4th International Symposium on Acute Kidney Injury in Children

Abstract

Background: Acute kidney injury (AKI) that requires continuous kidney replacement therapy (CKRT) is a highly lethal condition in critically ill patients. Despite improvements in acute care and dialysis therapies, the mortality rate from the past four decades has not improved. In a previous single treatment arm study of children >20kg on CKRT treated with SCD, 12/16 subjects survived to ICU discharge, all of whom were dialysis independent by day 60 [1]. We now report outcomes in findings the first 6 treated patients < 20 kg.

3
Methods: 6 center US study of SCD in children that weigh between ≥10 and ≤ 20kg, have a clinical diagnosis of AKI requiring CKRT and at least one non-renal organ failure. With these subjects the SCD was integrated post CKRT hemofilter, changed daily, and circuit ionized calcium (iCa) maintained <0.4 mmol/L. Subjects received SCD treatment for up to 10 days or CKRT discontinuation, whichever came first. Results: 7 patients (2F/5M) have been enrolled since 07/2021. Six patients (Age 1.7 -10.4 years. PRISM-2 Score range = 12-27) received SCD therapy. Patients received SCD on a PRISMAFLEX™ or on a PRISMAX™ machine. Circuit iCa was targeted at <0.4 mmol/L during 90% of therapy. All surviving patients demonstrated renal recovery after SCD therapy, coming off all forms of KRT within 5 days post SCD therapy. Of the patients that have reached day 60, all were dialysis independent. One patient died after SCD therapy had ended but before ICU discharge. An additional patient was enrolled but did not start SCD treatment because iCa was not in range from citrate intolerance. No SCD-related serious adverse events have been reported. Conclusion: Our initial findings suggest that SCD is safe in critically ill pediatric patients weighing between 10-20kg and appears to have probable benefit.  Background: Nephrotoxic medication exposure is associated with neonatal Acute Kidney Injury (AKI). Nephrotoxic Injury Negated by Just-in-time Action in neonates (Baby NINJA) is an automated screening process aimed to reduce nephrotoxic medication (NTM) exposure, AKI prevalence and intensity. Rather than daily serum draws for creatinine (sCr) screening, urine neutrophil gelatinase-associated lipocalin (uNGAL) is a less invasive alternative screening tool for neonatal AKI. The impact of elevated uNGAL values on therapeutic drug monitoring (TDM) is currently unknown.
Methods: This is a single center observational study following the introduction of uNGAL into the Baby NINJA screening algorithm in June of 2021. Urine NGAL is used unless serum labs are being obtained for other indications. The uNGAL is reviewed daily and if >150 ng/dL, then screening is transitioned to daily sCr monitoring until 2 days following the end of NTM exposure or 7 days. Infants less than 12 months of age who were admitted to the CCHMC NICU with uNGAL concentrations and on aminoglycosides and/ or vancomycin from 6/15/2021 -7/31/2022 were included in this study. The primary aims were to describe the current practice for TDM in patient with uNGAL concentrations >150 and to determine if there is a correlation between these values and incidence of supratherapeutic drug levels.
