Objective:To characterize gestational age (GA)-specific serum creatinine (SCr) trajectories among level IV neonatal intensive care unit (NICU) infants and develop an interactive interpretation tool. Study Design:We analyzed ADVANCE database records linking kidney-specific data with Children's Hospitals Neonatal Consortium clinical data from ten level IV NICUs (2010-2022). Infants with ≥ 1 SCr measurement (DOL 1-365) were included. GA-specific trajectories were generated for DOL 1-28 and week of life 1-16; an interactive tool was developed for clinical use. Result:Among 34,306 infants contributing 390,612 SCr measurements, SCr trajectories differed by GA. Peak SCr ranged from 0.93 mg/dL (IQR 0.80-1.10) at 22-24 weeks' GA (DOL 4) to 0.76 mg/dL (IQR 0.65-0.90) among term infants (DOL 2), declining to a similar nadir (~ 0.20-0.23 mg/dL) across GA groups. Conclusion:SCr trajectories vary by GA and postnatal age in this population. These trajectories and the accompanying tool provide context for interpreting SCr values.

Determine whether acute kidney injury (AKI) is associated with subsequent late-onset infection (LOI) among extremely low gestational age newborns (ELGAN). Secondary analysis of participants in the Preterm Erythropoietin for Neuroprotection Trial. Infants surviving ≥7 days with sufficient serum creatinine data were included. The primary outcome was any LOI, starting ≥72 h after AKI. Time-varying Cox proportional hazards modeling estimated adjusted hazard ratios of AKI and LOI. 332/872 (38

IMPACT:The consensus neonatal modified KDIGO definition has been crucial in expanding our understanding of the epidemiology and impact of neonatal AKI. A consensus definition of neonatal AKI remains essential to continuing to advance the field. This manuscript highlights a historical perspective, the strengths, and limitations of the current neonatal AKI definition, and reflects on the optimal characteristics and utility of neonatal AKI definitions. The future of neonatal AKI lies with improved diagnostic precision and consistently incorporating neonatal risk factors into risk stratification incorporating and the deployment of novel biomarkers to aid in earlier identification and improve outcomes in neonatal AKI.

Introduction: Acute kidney injury (AKI) is common in critically ill neonates, including very and extremely low birth weight (VLBW, ELBW) neonates. In severe cases, kidney replacement therapy (KRT) may be warranted. Currently, available KRT devices are only indicated for those weighing >= 2.5 kg and require a double lumen or 2 separate single lumen catheters. We miniaturized the Kirpa Kit manual dialysis device, naming it the Brophy Kit, and we assessed its in vitro clearance and ultrafiltration (UF) performance. Methods: We diluted packed red blood cells to a normal hematocrit (Hct: 31.1%-36.8%) and conducted 12 clearance and 3 UF experiments. A cycle consisted of aspirating 10 ml of blood from the blood bag, passing it through a hemofilter, and returning it in a circular path. For clearance experiments, we tested 4 configurations, with varied timing and volume of saline flushes to refresh the dialysis compartment, then measured blood urea nitrogen (BUN) and potassium concentrations every 5 cycles. For each UF cycle, 1 ml of ultrafiltrate was removed, and Hct was measured every 10 cycles. Results: Median BUN and potassium reduction were 31.0% (interquartile range [IQR]: 17.6-37.9) and 35.0% (IQR: 26.9-41.7), respectively, after 30 clearance cycles. Median Hct increased to 52.6% (IQR: 52.5- 53.8) after 60 UF cycles, more than the expected Hct (47.7%). Conclusion: The Brophy Kit performs in vitro clearance efficiently and UF consistently. The Brophy Kit may address a technological KRT gap for small neonates because of its minimal extracorporeal volume and ability to function with single lumen access.

BACKGROUND:Preterm birth is associated with low nephron endowment, with an increased risk of chronic kidney disease (CKD) later in life. Almost all pregnant women at risk for preterm delivery are given antenatal corticosteroids (ANS) to accelerate lung maturity in preterm neonates. Similar to ANS, postnatal corticosteroids are also given to improve lung function, but the impact on kidney function is unknown. The objective of this study was to determine if duration and timing of postnatal corticosteroids in preterm infants influences kidney function at 24 months corrected age. METHODS:A secondary analysis of the PENUT trial (neonates <28 weeks' gestation) was performed and included surviving participants with serum creatinine measured at 22-26 months corrected gestational age (cGA). Exposure included the presence, type, start date, and duration of postnatal steroids (duration and start date based on postmenstrual age (PMA)). The primary outcome was reduced estimated GFR (GFR <90 ml/min/1.73 m2 at the 24-month CGA timepoint). Outcomes were adjusted for perinatal/neonatal exposures, and neonatal outcomes were compared. RESULTS:Out of 838 surviving infants, 397 (47%) were exposed to any postnatal steroid. Dexamethasone was the most common exposure (n = 238, median start date at day of life (DOL) 27, median duration of 8 days), followed by hydrocortisone (n = 232, median start DOL 13, median duration 17 days). 348 infants were evaluated at 22-26-month follow-up, 61 of whom had reduced GFR. Hydrocortisone duration of 1-7 days had 2.8 (95% CI = 1.06-7.62) times increased odds of reduced GFR at 24 months corrected age. Although overall steroid exposure was not associated with GFR at follow-up, initiation of dexamethasone at ≤25 weeks PMA was associated with 9.39 (95% CI = 1.61-54.71) increased odds of reduced GFR compared to those given dexamethasone at ≥29 weeks. CONCLUSIONS:Although observational, this study supports an association between postnatal steroid timing, duration, and reduced GFR. Further studies are warranted to better understand this association to protect long-term kidney health.

