Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study

Background: Single-center studies suggest that neonatal acute kidney injury (AKI) is associated with poor outcomes. However, inferences regarding the association between AKI, mortality, and hospital length of stay are limited due to the small sample size of those studies. In order to determine whether neonatal AKI is independently associated with increased mortality and longer hospital stay, we analyzed the Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) database. Methods: All neonates admitted to 24 participating neonatal intensive care units from four countries (Australia, Canada, India, United States) between January 1 and March 31, 2014, were screened. Of 4273 neonates screened, 2022 (47·3%) met study criteria. Exclusion criteria included: no intravenous fluids ≥48 hours, admission ≥14 days of life, congenital heart disease requiring surgical repair at <7 days of life, lethal chromosomal anomaly, death within 48 hours, inability to determine AKI status or severe congenital kidney abnormalities. AKI was defined using a standardized definition -i.e., serum creatinine rise of ≥0.3 mg/dL (26.5 mcmol/L) or ≥50% from previous lowest value, and/or if urine output was <1 mL/kg/h on postnatal days 2 to 7. Findings: Incidence of AKI was 605/2022 (29·9%). Rates varied by gestational age groups (i.e., ≥22 to <29 weeks =47·9%; ≥29 to <36 weeks =18·3%; and ≥36 weeks =36·7%). Even after adjusting for multiple potential confounding factors, infants with AKI had higher mortality compared to those without AKI [(59/605 (9·7%) vs. 20/1417 (1·4%); p< 0.001; adjusted OR=4·6 (95% CI=2·5-8·3); p=<0·0001], and longer hospital stay [adjusted parameter estimate 8·8 days (95% CI=6·1-11·5); p<0·0001]. Interpretation: Neonatal AKI is a common and independent risk factor for mortality and longer hospital stay. These data suggest that neonates may be impacted by AKI in a manner similar to pediatric and adult patients

Pediatric idiopathic retroperitoneal fibrosis

Retroperitoneal fibrosis (RPF) is a very rare disease that is even more rare in the pediatric population. Even less common are idiopathic pediatric cases of retroperitoneal fibrosis, with a majority of reported pediatric retroperitoneal fibrosis cases being associated with secondary etiologies. We present an 11-year-old Caucasian female that was diagnosed with idiopathic retroperitoneal fibrosis using magnetic resonance imaging (MRI) to work-up severe bilateral hydronephrosis that was identified with retroperitoneal ultrasound. Given the uncommon nature of this serious condition, we present this case to illustrate the importance for physicians to include retroperitoneal fibrosis in the differential diagnosis of a pediatric patient presenting with obstructive urinary findings and understand the utility of using MRI to diagnosis and monitor this disease. Keywords: Idiopathic retroperitoneal fibrosis, Pediatric, MR

Safety, Feasibility, and Impact of Enalapril on Cardiorespiratory Physiology and Health in Preterm Infants with Systemic Hypertension and Left Ventricular Diastolic Dysfunction

Neonatal hypertension has been increasingly recognized in premature infants with bronchopulmonary dysplasia (BPD); of note, a sub-population of these infants may have impaired left ventricular (LV) diastolic function, warranting timely treatment to minimize long term repercussions. In this case series, enalapril, an angiotensin-converting enzyme (ACE) inhibitor, was started in neonates with systemic hypertension and echocardiography signs of LV diastolic dysfunction. A total of 11 patients were included with birth weight of 785 ± 239 grams and gestational age of 25.3 (24, 26.1) weeks. Blood pressure improvement was noticed within 2 weeks of treatment. Improvement in LV diastolic function indices were observed with a reduction in Isovolumic Relaxation Time (IVRT) from 63.1 ± 7.2 to 50.9 ± 7.4 msec and improvement in the left atrium size indexed to aorta (LA:Ao) from1.73 (1.43, 1.88) to 1.23 (1.07, 1.29). Neonatal systemic hypertension is often underappreciated in ex-preterm infants and may be associated with important maladaptive cardiac changes with long term implications. It is biologically plausible that identifying and treating LV diastolic dysfunction in neonates with systemic hypertension may have a positive modulator effect on cardiovascular health in childhood and beyond

Maternal Hypertension Disorders and Neonatal Acute Kidney Injury: Results from the AWAKEN Study

Abstract Objective  This study aimed to examine the association between maternal hypertension (HTN) exposure and neonatal acute kidney injury (AKI). Study Design  Retrospective cohort study of 2,162 neonates admitted to 24 neonatal intensive care units (NICUs). Neonates were classified into the following exposure groups: any maternal HTN, chronic maternal HTN, preeclampsia/eclampsia, both, or neither. Demographics, clinical characteristics, and AKI status were compared using Chi-square and analysis of variance. General estimating logistic regression was used to estimate adjusted odds ratios and included a stratified analysis for site of delivery. Result  Neonates exposed to any maternal HTN disorder had a tendency toward less overall and early AKI. When stratified by inborn versus outborn, exposure to both maternal HTN disorders was associated with a significantly reduced odds of early AKI only in the inborn neonates. Conclusion  Exposure to maternal HTN, especially preeclampsia/eclampsia superimposed on chronic HTN, was associated with less likelihood of early AKI in the inborn group. Key Points Maternal HTN is associated with less neonatal AKI. Maternal HTN category is variably associated with AKI. Inborn status is an important contributor to this association

Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates: Design of a Retrospective Cohort Study.

