The epidemiologic characteristics of children and young adults with acute kidney injury have been described in single-center and retrospective studies. We conducted a multinational, prospective study involving patients admitted to pediatric intensive care units to define the incremental risk of death and complications associated with severe acute kidney injury. We used the Kidney Disease: Improving Global Outcomes criteria to define acute kidney injury. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury (plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours) and was assessed for the first 7 days of intensive care. All patients 3 months to 25 years of age who were admitted to 1 of 32 participating units were screened during 3 consecutive months. The primary outcome was 28-day mortality. A total of 4683 patients were evaluated; acute kidney injury developed in 1261 patients (26.9%; 95% confidence interval [CI], 25.6 to 28.2), and severe acute kidney injury developed in 543 patients (11.6%; 95% CI, 10.7 to 12.5). Severe acute kidney injury conferred an increased risk of death by day 28 after adjustment for 16 covariates (adjusted odds ratio, 1.77; 95% CI, 1.17 to 2.68); death occurred in 60 of the 543 patients (11.0%) with severe acute kidney injury versus 105 of the 4140 patients (2.5%) without severe acute kidney injury (P<0.001). Severe acute kidney injury was associated with increased use of mechanical ventilation and renal-replacement therapy. A stepwise increase in 28-day mortality was associated with worsening severity of acute kidney injury (P<0.001 by log-rank test). Assessment of acute kidney injury according to the plasma creatinine level alone failed to identify acute kidney injury in 67.2% of the patients with low urine output. Acute kidney injury is common and is associated with poor outcomes, including increased mortality, among critically ill children and young adults. (Funded by the Pediatric Nephrology Center of Excellence at Cincinnati Children’s Hospital Medical Center and others; AWARE ClinicalTrials.gov number, NCT01987921.)

BACKGROUND AND OBJECTIVE: Nephrotoxic medication exposure represents a common cause of acute kidney injury (nephrotoxin-AKI) in hospitalized children. Systematic serum creatinine (SCr) screening has not been routinely performed in children receiving nephrotoxins, potentially leading to underestimating nephrotoxin-AKI rates. We aimed to accurately determine nephrotoxin exposure and nephrotoxin-AKI rates to drive appropriate interventions in non–critically ill hospitalized children. METHODS: We conducted a prospective quality improvement project implementing a systematic electronic health record (EHR) screening and decision support process (trigger) at a single quaternary pediatric hospital. Patients were all noncritically ill hospitalized children receiving an intravenous aminoglycoside for ≥3 days or ≥3 nephrotoxins simultaneously (exposure). Pharmacists recommended daily SCr monitoring in exposed patients. AKI was defined by the modified pediatric Risk, Injury, Failure, Loss and End-stage Renal Disease criteria (≥25% decrease in estimated creatinine clearance). We developed 4 novel metrics: exposure rate per 1000 patient-days, AKI rate per 1000 patient-days, AKI rate (%) per high nephrotoxin admission, and AKI days per 100 exposure days (AKI intensity). RESULTS: This study included 21 807 patients accounting for 27 711 admissions. A total of 726 (3.3%) unique exposed patients accounted for 945 hospital admissions (6713 patient-days). AKI occurred in 25% of unique exposed patients and 31% of exposure admissions (1974 patient-days). Our EHR-driven SCr nephrotoxin-AKI surveillance process was associated with a 42% reduction in AKI intensity. CONCLUSIONS: Nephrotoxin-AKI rates are high in noncritically ill children; systematic screening for nephrotoxic medication exposure and AKI detection was accomplished reliably through an EHR based trigger tool.

Summary: The incidence rate of AKI is increasing across the spectrum of hospitalized children and adults. Given the increased morbidity and mortality associated with AKI, significant research effort has been appropriately focused on standardizing AKI definitions, identifying risk factors, and discovering and validating novel, earlier structural biomarkers of kidney injury. In addition, a growing body of evidence demonstrates that AKI is a risk factor for the future development or accelerated progression of CKD. Unfortunately, prospective observational studies have not consistently followed survivors of episodes of AKI for longitudinal outcomes after hospital discharge, which could lead to ascertainment bias in terms of over- or underestimation of CKD development. Furthermore, data show that clinical follow-up of AKI survivors is low. This lack of systematic study and clinical follow-up represents a potential missed opportunity to prevent chronic disease after an acute illness and improve outcomes. Therefore, prospective study of transitions of care after episodes of AKI is needed to identify which patients are at risk for CKD development and to optimally target therapeutic interventions.