Results: A total of 15 episodes in 13 subjects met inclusion criteria. The median birth weight was 0.7 kg (IQR: 0.55, 1.365 kg) and median gestational age was 30 weeks (IQR: 23, 31 weeks). Elevated uNGAL values ranged from 175 to 8778 ng/mL. Three of 15 (20%) TDM levels were obtained prior to standard practice secondary to elevated uNGAL levels (221, 2088, and 8778 ng/mL). Out of the 15 TDM levels, seven levels were within goal range, two were supratherapeutic, and six were subtherapeutic. None of the TDM levels drawn early were supratherapeutic. Background: There is insufficient data to inform antimicrobial dosing for patients requiring continuous kidney replacement therapy (CKRT), a critically ill population for whom . MB-102 is a novel fluorescent marker of glomerular filtration rate (GFR) whose transdermally-detectable fluorescence decay is an accurate measurement of GFR in patients with GFR as low as 15 mL/min/1.73 m 2 . MB-102 (relmapirazin) concentrations and fluorescence have previously been shown to correlate with effluent meropenem concentrations in an in vivo model of CKRT using nephrectomized pigs, but the correlation of MB-102 concentrations with drugs with higher degrees of protein binding, such as cefepime, is unknown. Methods: A mock continuous veno-venous hemofiltration (CVVH) circuit was constructed using a polyethersulfone filter with selectivity for molecules up to 12 kDa. A reservoir solution was prepared containing equimolar concentrations of MB-102 with meropenem or cefepime in a mixture of human plasma and phosphate-buffered saline. The ultrafiltrate was collected at intervals from 30 to 360 minutes while the retentate was re-circulated to the reservoir for refiltration. Concentrations of MB-102, meropenem, and cefepime in the ultrafiltrate were assessed by high performance liquid chromatography. Results: MB-102, cefepime, and meropenem were all detectable in the ultrafiltrate throughout the experiment. The ratio of meropenem to MB-102 remained relatively constant throughout (range 0.97-1.20, mean 1.17, SD 0.097; r 2 for linear correlation 0.99). The ratio of cefepime to MB-102 was initially low at 0.20 from 0-30 mins, then rose to 1.51 from 120-180 minutes before falling to 0.92 from 300-360 minutes.
Conclusions: A mock CVVH circuit was successfully designed for use in studying ultrafiltrate concentrations of antibiotics and MB-102. Meropenem, with negligible protein binding, was filtered at a similar rate to MB-102. Cefepime, which has 20% protein binding, was initially filtered less than, then more than, then at the same rate as MB-102, potentially due to initial variability in the local concentration of free cefepime followed by establishment of an equilibrium between cefepime filtration and protein unbinding. Future studies should compare MB-102 filtration to that of drugs with more protein binding to explore the utility of MB-102 in predicting drug concentrations for patients on CKRT. Keywords: CKRT, pharmacokinetics, GFR, MB-102, fluorescent tracer agent Corresponding Author: H. Rhodes Hambrick, MD Figure 1. Schematic of the mock CVVH system, from the Pellicon XL operating manual. The "feed" solution was the reservoir containing MB-102, plasma, phosphate-buffered saline, and human plasma. This solution was pumped to the filter; the filtrate (here labeled "waste") was collected, and its contents were analyzed serially as described, while the retentate was returned to the reservoir for recirculation. Background: In a small study investigating mineralocorticoid-responsive circulatory collapse and neonatal acute kidney injury (AKI), it was found that postnatal steroids (PNS) may impact AKI due to relative mineralocorticoid insufficiency [1]. We aimed to investigate associations between PNS exposure and AKI in a large cohort of very low birthweight (VLBW, BW <1500 grams) neonates and hypothesized VLBW neonates exposed to PNS will have fewer episodes of AKI than those without this exposure.

Abstract 011
Characterization of C-C motif chemokine ligand 14 (CCL14) for prediction of persistent AKI in critically ill children.
Katie Brandewie, Jeffrey Alten, Stuart Goldstein, Kat Gist Acute kidney injury (AKI) is a common problem affecting more than 25% of critically ill children, including those following cardiac surgery. Until recently, there was limited data on the temporal associations of AKI with outcomes. Indeed, AKI lasting a brief period (24-48 hours) was considered the same as an AKI episode lasting more than 48 hours. Fortunately, most episodes of AKI in critically ill children resolve quickly. However, in approximately 5-10% of critically ill children, AKI persists. Persistent AKI is defined as AKI lasting longer than 72 hours and is a risk factor for long-term sequala, including chronic kidney disease, infection/sepsis, and death. It remains difficult to modify the clinical course of patients with AKI, which may be related to the inability to identify those at risk for persistent injury. Recent risk stratification tools such as the renal angina index and cardiac renal angina index have been developed to identify children at risk for severe day 3 AKI when assessed early in the intensive care unit course. Unfortunately, these tools do not identify children who are at risk for persistent AKI. There is a significant knowledge gap in identifying patients who are at risk for persistent AKI.