Importance Kidney disease is common in infants admitted to the neonatal intensive care unit (NICU). Despite the risk of chronic kidney disease (CKD) in infants discharged from the NICU, neither evidence- nor expert-based recommendations exist to guide clinical care after discharge. Objective To develop recommendations for risk stratification and kidney health monitoring among infants after discharge from the NICU. Evidence Review At the National Institute of Health-supported Consensus Workshop to Address Kidney Health in Neonatal Intensive Care Unit Graduates meeting conducted in February 2024, a panel of 51 neonatal nephrology experts focused on 3 at-risk groups: (1) preterm infants, (2) critically ill infants with acute kidney injury (AKI), and (3) infants with critical cardiac disease. Using established modified Delphi processes, workgroups derived consensus recommendations. Findings In this modified Delphi consensus statement, the panel developed 10 consensus recommendations, identified gaps in knowledge, and prioritized areas of future research. Principal suggestions include risk stratification at time of hospital discharge, family and clinician education and counseling for subsequent kidney health follow-up, and blood pressure assessment as part of outpatient care. Conclusions and Relevance Preterm infants, critically ill infants with AKI, and infants with critical cardiac disease are at increased risk of CKD. We recommend (1) risk assessment at the time of discharge, (2) clinician and family education, and (3) kidney health assessments based on the degree of risk. Future work should focus on improved risk stratification, identification of early kidney dysfunction, and development of interventions to improve long-term kidney health.

ImportanceKidney disease is common in infants admitted to the neonatal intensive care unit (NICU). Despite the risk of chronic kidney disease (CKD) in infants discharged from the NICU, neither evidence- nor expert-based recommendations exist to guide clinical care after discharge.ObjectiveTo develop recommendations for risk stratification and kidney health monitoring among infants after discharge from the NICU.Evidence ReviewAt the National Institute of Health–supported Consensus Workshop to Address Kidney Health in Neonatal Intensive Care Unit Graduates meeting conducted in February 2024, a panel of 51 neonatal nephrology experts focused on 3 at-risk groups: (1) preterm infants, (2) critically ill infants with acute kidney injury (AKI), and (3) infants with critical cardiac disease. Using established modified Delphi processes, workgroups derived consensus recommendations.FindingsIn this modified Delphi consensus statement, the panel developed 10 consensus recommendations, identified gaps in knowledge, and prioritized areas of future research. Principal suggestions include risk stratification at time of hospital discharge, family and clinician education and counseling for subsequent kidney health follow-up, and blood pressure assessment as part of outpatient care.Conclusions and RelevancePreterm infants, critically ill infants with AKI, and infants with critical cardiac disease are at increased risk of CKD. We recommend (1) risk assessment at the time of discharge, (2) clinician and family education, and (3) kidney health assessments based on the degree of risk. Future work should focus on improved risk stratification, identification of early kidney dysfunction, and development of interventions to improve long-term kidney health.

We aimed to examine temporal changes in the annual rate of acute kidney injury (AKI) in Danish children and associated changes in patient characteristics including potential underlying risk factors. In this population-based cohort study, we used plasma creatinine measurements from Danish laboratory databases to identify AKI episodes in children aged 0–17 years from 2007 to 2021. For each child, the first AKI episode per calendar year was included. We estimated the annual crude and sex- and age-standardized AKI rate as the number of children with an AKI episode divided by the total number of children as reported by census numbers. Using Danish medical databases, we assessed patient characteristics including potential risk factors for AKI, such as use of nephrotoxic medication, surgery, sepsis, and perinatal factors. In total, 14,200 children contributed with 16,345 AKI episodes over 15 years. The mean annual AKI rate was 148 (95

