The Utility of Urinary NGAL as an Alternative for Serum Creatinine to Detect Acute Kidney Injury in Infants Exposed to Nephrotoxic Medications in the Neonatal Intensive Care Unit.

INTRODUCTION: Nephrotoxic medication (NTM) exposure is commonly associated with acute kidney injury (AKI) in the neonatal intensive care unit (NICU). Baby Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a quality improvement program that assesses for AKI in those exposed to NTM with daily serum creatinine (SCr) levels. However, blood draws for SCr are invasive and have clinical disadvantages. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a promising indicator of AKI. We tested the hypothesis that uNGAL could reliably screen for NTM-AKI in the Baby NINJA program. METHODS: This two-center prospective study screened 174 NICU subjects, of whom 148 met screening criteria from January 29, 2019, to September 18, 2020. Daily SCr and urine samples were obtained for up to 7 days of NTM exposure plus 2 days after exposure ended or end of AKI. AKI was defined by a SCr rise of 50% from baseline. The highest uNGAL obtained was evaluated to determine its relationship to the diagnosis of AKI. Logistic regression models were used to determine optimal uNGAL cutoffs. RESULTS: The negative predictive value of a uNGAL value ≥250 ng/mL was 96.8% (95% CI = 93.3-100%). Urine NGAL ≥400 ng/mL demonstrated the highest ROC-AUC value of 0.72 with a positive likelihood risk for AKI of 2.76 (1.39-4.13). DISCUSSION/CONCLUSION: We propose that uNGAL could be used to screen for NTM-AKI and thus replace many blood draws needed in those exposed to NTM. The ideal uNGAL threshold requires further investigation in infants.

Implementation Strategies for Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action) to Prevent Neonatal Medication-Induced Kidney Injury.

Acute kidney injury (AKI) is a common complication among patients admitted to the neonatal intensive care unit. Nephrotoxic medications (NTMs) are known to increase the incidence of AKI, but the use of these -medications is often unavoidable. Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action) is a -quality improvement (QI) project that may be implemented at individual institutions and aims to systematically identify AKI in neonates and infants receiving NTMs. The purpose of this review is to describe nephrotoxic AKI in the neonatal population, introduce the Baby NINJA QI project and its potential to reduce neonatal AKI, and outline strategies for effective implementation of Baby NINJA.

Risk of chronic kidney disease in children who developed acute kidney injury secondary to nephrotoxic medication exposure in infancy.

INTRODUCTION: Nephrotoxic medication (NTM) is one of the common causes of acute kidney injury (AKI) in critically ill infants. Current knowledge about the long-term effects of NTM exposure and associated AKI during the neonatal period and early infancy is limited. Hence, we aimed to explore the risk of chronic kidney disease (CKD) after NTM-AKI in this age group. METHODS: We performed a cross-sectional study including children 2-7 years of age, who had a history of high NTM exposure during NICU hospitalization. Cases and controls were defined as children who developed AKI and who did not develop AKI after NTM exposure, respectively. The primary outcome of interest was to explore the prevalence of composite CKD. In addition, we explored differences in urinary biomarker kidney injury molecule-1 (KIM-1) between the groups. RESULTS: We enrolled 48 children, 18 cases and 30 controls in which 25/48 (52%) had at least one finding of CKD. The composite CKD outcome tended to be higher in cases vs controls (61.1% vs. 46.6%, odds ratio = 1.79 (95% confidence interval 0.54-5.8)); however, this was not statistically significant. Median urinary KIM-1 value trended higher in controls, 0.367(0.23-0.59) vs. 0.20 (IQR 0.11-0.47), which was not statistically significant. CONCLUSION: In this study, 52% of children exposed to NTM had at least one marker of CKD at a median age of 5 years. Multicenter, large prospective studies are needed to improve our understanding of the natural course of NTM-AKI and to determine risk factors and strategies to reduce CKD in this high-risk population.

Infant Safe Sleep Knowledge, Attitudes, and Behaviors by Physicians at an Academic Children's Hospital.