Urinary C-C motif chemokine ligand 14 (CCL14) is a small molecule member of the chemokine family that plays a role in leukocyte chemotaxis and is involved in tissue injury and repair processes. CCL14 is an important chemokine for monocyte and macrophage recruitment, both of which are believed to play important roles in kidney tissue damage and development of persistent kidney dysfunction. Furthermore, CCL14 has been shown to be an inflammatory marker identifying the risk of developing end-stage renal disease in diabetics. Recently, urinary C-C motif chemokine ligand 14 (CCL14) was identified as a biomarker predictive of persistent AKI in critically ill adults. CCL14 outperformed other biomarkers measured in the serum and urine for the prediction of stage 3 persistent AKI with an AUC of 0.83. Similarly, risk for renal replacement therapy and/or death at 90 days increased with tertiles of CCL14 concentration. Whether CCL14 predicts persistent severe AKI in critically ill children is unknown. The performance of CCL14 in critically ill children will be evaluated in the following specific aims: Aim 1. To determine the performance of CCL14 for predicting persistent severe acute kidney injury in critically ill children undergoing cardiac surgery. Hypothesis 1. CCL14 will be highly predictive of persistent severe AKI in children undergoing cardiac surgery. Approach: All patients who have consented to the Heart Institute biorepository will be considered for inclusion. Study patients will be included if they have moderate to severe AKI (KDIGO stage 2 or 3 as defined by urine output or creatinine) based on a preoperative baseline for creatinine or urine output criteria. Control patients will be included as patients without AKI who are matched 1:1 by age and surgical complexity (by STAT category) to study patients.
Patients without a urine sample within 36 hours of CS-AKI diagnosis will be excluded. One urine sample from within the first 36 hours for each included patient will be analyzed for CCL14. The performance of CCL14 will be evaluated by determining the sensitivity, specificity, NPV, PPV and AUC. Persistent severe AKI will be defined as: 1) stage 2 or 3 AKI which lasts ≥ 72 hours or 2) death with 30 days of cardiac surgery or 3) stage 2 or 3 with initiation of kidney replacement therapy within 7 days. These criteria have been modified from the original adult studies based on several factors: 1) mortality rates in pediatric cardiac surgery are low, even with AKI, 2) initiation of kidney replacement therapy in children is generally later than in adults, including that mortality rates are urine samples will be collected within 36 hours of stage 2 or 3 AKI. This study will serve as a pilot and feasibility study to provide preliminary data for future prospective studies. Aim 2. To determine the performance of CCL14 for predicting persistent severe acute kidney injury in critically ill children admitted to the pediatric intensive care unit. Hypothesis 2. CCL14 will be highly predictive of persistent severe AKI in critically ill children.
Approach: This will be a secondary analysis of the AKI-CHERUB (Acute kidney injury in children expected by renal angina and urinary biomarkers) study. Study patients will be included if they have moderate to severe AKI (KDIGO stage 2 or 3 as defined by urine output or creatinine) based on a preoperative baseline for creatinine or urine output criteria. Control patients will be included as patients without AKI who are matched 1:1 by age and surgical complexity (by STAT category) to study patients. Patients without a urine sample within 36 hours of moderate to severe AKI diagnosis will be excluded. One urine sample from within the first 36 hours for each included patient will be analyzed for CCL14. The performance of CCL14 will be evaluated by determining the sensitivity, specificity, NPV, PPV and AUC. Persistent severe AKI will be defined as: 1) stage 2 or 3 AKI which lasts ≥ 72 hours or 2) death with 30 days of cardiac surgery or 3) stage 2 or 3 with initiation of kidney replacement therapy within 7 days. Similar to aim 1, this is a pilot and feasibility aim, from which prospective studies can be developed and the findings validated.

