IntroductionAcute 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.MethodsWe 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.ResultsModerate 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 <0.002), none of which achieved an AUC >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.ConclusionsTwo 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 registrationClinicalTrials.gov number NCT01209169.

Objectives: To determine which components of a residency Web site (RWS) are important to residency applicants. Methods: The authors performed a cross-sectional observational study of residency applicants. All applicants were invited to participate and were provided with a nine-question survey. Applicants were asked questions regarding the importance and impact of RWSs on the residency application process. They were also asked to rate items regarding content and aesthetics, and then rank all items in order of importance. Descriptive statistics are reported. Rank-order displays were determined using the Condorcet choice method. Results: One hundred eightyeight (82%) of the applicants responded to the survey. Seventy-eight percent of the respondents reported that information provided in an RWS influenced their decision to apply to a particular program (41% decided not to apply to at least one program based on the quality of its RWS). Applicants believed that presentation of the residency curriculum was most important. Information about the hospital and its affiliates, faculty and resident information, and research activities followed in the rank order. Least important to applicants were the aesthetic quality of the site, faculty/resident photographs, and educational resource materials. The authors report additional areas of content that applicants thought would be useful to view. Conclusions: The content, and not necessarily the aesthetic quality, of an RWS is important to residency applicants. The residency program Web site would seem to be an important factor in the applicant's decision to apply. The applicant's perspective provides training program directors and administrators with focused direction in Web site development or for upgrading existing RWSs for use by future applicants.

A biomarker panel of neutrophil gelatinase-associated lipocalin, interleukin-1ra, and Protein C was predictive of severe sepsis, septic shock, and death in ED patients with suspected sepsis. Further study is warranted to prospectively validate the clinical utility of these biomarkers and the sepsis score in risk-stratifying patients with suspected sepsis.