BACKGROUND:Acute kidney injury (AKI) occurs in up to half of infants admitted to the neonatal intensive care unit (NICU) and is associated with increased risks of death and more days of mechanical ventilation, hospitalization, and vasopressor drug support. Our objective was to build a granular relational database to study the impact that AKI has on infants admitted to Level-IV NICUs. METHODS:A relational database was created by linking data from the Children's Hospitals Neonatal Database with AKI-focused data from electronic health records from 9 centers. RESULTS:The current cohort consists of 24,870 infants with a median (IQR) gestational age of birth of 37 weeks (32 weeks, 39 weeks), and a median birth weight of 2.720 kg (1.750 kg, 3.310 kg). There was a male predominance with 14,214 (57%) males. In all, 2434 (9.8%) of the mothers were of Hispanic ethnicity. The maternal race breakdown of the cohort was as follows: 741 (3.0%) Asian, 5911 (24%) Black, and 14,945 (60%) White. Overall mortality was 5.8%. CONCLUSION:The ADVANCE relational database is an innovative research tool to rigorously study the epidemiology of AKI in a large national cohort of infants admitted to Level-IV NICUs involved in the Children's Hospital Neonatal Consortium. IMPACT:We used a biomedical informatics approach to build a relational database to study acute kidney injury in infants. We highlight our methodology linking Children's Hospital Neonatal Consortium and electronic health record data from nine neonatal intensive care units. The ADVANCE relational database is a granular and innovative research tool to study risk factors and in-hospital outcomes of acute kidney injury and mortality in a vulnerable patient population.

Objective Although the Accreditation Council for Graduate Medical Education and American Board of Pediatrics (ABP) provide regulations and guidance on fellowship didactic education, each program establishes their own didactic schedules to address these learning needs. Wide variation exists in content, educators, amount of protected educational time, and the format for didactic lectures. This inconsistency can contribute to fellow dissatisfaction, a perceived poor learning experience, and poor attendance. Our objective was to create a Neonatal–Perinatal Medicine (NPM) fellow curriculum based on adult learning theory utilizing fellow input to improve the perceived fellow experience. Study Design A needs assessment of current NPM fellows at Cincinnati Children's Hospital was conducted to guide the development of a new curriculum. Fellow perception of educational experience and board preparedness before and after introduction of the new curriculum was collected. Study period was from October 2018 to July 2021. Results One hundred percent of the fellows responded to the needs assessment survey. A response rate of 100 and 87.5% were noted on mid-curriculum survey and postcurriculum survey, respectively. Key themes identified and incorporated into the curriculum included schedule structure, content, and delivery mode. A new didactic curriculum implementing a consistent schedule of shorter lectures grouped by organ system targeting ABP core content was created. After curriculum implementation, fellows had higher self-perception of board preparedness, and overall improved satisfaction. Conclusion Our positive experience in implementing this curriculum provides a framework for individual programs to implement similar curricula, and could be utilized to aid in development of national NPM curricula. Key Points

Background Access to pediatric dialysis is challenged in low-resource settings by high costs, scarcity of equipment, and lack of qualified personnel availability. We demonstrated the manual Single Lumen Alternating Micro-Batch (mSLAMB) device can remove small solutes in vitro without the need for electricity, batteries or pumps. We developed a new version (Kirpa Kit™) to address some of the technical limitations of mSLAMB. Here we compare the in vitro clearance performance and ease of use of Kirpa Kit™ with that of prior mSLAMB configurations. Methods A mixture of expired packed red blood cells, 0.9% NaCl, urea and heparin was used to test the efficiency of two mSLAMB configurations and Kirpa Kit™ in removing potassium and urea. Clearance was evaluated by measuring percent reduction after 25-minute sessions with each device. A survey was used to evaluate the ease of use of each configuration. Results The Kirpa Kit™ achieved a median urea reduction of 82.4% and potassium reduction of 82.1%, which were higher than those achieved with the best-performing mSLAMB configuration (urea 71.9%, potassium 75.4%). The Kirpa Kit™ was easier to use with a shorter perceived time of use than the mSLAMB. Conclusions The Kirpa Kit™, evolution of mSLAMB, is easy to use and may have improved efficacy, making it an optimal candidate for in vivo testing.

This cross-sectional analyzes knowledge of acute kidney disease (AKI) diagnosis and associated risks among caregivers of hospitalized children.