Abstract 012
Understanding potential social determinants of health in non-ICU children exposed to high nephrotoxic The kidney and central nervous system are strongly interconnected [1]. In preterm neonates, acute kidney injury (AKI) has been independently associated with increased rates and severity of intraventricular hemorrhage (IVH) [2]. Similarly, children with chronic kidney disease (CKD) have been shown to have abnormal brain architecture and function [3]. Prior near-infrared spectroscopy (NIRS) tissue oxygenation studies in critically ill neonates have not evaluated differences in Cerebral regional Somatic Oxygenation (CrSO 2 ) based on AKI status. The objective of this study was to evaluate CrSO 2 trends in preterm neonates with and without AKI. Methods: We retrospectively evaluated the CrSO 2 values of 35 neonates bor n less t han 32 weeks' gest ation who were prospectively enrolled in a continuous NIRS monitor ing study in t he f irst week [4]. AKI was deter mined by t he modif ied neonatal  Figure 1 with the peak difference seen at 5 days of age. Conclusions: In this small pilot analysis, neonates with AKI had lower cerebral oxygenation compared to those without AKI. This data highlights the possibility that cerebral tissue perfusion or oxygen utilization may be affected by AKI independent of brain injury. Larger prospective studies are needed to determine the extent to which AKI affects cerebral oxygenation as well as the timing of these changes. Future preterm neonatal NIRS and AKI studies should include short and long-term neurodevelopmental outcomes to evaluate if prevention of AKI may also protect the brain and cognitive function.

Figure 1: Cerebral oxygenation by AKI Status
In the following figure the x axis is time from birth in hours while the y axis represents cerebral oxygenation percentage. The lines represent the median while the shaded area around each line represents the interquartile range. The AKI group has the dotted line and dotted shaded region. The peak difference in the two groups occurs after 96 hours and before 144 hours.

Abstract 016
Investigating the association between renal tissue oxygenation and development of AKI in preterm neonates Matthew W. Background: Neonatal acute kidney injury (AKI) is classically defined by elevations in serum creatinine (SCr) and decreases in urine output and is associated with short-and long-term consequences [1]. Monitoring Renal regional Saturation of Oxygen (RrSO 2 ) with nearinfrared spectroscopy (NIRS) can potentially diagnose AKI noninvasively before changes in traditional markers of kidney function thereby creating a therapeutic window for intervention [2]. We sought to evaluate the relationship between RrSO 2 changes and SCr during the first week of age for preterm neonates born at < 32 weeks gestational age (GA increase in AKI risk (95% CI: 1.1-2.6; p = 0.016). The association between AKI risk and mean %RrSO2 is shown in Figure 1. Conclusions: Decreases in mean RrSO 2 in neonates born at < 32 weeks GA were associated with an increased risk of AKI, like single center studies [3,4]. Further prospective studies are necessary to determine whether RrSO 2 changes can accurately detect AKI and correlate with urinary biomarkers of kidney injury. Future studies should focus on early interventions and therapies that can improve renal oxygenation and evaluate if these changes affect short-and long-term kidney outcomes.

Figure 1: Renal Oxygenation and Probability of Acute Kidney Injury
Association between mean %RrSO2 (horizontal axis) and probability of developing AKI (vertical axis). Individual mean %RrSO2 values are indicated by circular points for 8 infants who developed AKI (probability 1; top edge) and the other 101 who didn't (probability 0; bottom edge). Solid line shows increasing probability with decreasing mean %RrSO2 and 95% confidence interval as surrounding dashed lines.

