Optimizing the AKI definition during first postnatal week using Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) cohort.

BACKGROUND: Neonates with serum creatinine (SCr) rise ≥0.3 mg/dL and/or ≥50% SCr rise are more likely to die, even when controlling for confounders. These thresholds have not been tested in newborns. We hypothesized that different gestational age (GA) groups require different SCr thresholds. METHODS: Neonates in Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) with ≥1 SCr on postnatal days 1-2 and ≥1 SCr on postnatal days 3-8 were assessed. We compared the mortality predictability of SCr absolute (≥0.3 mg/dL) vs percent (≥50%) rise. Next, we determine usefulness of combining absolute with percent rise. Finally, we determined the optimal absolute, percent, and maximum SCr thresholds that provide the highest mortality area under curve (AUC) and specificity for different GA groups. RESULTS: The ≥0.3 mg/dL rise outperformed ≥50% SCr rise. Addition of percent rise did not improve mortality predictability. The optimal SCr thresholds to predict AUC and specificity were ≥0.3 and ≥0.6 mg/dL for ≤29 weeks GA, and ≥0.1 and ≥0.3 mg/dL for >29 week GA. The maximum SCr value provides great specificity. CONCLUSION: Unique SCr rise cutoffs for different GA improves outcome prediction. Percent SCr rise does not add value to the neonatal AKI definition.

Improving parental mental health in the perinatal period: A review and analysis of quality improvement initiatives.

Parental mental health is an essential sixth vital sign that, when taken into consideration, allows clinicians to improve clinical outcomes for both parents and infants. Although standards exist for screening, referral, and treatment for perinatal mood and anxiety disorders (PMADs), they are not reliably done in practice, and even when addressed, interventions are often minimal in scope. Quality improvement methodology can accelerate the implementation of interventions to address PMADs, but hurdles exist, and systems are not well designed, particularly in pediatric inpatient facilities. In this article, we review the effect of PMADs on parents and their infants and identify quality improvement interventions that can increase screening and referral to treatment of parents experiencing PMADs.

A novel urinary biomarker profile to identify acute kidney injury (AKI) in critically ill neonates: a pilot study.

BACKGROUND: The goal of this study was to assess the value of a urinary biomarker profile comprised of neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-2 (FGF-2), and epidermal growth factor (EGF), to detect acute kidney injury (AKI) in critically ill neonates. METHODS: We conducted a prospective cohort pilot study of at-risk neonates treated in a level IIIC neonatal intensive care unit (NICU) with therapeutic hypothermia (HT) (n = 25) or extracorporeal membrane oxygenation (ECMO) (n = 10). Urine was collected at baseline, 48 h of illness, and > 24 h post-recovery of their corresponding treatments. Control samples were collected from 27 healthy newborns. The data were expressed as urinary concentrations and values normalized for urinary creatinine. AKI was defined as the presence of oliguria >24 h and/or elevated serum creatinine (SCr), or the failure to improve the estimated creatinine clearance (eCCL) by >50% post-recovery. Non-parametric statistical tests and ROC analyses were used to interpret the data. RESULTS: Fifteen at-risk newborns had AKI. In the first 48 h of illness, the urinary levels of NGAL and FGF-2 had high sensitivity but poor specificity to identify neonates with AKI. At recovery, low urinary EGF levels identified neonates with AKI with a sensitivity of 74% and specificity of 84%. Overall, in the early stages of a critical illness, the urinary levels of NGAL and FGF-2 were sensitive, but not specific, to identify neonates at risk of AKI. Low EGF levels post-recovery identified critically ill neonates with AKI. CONCLUSIONS: These findings require validation in larger prospective studies.

A pilot study of urinary fibroblast growth factor-2 and epithelial growth factor as potential biomarkers of acute kidney injury in critically ill children.

BACKGROUND: Acute kidney injury (AKI) increases the morbidity of critically ill children. Thus, it is necessary to identify better renal biomarkers to follow the outcome of these patients. This prospective case-control study explored the clinical value of a urinary biomarker profile comprised of neutrophil gelatinase lipocalin (uNGAL), fibroblast growth factor-2 (uFGF-2), and epidermal growth factor (uEGF) to follow these patients. METHODS: Urine samples were collected from 21 healthy children, and 39 critically ill children (mean age 7.5 years ± 6.97 SD) admitted to a pediatric intensive care unit with sepsis or requiring extra corporeal membrane oxygenation (ECMO). uNGAL, uFGF-2, and uEGF levels were measured using ELISA kits during the first 24 h of admission to PICU, at peak of illness, and upon resolution of the critical illness. RESULTS: On admission, the uNGAL and uFGF-2 levels were increased, and the uEGF levels were decreased, in critically ill children with AKI (n = 19) compared to those without AKI (n = 20), and healthy controls. A biomarker score using the combined cut-off values of uNGAL, uFGF-2, and uEGF (AUC = 0.90) showed the highest specificity to identify children with AKI, relative to each biomarker alone. uNGAL and uFGF-2 on admission showed high sensitivity and specificity to predict mortality (AUC = 0.82). CONCLUSIONS: The biomarker profile comprised of uNGAL, uFGF-2, and uEGF increased the specificity to detect AKI in critically ill children, when compared to each biomarker used alone. uNGAL and uFGF-2 may also predict the risk of death. Further validation of these findings in a large sample size is warranted.

