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Objective: To evaluate serum creatinine (SCr) patterns and the development of acute kidney injury (AKI), as potential biomarkers of necrotizing enterocolitis (NEC)., Study Design: Retrospective chart review of preterm infants with and without NEC born 23-32 weeks gestation admitted to Nationwide Children's Hospital NICU. Medical versus surgical NEC was determined by radiographic and clinical findings. Available inpatient SCr levels obtained on days 8 through 365 were included., Result: In this cohort, 77 NEC and a randomly selected group of 82 non-NEC infants met inclusion criteria. Fifteen of the 70 (21.4%) with NEC met criteria for AKI versus 0 of 43 (0.0%) without NEC. One of the 13 with AKI had AKI within 7 days prior to NEC diagnosis (7.7%)., Conclusion: AKI is more prevalent in infants with NEC. The temporal association between AKI and NEC could not be evaluated due to inconsistent SCr surveillance and should be evaluated in future studies., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Childhood acute lymphoblastic leukemia (ALL) fortunately has high survival rates, and understanding longer term implications of therapy is critical. In this study, we aimed to investigate kidney health outcomes by assessing the prevalence of renal dysfunction and hypertension (HTN) in children with ALL at 1-5 years after ALL diagnosis., Methods: This was a single-center, cross-sectional study of children with ALL who were 1-5 years post diagnosis. Glomerular filtration rate (GFR) measurements were calculated, and urine samples were collected to assess for protein/creatinine and albumin/creatinine. Blood pressure (BP) was determined by standard oscillometric technique, and children ≥6 years of age were eligible for ambulatory blood pressure monitoring (ABPM)., Results: Forty-five patients enrolled in the study, and 21 completed ABPMs. Fifteen patients (33%, 95% CI: 20%-49%) developed acute kidney injury (AKI) at least once. Thirteen (29%, 95% CI: 16%-44%) had hyperfiltration, and 11 (24%) had abnormal proteinuria and/or albuminuria. Prevalence of HTN based on clinic measurements was 42%. In the 21 ABPM patients, 14 had abnormal results (67%, 95% CI: 43%-85%), with the majority (11/21) demonstrating abnormal nocturnal dipping pattern., Conclusions: Among children with ALL, there is a high prevalence of past AKI. The presence of hyperfiltration, proteinuria, and/or albuminuria at 1-5 years after ALL diagnosis suggests real risk of developing chronic kidney disease (CKD) over time. There is a high prevalence of HTN on casual BP readings and even higher prevalence of abnormal ABPM in this group. The high prevalence of impaired nocturnal dipping by ABPM indicates an increased risk for future cardiovascular or cerebral ischemic events., (© 2022 Wiley Periodicals LLC.)

Background: To define the incidence of acute kidney injury (AKI), chronic kidney disease (CKD), and hypertension (HTN) in pediatric patients diagnosed with acute lymphoblastic leukemia (ALL) over a recent 9-year period., Methods: This study is a retrospective cohort study of all pediatric patients diagnosed with ALL at Nationwide Children's Hospital from January 1, 2008, to December 31, 2016. Patient demographic and clinical data including serum creatinine and blood pressure were collected at diagnosis up to 9 years post diagnosis., Results: A total of 222 patients were identified for this study. The overall incidence of AKI in our cohort was high, with 101 subjects (45.5%, CI 38.8-52.3%) developing AKI at least once. CKD status could only be determined in 214 patients due to limited later GFR data. The incidence of CKD was low with only 5 of 214 patients developing CKD (2.3%, CI: 0.8-5.4%). The overall incidence of HTN at diagnosis was 45.6% (95% CI: 59.1-72%), and at 1 month post diagnosis was 65.8% (95% CI: 59.1-72.0%). Chronic HTN could only be determined in 216 patients due to limited blood pressure data. Chronic HTN was noted in 34.3% of patients (74/216, 95% CI: 28-41%)., Conclusions: Among children with ALL, the incidence of AKI is relatively high at the time of diagnosis. However, development of CKD is relatively rare, suggesting good mid-term kidney prognosis. There is a high incidence of HTN at the time of diagnosis, 1 month post diagnosis, and chronic HTN that often goes untreated. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Data from adult and pediatric literature have shown an association between albumin levels and AKI. Whether hypoalbuminemia and neonatal AKI are associated has not been studied., Methods: We evaluated the association of albumin with early (during the first postnatal week) and late (after the first postnatal week) AKI for 531 neonates from the Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN) database and for 3 gestational age (GA) subgroups: < 29, 29 to < 36, and ≥ 36 weeks GA., Results: Low albumin levels were associated with increased odds of neonatal AKI; for every 0.1 g/dL decrease in albumin, the odds of late AKI increased by 12% on continuous analysis. After adjustment for potential confounders, neonates with albumin values in the lowest quartiles (< 2.2 g/dL) had an increased odds of early [Adjusted Odd Ratio (AdjOR) 2.5, 95% CI = 1.1-5.3, p < 0.03] and late AKI [AdjOR 13.4, 95% CI = 3.6-49.9, p < 0.0001] compared to those with albumin in the highest quartile (> 3.1 g/dL). This held true for albumin levels 2.3 to 2.6 g/dL for early [AdjOR 2.5, 95% CI = 1.2-5.5, p < 0.02] and late AKI [AdjOR 6.4, 95% CI = 1.9-21.6, p < 0.01]. Albumin quartiles of (2.7 to 3.0 g/dL) were associated with increased odds of late AKI. Albumin levels of 2.6 g/dL and 2.4 g/dL best predicted early (AUC = 0.59) and late AKI (AUC = 0.64), respectively. Analysis of albumin association with AKI by GA is described., Conclusions: Low albumin levels are independently associated with early and late neonatal AKI. Albumin could be a potential modifiable risk factor for neonatal AKI., (© 2021. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Acute kidney injury (AKI) in preterm infants is associated with prolonged hospitalization and high mortality. Diuretic therapy has been used to enhance urine output in preterm infants with AKI. Treatment with diuretics, prescription patterns, and relationship with length of stay (LOS), mechanical ventilation (MV), and mortality in preterm infants who also had AKI have not been fully evaluated., Methods: This multicenter retrospective study used the Pediatric Hospital Information System database. We included 2121 preterm infants with AKI diagnosis from 46 hospital Neonatal Intensive Care Units (NICUs) born <37 weeks gestational age (GA). Treatment with diuretics, practice patterns across 46 NICUs in the USA, and associated outcomes including LOS, MV, and mortality were evaluated., Results: Seventy-six percent of infants received at least one dose of diuretics (median treatment 18 days). Diuretic prescription varied significantly across hospitals and ranged from 42 to 96%. Diuretics were used more frequently in infants with younger GA and smaller birth weight. Infants with older GA who received diuretics at or before 28 days postnatally had worse survival even after adjusting for known confounders., Conclusions: Preterm infants with AKI diagnosis were frequently treated with diuretics. Moreover, infants with younger GA and smaller birth weight were more likely to receive diuretics. Worse survival in infants with older GA who received diuretics could be the result of more underlying severe illness in these infants and not the cause of more severe illness. Prospective studies are needed to best determine patient safety and outcomes with diuretic treatment in preterm infants with AKI. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2021. IPNA.)