Background:
The CArdio-Renal PEdiatric DIalysis Emergency Machine (Carpediem™, Medtronic, United States) is a dialysis device designed to provide continuous kidney replacement therapy (CKRT) safely to neonates and infants. Understanding single center use and best practice will be incredibly challenging as we anticipate its use to be important, yet rare. Thus, we created a multicenter multidisciplinary quality improvement and research registry dedicated to informing best practices and treatment strategies to improve outcomes. Methods: The collaborative was established with 7 sites that were the first to offer Carpediem™ therapy in the United States with plans to expand nationally and ultimately internationally. Specific aims of the collaborative include describing variations in education, CKRT prescription and delivery in neonates, and establishing a registry for use in quality improvement and benchmarking efforts. Multidisciplinary representation at each site is encouraged. Research aims include understanding short-and long-term outcomes 1 3 with a focus on growth and development. Institutional Review Board approval was obtained with intent to enroll all patients receiving Carpediem™ at all participating sites. Results: To date, 22 centers have joined ICONIC with representation including nursing leadership, pharmacists, dietitians, nephrologists, pediatric, cardiac and neonatal intensivists, advanced practice providers, and fellows. A subject database using Research Electronic Data Capture (REDCap) tools, and a web-based electronic real-time dashboard for observing collaborative and individual quality metrics have been created and are hosted by Cincinnati Children's Hospital Medical Center. Prospective REDCap data being collected includes but is not limited to demographics and diagnosis, Carpediem™ prescription, daily fluid balance, and short-and long-term outcomes. Additionally, a biorepository is available for urine, serum, and effluent specimens. Alternating monthly meetings occur between the ICONIC steering committee composed of the initial 7 core sites and overall collaborative sites. Collectively, 10 centers have provided over 30 patients with Carpediem™ therapy. As centers become more established, we aim to analyze data for variation and identification of best practices. Conclusions: Multidisciplinary, multicentered collaboration is critical to understanding Carpediem™ best practices secondary to its infrequency. Results: Ten of 22 sites reported ability to provide Car-pediem™. Nine sites completed the survey. Carpediem™ is offered at all sites in the pediatric ICU with 5 sites additionally in the neonatal ICU. A collaborative nursing model was the most used (n=6), most commonly with dialysis and critical care (n=4). All, but two sites reported that bedside RNs had a role related to providing Carpediem™. Median ratio of Carpediem™ trained RNs for every unit bed was 1:1. Median ratio of Carpediem™ trained RNs to ICU total RNs was 1:4 (range 1:10 and 4:10). Nursing-to-patient ratios were predominantly 1:1, although 3 sites had at least one ICU with 2:1. Table 1 demonstrates initial nursing education requirements with 3 sites currently requiring annual competencies. Conclusions: Standards for ideal nursing educational requirements and care delivery models are limited and vary amongst institutions. Understanding initial and ongoing educational requirements and how it influences the quality of delivered therapy and patient outcomes will help inform best practices related to CKRT in the future. Injury Negated by Just-in-time Action), has demonstrated significant reductions of NTM-AKI in the NICU [2]. The QI program systematically screens for AKI in those exposed to three or more NTM in a 24-hour period, or an intravenous aminoglycoside or intravenous vancomycin for ≥72 hours or ≥4 calendar days. Current protocol advises daily serum creatinine (SCr) levels. While the Baby NINJA program has demonstrated sustained results over multiple years, a venipuncture for daily SCr measurements is invasive and is associated with both personnel healthcare costs and increases in neonatal pain scale scores [3]. Urinary neutrophil gelatinase associated lipocalin (uNGAL) is a marker of renal tubular injury and has been associated with some NTM-AKI events [4,5]. We tested the hypothesis that uNGAL could reliably screen for AKI in Baby  Background: The incidence of thrombocytopenia in neonates receiving extracorporeal life support (ECLS) with and without concurrent continuous renal replacement therapy (CRRT) and associated complications have not been well described. We aimed to evaluate associations between CRRT, severe thrombocytopenia (platelets <50,000), and outcomes in neonates receiving ECLS and identify predictors of severe thrombocytopenia.