Improving Documentation of Pain Reassessment after Pain Management Interventions in the NICU.

Background: Neonates exposed to painful procedures require pain assessment and reassessment using nonverbal scales. Nurses perform initial assessments routinely, but reassessment is variable. The goal was to increase pain reassessments in neonates with a previous score of 4 or higher within 60 minutes from 50% to 75% within 12 months. Methods: After identifying key drivers, we tested several interventions using the IHI's Model for Improvement. The outcome measure was the rate of reassessments within 1 hour after scoring ≥4 on the Neonatal Pain Agitation and Sedation Scale (N-PASS). Duration of time between scoring and intervention was documented. Interventions included electronic health record (EHR) changes, direct communication with bedside nurses through text messages and emails, in-person education, and a yearly competency module. The process measure was the number of messages/emails to staff. Sedation scores were the balancing measure. Results: Baseline compliance was 50% with significant variability. A centerline shift occurred after the first intervention. After the first four interventions in the following 3 months, a 29% total increase occurred. Overall time-lapse between reassessments decreased from 102 to 90 minutes. Overall sedation scores decreased from -2.5 during the baseline to -1.7 during the sustain period. The goal of 75% pain reassessments was achieved and sustained for two years. Conclusions: Automated tools such as the trigger report provided data that increased noncompliance visibility. Real-time and personalized reminders and education improved awareness and set the tone for culture change. Electronic health record reminders for reassessments and standardized annual education helped in sustaining change.

Role of circulating fibroblast growth factor-2 in lipopolysaccharide-induced acute kidney injury in mice.

Fibroblast growth factor-2 (FGF-2) is an angiogenic growth factor involved in renal growth and regeneration. Previous studies in rodents revealed that single intrarenal injections of FGF-2 improved the outcome of acute kidney injury (AKI). Septic children usually show elevated plasma levels of FGF-2, and are at risk of developing AKI. However, the role of circulating FGF-2 in the pathogenesis of AKI is not well understood. We have developed a mouse model to determine how FGF-2 released into the circulation modulates the outcome of AKI induced by lipopolysaccharide (LPS). Young FVB/N mice were infected with adenoviruses carrying a secreted form of human FGF-2 or control LacZ vectors. Subsequently, when the circulating levels of FGF-2 were similar to those seen in septic children, mice were injected with a non-lethal dose of LPS or control buffer. All mice injected with LPS developed hypotension and AKI, from which they recovered after 5 days. FGF-2 did not improve the outcome of AKI, and induced more significant renal proliferative and apoptotic changes during the recovery phase. These findings suggest that circulating FGF-2 may not necessarily prevent the development or improve the outcome of AKI. Moreover, the renal accumulation of FGF-2 might cause further renal damage.

A New Approach to Recognize Neonatal Impaired Kidney Function.

INTRODUCTION: Previous studies in term newborns with hypoxic ischemic encephalopathy showed that the rate of serum creatinine (SCr) decline during the first week of life could be used to identify newborns with impaired kidney function (IKF) who are missed by standard definitions of neonatal acute kidney injury (nAKI). METHODS: Retrospective review of the medical records of 329 critically ill newborns ≥27 weeks of gestational age (GA) admitted to a level 4 neonatal intensive care unit (NICU). We tested the hypothesis that the rate of SCr decline combined with SCr thresholds provides a sensitive approach to identify term and preterm newborns with IKF during the first week of life. RESULTS: Excluding neonates with nAKI, an SCr decline <31% by the seventh day of life, combined with an SCr threshold ≥0.7 mg/dl, recognized newborns of 40 to 31 weeks of GA with IKF. An SCr decline <21% combined with an SCr threshold ≥0.8 mg/dl identified newborns of 30 to 27 weeks of GA with IKF. Neonates with IKF (∼17%), like those with nAKI (7%), showed a more prolonged hospital stay and required more days of mechanical ventilation, vasoactive drugs, and diuretics, when compared with the controls. Changes in urine output did not distinguish newborns with IKF. CONCLUSION: The rate of SCr decline combined with SCr thresholds identifies newborns with IKF during the first week of life. This distinctive group of newborns that is missed by standard definitions of nAKI, warrants close monitoring in the NICU to prevent further renal complications.

Urinary biomarkers of kidney diseases in HIV-infected children.

A significant number of children infected with the human immunodeficiency virus 1 (HIV-1) virus all over the world are at risk of developing renal diseases that could have a significant impact on their treatment and quality of life. It is necessary to identify children undergoing the early stages of these renal diseases, as well as the potential renal toxicity that could be caused by antiretroviral drugs, in order to prevent the development of cardiovascular complications and chronic renal failure. This article describes the most common renal diseases seen in HIV-infected children, as well as the value and limitations of the clinical markers that are currently being used to monitor their renal function and histological damage in a noninvasive manner. In addition, we discuss the progress made during the last 10 years in the discovery and validation of new renal biomarkers for HIV-infected children and young adults. Although significant progress has been made during the early phases of the biomarkers discovery, more work remains to be done to validate the new biomarkers in a large number of patients. The future looks promising, however, the new knowledge needs to be integrated and validated in the context of the clinical environment where these children are living.