BACKGROUND: Acute kidney injury (AKI) is associated with poor outcome in critically ill children. While data extracted from retrospective study of pediatric populations demonstrate a high incidence of AKI, the literature lacks focused and comprehensive multicenter studies describing AKI risk factors, epidemiology, and outcome. Additionally, very few pediatric studies have examined novel urinary biomarkers outside of the cardiopulmonary bypass population. METHODS/DESIGN: This is a prospective observational study. We anticipate collecting data on over 5000 critically ill children admitted to 31 pediatric intensive care units (PICUs) across the world during the calendar year of 2014. Data will be collected for seven days on all children older than 90 days and younger than 25 years without baseline stage 5 chronic kidney disease, chronic renal replacement therapy, and outside of 90 days of a kidney transplant or from surgical correction of congenital heart disease. Data to be collected includes demographic information, admission diagnoses and co-morbidities, and details on fluid and vasoactive resuscitation used. The renal angina index will be calculated integrating risk factors and early changes in serum creatinine and fluid overload. On days 2-7, all hemodynamic and pertinent laboratory values will be captured focusing on AKI pertinent values. Daily calculated values will include % fluid overload, fluid corrected creatinine, and KDIGO AKI stage. Urine will be captured twice daily for biomarker analysis on Days 0-3 of admission. Biomarkers to be measured include neutrophil gelatinase lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (l-FABP), and interleukin-18 (IL-18). The primary outcome to be quantified is incidence rate of severe AKI on Day 3 (Day 3-AKI). Prediction of Day 3-AKI by the RAI and after incorporation of biomarkers with RAI will be analyzed. DISCUSSION: The Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology (AWARE) study, creates the first prospective international pediatric all cause AKI data warehouse and biologic sample repository, providing a broad and invaluable resource for critical care nephrologists seeking to study risk factors, prediction, identification, and treatment options for a disease syndrome with high associated morbidity affecting a significant proportion of hospitalized children. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01987921.

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Background: Acute kidney injury occurs in one in four children admitted to an intensive care unit (ICU) and its severity is independently associated with increased patient morbidity and mortality. Early prediction of acute kidney injury has the potential to improve outcomes. In smaller, single-centre trial populations, we have previously derived and validated the performance of a renal angina index, a context-driven risk stratification system, to predict severe acute kidney injury in children and adolescents. Here, we tested the predictive accuracy of this index for severe acute kidney injury in a large heterogeneous population. Methods: We did a prospective, observational study (AWARE) that recruited patients in the ICUs of 32 hospitals in nine countries across Asia, Australia, Europe, and North America. All patients aged between 3 months and 25 years who were admitted to an ICU at least 48 h previously were eligible. Exclusion criteria were a history of stage 5 chronic kidney disease (ie, estimated glomerular filtration rate <15 mL/min per 1·73m 2 or on maintenance dialysis) or kidney transplantation in the preceding 90 days. Patients' medical records were reviewed to collect data up to 3 months before (serum creatinine only), daily during the first 7 days, and on day 28 after ICU admission. For the assessment of the renal angina index, we included patients from the AWARE study who had full data from the day of ICU admission, day 3, and day 28, including serum creatinine concentrations and urine output measurements. The primary outcome was the presence of severe acute kidney injury (stage 2–3 acute kidney injury, according to Kidney Disease Improving Global Outcomes [KDIGO] guidelines) on the third day after ICU admission. We compared the performance of the renal angina index with changes in serum creatinine relative to baseline for prediction of the primary outcome. A score of eight points or more on the renal angina index defined fulfilment of renal angina; serum creatinine concentration relative to baseline was calculated using maximum serum creatinine concentration in the first 12 h of ICU admission). This trial is registered with ClinicalTrials.gov, number NCT01987921. Findings: Between Jan 1 and Dec 31, 2014, we obtained data for 1590 patients. 286 patients (18%) had fulfilment of renal angina. At day 3, severe acute kidney injury occurred in 121 (42%) patients positive for renal angina and 247 (19%) patients negative for renal angina (relative risk [RR] 2·23, 95% CI 1·87–2.66, p<0·0001). Of 368 (23%) patients with severe acute kidney injury, more had increased use of renal replacement and increased mortality than of the 1222 (77%) patients without severe acute kidney injury (40 [11%] vs 18 [2%], p<0.0001; and 28 [8%] vs 53 [4%], p=0·01). Fulfilment of renal angina showed better prediction for severe acute kidney injury than serum creatinine greater than baseline (RR 1.61, 95% CI 1·33–1·93; p<0·0001), which was maintained on multivariate regression (independent odds ratio for fulfilment of renal angina 3·21, 95% CI 2·20–4·67 vs serum creatinine greater than baseline 0·68, 0·49–4·94). Interpretation: Earlier and better prediction of severe acute kidney injury has the potential to improve patient outcomes associated with acute kidney injury. Compared with isolated, context-free changes in serum creatinine, renal angina risk assessment improved accuracy for prediction of severe acute kidney injury in critically ill children and young people. Funding: US National Institutes of Health.

Background: The prevalence of continuous renal replacement therapy (CRRT) utilization in critically ill patients with acute kidney is increasing. In comparison to published and on-going trials attempting to answer questions surrounding the optimal timing of CRRT initiation, anticoagulation, and modality, a paucity of literature describes the quality of the therapy delivered. Methods: We conducted a single-center process improvement project to determine if a methodology to assess the quality of CRRT delivery could lead to improvement in CRRT delivery outcomes. We developed three broad categories of objective CRRT metrics to assess longitudinally, enabling creation of a CRRT Dashboard. Following the objective categories of "filter", "prescription", and "fluid balance" over time allowed us to perform quarterly analyses, target provider based CRRT education, and address variation from our standard of care. From 2012 to 2017, 184 critically ill patients received CRRT. Results: We report a mean filter life of 56 + 28.4 h, a 60-h filter life of 62%, and unplanned filter changes of 15%. Compared to a minimum target prescription of 2000 ml/1.73 m2/hour, we report the mean prescribed dose (2300 ml/1.73 m2/hour) and the rate of patients receiving at least the minimum prescription (98%). Finally, using a 10% deviation in the acceptable range of desired daily patient fluid balance, we report 83% CRRT patient days achieving an acceptable stipulated fluid goal. Conclusion: We report the implementation of a quality dashboard and adopting quality improvement strategies provided a platform for measuring adherence to our institutional standards and the delivery of CRRT, specifically on the process of the care.