BACKGROUND:Extremely low gestational age neonates (ELGANs) are at risk for chronic kidney disease. The long-term kidney effects of neonatal caffeine are unknown. We hypothesize that prolonged caffeine exposure will improve kidney function at 22-26 months. METHODS:Secondary analysis of the Preterm Erythropoietin Neuroprotection Trial of neonates <28 weeks' gestation. Participants included if any kidney outcomes were collected at 22-26 months corrected age. Exposure was post-menstrual age of caffeine discontinuation. PRIMARY OUTCOMES:'reduced eGFR' <90 ml/min/1.73 m2, 'albuminuria' (>30 mg albumin/g creatinine), or 'elevated blood pressure' (BP) >95th %tile. A general estimating equation logistic regression model stratified by bronchopulmonary dysplasia (BPD) status was used. RESULTS:598 participants had at least one kidney metric at follow up. Within the whole cohort, postmenstrual age of caffeine discontinuation was not associated with any abnormal measures of kidney function at 2 years. In the stratified analysis, for each additional week of caffeine, the no BPD group had a 21% decreased adjusted odds of eGFR <90 ml/min/1.73m2 (aOR 0.78; CI 0.62-0.99) and the BPD group had a 15% increased adjusted odds of elevated BP (aOR 1.15; CI: 1.05-1.25). CONCLUSIONS:Longer caffeine exposure during the neonatal period is associated with differential kidney outcomes at 22-26 months dependent on BPD status. IMPACT:In participants born <28 weeks' gestation, discontinuation of caffeine at a later post menstrual age was not associated with abnormal kidney outcomes at 22-26 months corrected age. When assessed at 2 years of age, later discontinuation of caffeine in children born <28 weeks' gestation was associated with a greater risk of reduced eGFR in those without a history of BPD and an increased odds of hypertension in those with a history of BPD. More work is necessary to understand the long-term impact of caffeine on the developing kidney.

Acute kidney injury (AKI) is common in hospitalized preterm neonates. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a promising noninvasive AKI biomarker. However, normal values of uNGAL in preterm neonates without AKI are poorly characterized. The objective of this study was to evaluate the current literature to determine normal uNGAL values for preterm neonates without AKI.Systematic review and meta-analysis of all articles published before November 2021 evaluating uNGAL values in preterm neonates without AKI.Of 1,607 studies evaluated for eligibility, 11 were included in the final meta-analysis (210 males, 202 females). uNGAL values were higher in the preterm neonates <29 weeks and ranged between 20.7 and 782.65 ng/mL. Meta mean estimates of gestational age (GA), birthweight, and neutrophil gelatinase-associated lipocalin were 29.4 weeks (95% confidence interval [CI]: 28.8-30.0), 1,241 g (95% CI: 1,111-1,372), and 148.9 ng/mL (95% CI: 48-231), respectively.In limited studies, a wide range of uNGAL values in preterm neonates without AKI are reported. Future studies should identify normal uNGAL values in preterm neonates using larger cohorts by GA and birthweight. · Urinary NGAL is a promising noninvasive biomarker of neonatal AKI.. · A wide range of uNGAL is reported in preterm neonates but the baseline values are not well defined.. · Urine NGAL values are higher in extremely preterm compared with preterm neonates..

Kidney replacement therapy (KRT) is used to treat children and adults with acute kidney injury (AKI), fluid overload, kidney failure, inborn errors of metabolism, and severe electrolyte abnormalities. Peritoneal dialysis and extracorporeal hemodialysis/filtration can be performed for different durations (intermittent, prolonged intermittent, and continuous) through either adaptation of adult devices or use of infant-specific devices. Each of these modalities have advantages and disadvantages, and often multiple modalities are used depending on the scenario and patient-specific needs. Traditionally, these therapies have been challenging to deliver in infants due the lack of infant-specific devices, small patient size, required extracorporeal volumes, and the risk of hemodynamic stability during the initiation of KRT. In this review, we discuss challenges, recent advancements, and optimal approaches to provide KRT in hospitalized infants, including a discussion of peritoneal dialysis and extracorporeal therapies. We discuss each specific KRT modality, review newer infant-specific devices, and highlight the benefits and limitations of each modality. We also discuss the ethical implications for the care of infants who need KRT and areas for future research.

Background Daily serum creatinine monitoring protocols for acute kidney injury (AKI) are invasive and may lead to surveillance resistance. We aimed to understand if use of urine neutrophil gelatinase-associated lipocalin (uNGAL) could increase high-risk nephrotoxic medication (NTMx) associated AKI screening adherence in neonates. Methods Statistical process control methods prior to and post implementation were trended. The primary outcome, screening adherence, was defined as either daily serum creatinine or uNGAL assessment through 2 days post high-risk NTMx exposure. Results 1291 monitoring days from the pre-implementation era (4/2020-6/2021) were compared to1377 monitoring days from the post-era (6/2021-10/2022). AKI screening adherence increased (81 to 92%) following implementation of optional uNGAL screening. Urine NGAL accounted for 35% of screening obtained. Use of uNGAL resulted in a 40% reduction in blood sampling for serum creatinine. Conclusions Incorporation of uNGAL as a complementary screening tool to serum creatinine demonstrated sustained increased AKI surveillance in our Baby NINJA monitoring program.