INTRODUCTION: Acute kidney injury (AKI) affects ~30% of hospitalized neonates. Critical to advancing our understanding of neonatal AKI is collaborative research among neonatologists and nephrologists. The Neonatal Kidney Collaborative (NKC) is an international, multidisciplinary group dedicated to investigating neonatal AKI. The AWAKEN study (Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates) was designed to describe the epidemiology of neonatal AKI, validate the definition of neonatal AKI, identify primary risk factors for neonatal AKI, and investigate the contribution of fluid management to AKI events and short-term outcomes. METHODS AND ANALYSIS: The NKC was established with at least one pediatric nephrologist and neonatologist from 24 institutions in 4 countries (USA, Canada, Australia, and India). A Steering Committee and four subcommittees were created. The database subcommittee oversaw the development of the web-based database (MediData Rave™) that captured all NICU admissions from 1/1/14 to 3/31/14. Inclusion and exclusion criteria were applied to eliminate neonates with a low likelihood of AKI. Data collection included: (1) baseline demographic information; (2) daily physiologic parameters and care received during the first week of life; (3) weekly snapshots ; (4) discharge information including growth parameters, final diagnoses, discharge medications, and need for renal replacement therapy; and (5) all serum creatinine values. ETHICS AND DISSEMINATION: AWAKEN was proposed as human subjects research. The study design allowed for a waiver of informed consent/parental permission. NKC investigators will disseminate data through peer-reviewed publications and educational conferences. DISCUSSION: The purpose of this publication is to describe the formation of the NKC, the establishment of the AWAKEN cohort and database, future directions, and a few lessons learned. The AWAKEN database includes ~325 unique variables and \u3e4 million discrete data points. AWAKEN will be the largest, most inclusive neonatal AKI study to date. In addition to validating the neonatal AKI definition and identifying risk factors for AKI, this study will uncover variations in practice patterns related to fluid provision, renal function monitoring, and involvement of pediatric nephrologists during hospitalization. The AWAKEN study will position the NKC to achieve the long-term goal of improving the lives, health, and well-being of newborns at risk for kidney disease

Advances in Neonatal Acute Kidney Injury

In this state-of-the-art review, we highlight the major advances over the last 5 years in neonatal acute kidney injury (AKI). Large multicenter studies reveal that neonatal AKI is common and independently associated with increased morbidity and mortality. The natural course of neonatal AKI, along with the risk factors, mitigation strategies, and the role of AKI on short- and long-term outcomes, is becoming clearer. Specific progress has been made in identifying potential preventive strategies for AKI, such as the use of caffeine in premature neonates, theophylline in neonates with hypoxic-ischemic encephalopathy, and nephrotoxic medication monitoring programs. New evidence highlights the importance of the kidney in “crosstalk” between other organs and how AKI likely plays a critical role in other organ development and injury, such as intraventricular hemorrhage and lung disease. New technology has resulted in advancement in prevention and improvements in the current management in neonates with severe AKI. With specific continuous renal replacement therapy machines designed for neonates, this therapy is now available and is being used with increasing frequency in NICUs. Moving forward, biomarkers, such as urinary neutrophil gelatinase–associated lipocalin, and other new technologies, such as monitoring of renal tissue oxygenation and nephron counting, will likely play an increased role in identification of AKI and those most vulnerable for chronic kidney disease. Future research needs to be focused on determining the optimal follow-up strategy for neonates with a history of AKI to detect chronic kidney disease

Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study.

Background: Single-center studies suggest that neonatal acute kidney injury (AKI) is associated with poor outcomes. However, inferences regarding the association between AKI, mortality, and hospital length of stay are limited due to the small sample size of those studies. In order to determine whether neonatal AKI is independently associated with increased mortality and longer hospital stay, we analyzed the Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) database. Methods: All neonates admitted to 24 participating neonatal intensive care units from four countries (Australia, Canada, India, United States) between January 1 and March 31, 2014, were screened. Of 4273 neonates screened, 2022 (47·3%) met study criteria. Exclusion criteria included: no intravenous fluids ≥48 hours, admission ≥14 days of life, congenital heart disease requiring surgical repair atlife, lethal chromosomal anomaly, death within 48 hours, inability to determine AKI status or severe congenital kidney abnormalities. AKI was defined using a standardized definition -i.e., serum creatinine rise of ≥0.3 mg/dL (26.5 mcmol/L) or ≥50% from previous lowest value, and/or if urine output was/kg/h on postnatal days 2 to 7. Findings: Incidence of AKI was 605/2022 (29·9%). Rates varied by gestational age groups (i.e., ≥22 to=47·9%; ≥29 to=18·3%; and ≥36 weeks =36·7%). Even after adjusting for multiple potential confounding factors, infants with AKI had higher mortality compared to those without AKI [(59/605 (9·7%) vs. 20/1417 (1·4%); p\u3c 0.001; adjusted OR=4·6 (95% CI=2·5-8·3); p= Interpretation: Neonatal AKI is a common and independent risk factor for mortality and longer hospital stay. These data suggest that neonates may be impacted by AKI in a manner similar to pediatric and adult patients. Funding: US National Institutes of Health, University of Alabama at Birmingham, Cincinnati Children\u27s, University of New Mexico