Background: Studies in adults showed a relationship between low hemoglobin (Hb) and acute kidney injury (AKI). We performed this study to evaluate this association in newborns., Methods: We evaluated 1891 newborns from the Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN) database. We evaluated the associations for the entire cohort and 3 gestational age (GA) groups: <29, 29-<36, and ≥36 weeks' GA., Results: Minimum Hb in the first postnatal week was significantly lower in neonates with AKI after the first postnatal week (late AKI). After controlling for multiple potential confounders, compared to neonates with a minimum Hb ≥17.0 g/dL, both those with minimum Hb ≤12.6 and 12.7-14.8 g/dL had an adjusted increased odds of late AKI (aOR 3.16, 95% CI 1.44-6.96, p = 0.04) and (aOR 2.03, 95% CI 1.05-3.93; p = 0.04), respectively. This association was no longer evident after controlling for fluid balance. The ability of minimum Hb to predict late AKI was moderate (c-statistic 0.68, 95% CI 0.64-0.72) with a sensitivity of 65.9%, a specificity of 69.7%, and a PPV of 20.8%., Conclusions: Lower Hb in the first postnatal week was associated with late AKI, though the association no longer remained after fluid balance was included., Impact: The current study suggests a possible novel association between low serum hemoglobin (Hb) and neonatal acute kidney injury (AKI). The study shows that low serum Hb levels in the first postnatal week are associated with increased risk of AKI after the first postnatal week. This study is the first to show this relationship in neonates. Because this study is retrospective, our observations cannot be considered proof of a causative role but do raise important questions and deserve further investigation. Whether the correction of low Hb levels might confer short- and/or long-term renal benefits in neonates was beyond the scope of this study.

Background: We evaluated the epidemiology of fluid balance (FB) over the first postnatal week and its impact on outcomes in a multi-center cohort of premature neonates from the AWAKEN study., Methods: Retrospective analysis of infants <36 weeks' gestational age from the AWAKEN study (N = 1007). FB was defined by percentage of change from birth weight., Outcome: Mechanical ventilation (MV) at postnatal day 7., Results: One hundred and forty-nine (14.8%) were on MV at postnatal day 7. The median peak FB was 0% (IQR: -2.9, 2) and occurred on postnatal day 2 (IQR: 1,5). Multivariable models showed that the peak FB (aOR 1.14, 95% CI 1.10-1.19), lowest FB in first postnatal week (aOR 1.12, 95% CI 1.07-1.16), and FB on postnatal day 7 (aOR 1.10, 95% CI 1.06-1.13) were independently associated with MV on postnatal day 7. In a similar analysis, a negative FB at postnatal day 7 protected against the need for MV at postnatal day 7 (aOR 0.21, 95% CI 0.12-0.35)., Conclusions: Positive peak FB during the first postnatal week and more positive FB on postnatal day 7 were independently associated with MV at postnatal day 7. Those with a negative FB at postnatal day 7 were less likely to require MV.

Background: In sick neonates admitted to the NICU, improper fluid balance can lead to fluid overload. We report the impact of fluid balance in the first postnatal week on outcomes in critically ill near-term/term neonates., Methods: This analysis includes infants ≥36 weeks gestational age from the Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) study (N = 645). Fluid balance: percent weight change from birthweight., Primary Outcome: mechanical ventilation (MV) on postnatal day 7., Results: The median peak fluid balance was 1.0% (IQR: -0.5, 4.6) and occurred on postnatal day 3 (IQR: 1, 5). Nine percent required MV at postnatal day 7. Multivariable models showed the peak fluid balance (aOR 1.12, 95%CI 1.08-1.17), lowest fluid balance in 1st postnatal week (aOR 1.14, 95%CI 1.07-1.22), fluid balance on postnatal day 7 (aOR 1.12, 95%CI 1.07-1.17), and negative fluid balance at postnatal day 7 (aOR 0.3, 95%CI 0.16-0.67) were independently associated with MV on postnatal day 7., Conclusions: We describe the impact of fluid balance in critically ill near-term/term neonates over the first postnatal week. Higher peak fluid balance during the first postnatal week and higher fluid balance on postnatal day 7 were independently associated with MV at postnatal day 7.