admission to intensive care unit (any type for Discovery study, within 24 hours of enrollment for Sapphire study)
Presence of at least one recognized risk factor for AKI (Discovery study)
Expected to remain in the ICU with a urinary catheter for at least 48 hours (Sapphire study)
Critically ill (respiratory or cardiovascular dysfunction) (Sapphire study)
Absence of known existing moderate or severe AKI (KDIGO stage 2 or 3) (Sapphire study)
positive controls
Not explicitly mentioned
negative controls
Not explicitly mentioned
Annotations
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