Sudden unexpected infant death (SUID) is the leading cause of death for infants. Physician advice on safe sleep is an important source of information for families. We sought to evaluate the safe sleep knowledge, attitudes, and behaviors of physicians by distributing a cross-sectional survey at a freestanding children's hospital. The survey included demographics, knowledge items, attitudinal assessment, and frequency of providing safe sleep guidance. Multivariable linear regression and logistic regression were used to evaluate associations between variables. 398 physicians were surveyed with 124 responses (31%). Females, those who received safe sleep training, and those who see infants in daily practice had higher knowledge scores. Physicians with higher knowledge scores had more positive attitudes toward safe sleep and provided safe sleep education to patients more often. Our study underlies the importance of education and repeated exposure in forming positive attitudes toward safe sleep recommendations and leads to increased provision of safe sleep guidance.

Improving Adherence to Safe Sleep Guidelines for Hospitalized Infants at a Children's Hospital.

INTRODUCTION: Sudden unexpected infant deaths are a major problem nationally. We had poor adherence to safe sleep recommendations locally at our institution. Given the significance of this problem, hospital administration at a tertiary children's hospital tasked a multidisciplinary group of faculty and staff with improving sleep environments for hospitalized infants. METHODS: Our safe sleep task force implemented targeted interventions using the American Academy of Pediatrics policy statement as the gold standard and based on hospital data to address areas of greatest nonadherence to recommendations. We aimed to improve weekly average adherence to 95% over 12 months. A proportions process control chart (p-chart) tracked average weekly adherence over a 52-week time frame. In addition, we performed Student's t-testing to evaluate differences in adherence over time. RESULTS: There was a significant improvement in overall adherence to safe sleep recommendations from baseline (M = 70.8%, SD 21.6) to end of study period (M = 94.7%, SD 10.0) [t(427) = -15.1, P ≤ 0.001]. Crib audits with 100% adherence increased from a baseline (M = 0%, SD 0) to the end of the study period M = 70.4%, SD = 46) [t(381)= -21.4, P ≤ 0.001]. This resulted in two trend shifts on the p-chart using Institute for Healthcare Improvement control chart rules. CONCLUSIONS: Targeted interventions using QI methodology led to significant increases in adherence to safe sleep guidelines. Notable improvements in behavior indicated significant changes in safe sleep culture. We also noted continued adherence in follow-up audits reflecting sustainability.

Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action): Reduction of Nephrotoxic Medication-Associated Acute Kidney Injury in the Neonatal Intensive Care Unit.

OBJECTIVE(S): To test if acute kidney injury (AKI) is preventable in patients in the neonatal intensive care unit and if infants at high-risk of nephrotoxic medication-induced AKI can be identified using a systematic surveillance program previously used in the pediatric non-intensive care unit setting. STUDY DESIGN: Quality improvement project that occurred between March 2015 and September 2017 in a single center, level IV neonatal intensive care unit. Infants were screened for high-risk nephrotoxic medication exposure (≥3 nephrotoxic medication within 24 hours or ≥4 calendar days of an intravenous [IV] aminoglycoside). If infants met criteria, a daily serum creatinine (SCr) was obtained until 2 days after end of exposure or end of AKI, whichever occurred last. The study was divided into 3 eras: pre-Nephrotoxic Injury Negated by Just-in-time Action (NINJA), initiation, and sustainability. Differences for 5 metrics across 3 eras were compared: SCr surveillance, high nephrotoxic medication exposure rate (per 1000 patient-days), AKI rate (per 1000 patient-days), nephrotoxin-AKI percentage, and AKI intensity (number of AKI days per 100 susceptible patient-days). RESULTS: Comparing the initiation with sustainability era, there was a reduction in high nephrotoxic medication exposures from 16.4 to 9.6 per 1000 patient-days (P = .03), reduction in percentage of nephrotoxic medication-AKI from 30.9% to 11.0% (P < .001), and reduction in AKI intensity from 9.1 to 2.9 per 100 susceptible patient-days (P < .001) while maintaining a high SCr surveillance rate. This prevented 100 AKI episodes during the 18-month sustainability era. CONCLUSION(S): A systematic surveillance program to identify high-risk infants can prevent nephrotoxic-induced AKI and has the potential to prevent short and long-term consequences of AKI in critically ill infants.

The Association of Intraventricular Hemorrhage and Acute Kidney Injury in Premature Infants from the Assessment of the Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) Study.

