Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication.

RationaleWe recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest.ObjectivesWe now validate a clinical test for urinary [TIMP-2]·[IGFBP7] at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients.MethodsWe conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2]·[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test.Measurements and main resultsUrinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2]·[IGFBP7] test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary [TIMP-2]·[IGFBP7] greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2]·[IGFBP7] remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP-2]·[IGFBP7]).ConclusionsUrinary [TIMP-2]·[IGFBP7] greater than 0.3 (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962)

The Medical-Legal Aspects of Acute Care Medicine: A Resource for Clinicians, Administrators, and Risk Managers

The Medical-Legal Aspects of Acute Care Medicine: A Resource for Clinicians, Administrators, and Risk Managers is a comprehensive resource intended to provide a state-of-the-art overview of complex ethical, regulatory, and legal issues of importance to clinical healthcare professionals in the area of acute care medicine; including, for example, physicians, advanced practice providers, nurses, pharmacists, social workers, and care managers. In addition, this book also covers key legal and regulatory issues relevant to non-clinicians, such as hospital and practice administrators; department heads, educators, and risk managers. This text reviews traditional and emerging areas of ethical and legal controversies in healthcare such as resuscitation; mass-casualty event response and triage; patient autonomy and shared decision-making; medical research and teaching; ethical and legal issues in the care of the mental health patient; and, medical record documentation and confidentiality. Furthermore, this volume includes chapters dedicated to critically important topics, such as team leadership, the team model of clinical care, drug and device regulation, professional negligence, clinical education, the law of corporations, tele-medicine and e-health, medical errors and the culture of safety, regulatory compliance, the regulation of clinical laboratories, the law of insurance, and a practical overview of claims management and billing