BACKGROUND: Acute kidney injury (AKI) and intraventricular hemorrhage (IVH) are common in premature infants. We previously demonstrated that infants with AKI have a higher hazards ratio to develop grade ≥2 IVH when controlling for confounders. However, that single-center study was unable to show an overall association. OBJECTIVES: To test the hypothesis that infants diagnosed with AKI have an increased risk of IVH independent of variables associated with both AKI and IVH, we performed a study on 825 infants from the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study (a 24-center multinational retrospective cohort). METHOD: A neonatal modified KDIGO definition of AKI was used based on serum creatinine (SCr) and/or urine output criteria. Baseline SCr was defined as the lowest previous value. IVH was diagnosed with head ultrasounds. RESULTS: AKI was documented in 22.2% (183/825) of infants and IVH in 14.3% (118/825). Infants with AKI (n = 183) were more likely to have IVH (26.8%, 49/183) than those without AKI (n= 642) who had IVH (10.7%, 69/642, p < 0.0001). After controlling for 5-min Apgar score, vasopressor support within the first week of age, and gestational age, infants with AKI had 1.6 times higher adjusted odds to develop any grade IVH (95% CI 1.04-2.56). Furthermore, infants of gestational age of 22-28 weeks had 1.9 times higher adjusted odds to develop IVH (OR 1.87, 95% CI 1.08-3.23). CONCLUSIONS: We present the first multicenter evaluation of the association between AKI and IVH in premature infants showing a significant independent association between AKI and IVH. Development of strategies to reduce AKI may also reduce IVH.

Menkes disease complicated by concurrent Koolen-de Vries syndrome (17q21.31 deletion).

BACKGROUND: Koolen-de Vries (KdV) syndrome is caused by a 17q21.31 deletion leading to clinical symptoms of hypotonia and developmental delay and can present with abnormal hair texture. Menkes disease is an X-linked recessive inherited disease caused by pathogenic variants in ATP7A, which leads to profound copper deficiency. METHOD: We identified an infant male who presented with prematurity, hypotonia, and dysmorphic features for whom a family history of clinical Menkes disease was revealed after discussion with the clinical genetics team. RESULTS: Although initial first-tier genetic testing identified Kdv syndrome (17q21.31 syndrome), the family history led the team to consider a second diagnostic possibility, and testing of ATP7A revealed a pathogenic variant (c.601C>T, p.R201X). CONCLUSION: Menkes disease and KdV syndrome may both present with hypotonia and abnormal hair, in addition to seizures and failure to thrive. While these genetic conditions have overlapping clinical features, they have different natural histories and different therapeutic options. Here, we report on a patient affected with both disorders and review the diagnostic and therapeutic difficulties this presented.

Neonatal Acute Kidney Injury and the Risk of Intraventricular Hemorrhage in the Very Low Birth Weight Infant.

Despite improvements in survival of premature infants, many have comorbid conditions. The role of the kidney in multiorgan dysfunction is unclear, particularly in regard to intraventricular hemorrhage (IVH). We hypothesized that infants diagnosed with acute kidney injury (AKI) have an increased risk of IVH independent of gestational age (GA) and other variables associated with both comorbidities. This prospective cohort study consisted of 125 infants with a birth weight ≤1,200 g and/or GA ≤31 weeks. A definition of AKI was used from KDIGO, not including urine output as nonoliguria is common in this population. IVH was based on serial head ultrasounds. Neonates with AKI had a higher trend towards having IVH compared to those without [14/35 (40%) vs. 22/83 (26.5%), p = 0.1]. Infants with AKI were more likely to have stage 2 IVH or higher than those without AKI [12/36 (33.3%) vs. 6/82 (7.3%); p < 0.01]. AKI was associated with a 3.6-fold increased risk of a grade 2 or higher IVH [hazard ratio (HR) 3.55, 95% confidence interval (CI) 1.39-9.07] and over 4-fold increase in risk of a grade 3 or higher IVH (HR 4.34, 95% CI 1.43-13.21). While there was no association between AKI and IVH overall, those with AKI had a higher hazard ratio to develop a grade 2 or higher IVH even when controlling for birth weight, antenatal steroid use, and 5-min Apgar score. Future studies are indicated to expand sample size and to control for other clinical variables that could be associated with both AKI and IVH.