Methods:
We conducted a single-center chart review of neonates who received ECLS 07/01/14 -03/01/20. Provider discretion dictated CRRT use in the pediatric and cardiac intensive care units (PICU and PCICU, respectively); all patients in the neonatal ICU (NICU) received CRRT. We evaluated associations between CRRT, severe thrombocytopenia, and outcomes (ECLS duration, length of stay (LOS), and mortality) using Fisher's exact, Chi-squared, Student's t, and independent-samples median tests, as appropriate. Exploratory classification and regression tree (CART) analysis was performed to identify optimal predictors of severe thrombocytopenia including characteristics that differed between those with and without severe thrombocytopenia (CRRT, birthweight, ICU location  The manual single lumen alternating microbatch hemodiafiltration (mSLAMB) system is a closedloop dialysis system designed to provide kidney support in emergency situations (e.g., fluid overload, hyperkalemia, acidemia). If done repeatedly in small batches at high flow rates, this system can achieve clearance levels comparable to traditional renal replacement therapy (RRT) 1 . The purpose of this system is to help patients with acute kidney injury (AKI) in austere environments at a low cost (<$25). The manual circuit requires no electricity or batteries and uses a more modest vascular access than traditional modalities. Methods: Nephrectomized pigs (n=4, 14-16kg) were treated with SLAMB manual dialysis to assess removal of uremic toxins and an exogenous florescent tracer. Various RRT modalities were attempted including hemofiltration with and without predilution as well as hemodiafiltration with variations on dialysate flow based on adjusting height of circuit elements. Eight to sixteen cycles using batch volumes of 100-150ml were completed on each animal. Samples were taken periodically to analyze clearance of toxins from blood as well as quantify cleared molecules in dialysate. Results: All analytes were shown to be removed across the dialyzer with each micro batch evaluated. Potassium clearances of 4 to 9 ml/min were achieved. The exogenous florescent tracer was shown to be cleared from the systemic blood with subsequent cycles. High dialysate flows yielded higher clearances as well as passive fluid removal. With this configuration we removed up to 250mL of fluid and 15 mmol of potassium with eight cycles, approximately an hour of treatment. Conclusion: Electrolyte derangements and volume overload remain life threating emergencies in low resource settings. With the mSLAMB system, micro-batch processing was successful at removing a significant fluid volume and also effective at clearing uremic toxins and the exogenous florescent tracer. These studies demonstrate proof of concept for efficacy of mSLAMB in treatment of AKI by providing removal of potassium as well as excess fluid, such that additional stabilizing therapies, such as isotonic bicarbonate solutions can safely be administered. Background: Acute kidney injury (AKI) remains a cause of preventable deaths in low resource settings due to prohibitive costs and lack of basic dialysis access. A single lumen alternating micro-batch (SLAMB) dialysis technique performs kidney replacement therapy (KRT) using single lumen access, a low-cost set of bags and tubing, premade fluids, and a dialysis filter. We have previously shown that a manual variation of SLAMB (mSLAMB) works without electricity, a battery, or a pump. We hypothesized that mSLAMB can perform diffusive clearance efficiently, and a simple, reliable, and safe protocol can bring dialysis to a population who previously did not have it. Methods: Bags of expired packed red blood cells mixed with crystalloid solution were made to desired sizes (0.5-2L) and hematocrits (low vs normal) to simulate infant, toddler, and pediatric blood volumes. Bags were spiked with 1-5 grams of urea and anticoagulated with heparin. A Static diffusion Technique (with 5 second flushes of dialysis fluid before each filter pass) and a Dynamic diffusion Technique (with varying volumes of dialysis fluid running through the filter during a pass) were trialed and urea and potassium clearance were measured. The difference between the 200mL batch volume and volume returned to the blood bag per cycle represented passive ultrafiltration. Results: 5 cycles routinely achieved urea reduction rates (URR) between 17-67% and potassium clearance of 18-60%. The main factor causing these wide ranges in rates was the proportion of batch volume dialyzed to patient volume: 0.5L bags achieved 40-67% URR, 0.8-1.45L bags had 26-56% URR, and 2L bags had 17-31% URR (Figure 1). The Dynamic Technique appears to have had a slightly better URR compared to the Static Technique but required more dialysis fluid and time to change/make effluent and dialysis fluid bags, respectively. Passive ultrafiltration occurred in both Static and Dynamic techniques and the filtered volume depended on the height of the bags from the filter.   [1]. Despite this high incidence, the economic burden of AKI remains understudied. We aimed to compare estimated costs of hospitalization between neonates in the NICU who did and did not develop AKI and identify predictors of AKIassociated costs. We hypothesized neonates who developed AKI would amass significantly more costs than those who did not, and these increased costs would be driven by premature birth, length of hospitalization (LOH), and renal replacement therapy (RRT) receipt. Methods: Using data from the Children's Hospital Association's (CHA) Pediatric Health Information System (PHIS) database, we conducted a retrospective cohort study of neonates in the NICU between 01/01/2015-12/31/2021. Baseline and demographic data were compared between those who did and did not develop AKI using Wilcoxon-Mann Whitney and Chi-squared tests, as appropriate. The adjusted, marginal total cost of hospitalization between those who did and did not develop AKI was estimated using a gamma-distributed log-transformed link function generalized linear model.  Introduction: Cardiac Surgery-associated Acute Kidney Injury (CS-AKI) is common and associated with adverse outcomes. Prior work from the Neonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) demonstrated that only stage 3 AKI was associated with mortality. Given persistent AKI has been associated with worse outcomes in this population, we hypothesize that phenotyping CS-AKI based on duration after the Norwood procedure (NP) will associate with morbidity and mortality. Methods: Multicenter retrospective cohort study from NEPHRON of consecutive neonates undergoing the NP. Patients supported by pre-or post-operative ECMO were excluded. CS-AKI was defined using the modified neonatal Kidney Disease: Improving Global Outcomes serum creatinine or urine output (UOP) criteria. UOP criteria were only used in the presence of an indwelling bladder catheter. Transient CS-AKI was defined as resolved by POD 3, and persistent CS-AKI as still present on/after POD 3. Severe CS-AKI was stage 2 or 3. Results: Three-hundred for ty-six patients were included. Of 211 (61.0%) with CS-AKI, 127 (36.7%) were transient, 29 (8.4%) severe transient, 78 persistent (22.5%) and 23 (6.6%) severe persistent. Only 5 (1.4%) had delayed onset CS-AKI and were not included in comparative analysis. On univariate analysis, patients that developed persistent CS-AKI had lower intensive care unit admit systolic blood pressure, higher vasoactive inotrope score, higher % fluid overload on POD 0, 1, and more major post-op complications. Of the 15% who underwent prophylactic peritoneal dialysis, 30/51 (58.9%) had transient and 10/51 (19.6%) had persistent CS-AKI. Transient and persistent CS-AKI occurred less frequently in patients exposed to preoperative feeds (Table 1A). Patients with persistent CS-AKI had 3.5 times higher mortality than no AKI. However, on multivariable analysis, persistent CS-AKI was not statistically associated with mortality, respiratory support free days at 28 days and hospital free days at 60 days (Table 1B).   Understanding which neonates would benefit from prophylactic PD is needed to optimize care. We sought to: 1) determine which neonates would most benefit from prophylactic PD after CPB based on patient-specific characteristics via retrospective analysis; 2) implement a new prophylactic PD protocol based on our retrospective analysis; and 3) determine the effectiveness of our new protocol. Methods: First, we retrospectively evaluated neonates requiring cardiac surgery with CPB from October 2012 through June 2016. We categorized neonates as those who "needed PD" and those who "did not need PD." We defined "needed PD" as those who had a PD catheter placed in the OR that was used for >48 hours, or those who did not have a PD catheter placed in the OR but in retrospect would have benefited from PD based on predetermined clinical findings. Of the variables examined, only pre-operative serum creatinine ≥ 0.8 mg/dL, pre-operative weight ≤ 2.5 kg, or having an open chest postoperatively were independently associated with "needed PD." Next, beginning March 2019 we implemented a new prophylactic PD protocol so that only those who met at least one of the three criteria had a PD catheter placed in the OR. Finally, we analyzed the second era experience.

Results:
In the first era, of the 67 neonates in the "needed PD" group, 9/67 (13.4%) did not have a PD catheter placed in the OR while of the 81 neonates in the "did not need PD" group, 41/81 (50.6%) had a PD catheter placed. Alternatively, in the second era, of the 28 neonates in the "needed PD" group, 0/28 (0%) did not have a PD catheter placed in the OR while of the 69 neonates in the "did not need PD" group, 18/69 (26.1%) had a PD catheter placed. Conclusion: We successfully developed and implemented an evidence-based prophylactic PD protocol. This risk-based protocol has improved our ability to provide prophylactic PD in neonates requiring CPB. Larger prospective studies are needed to further validate our findings.     Background: AKI contributes significantly to short and long-term outcomes following critical illness in children.
More than a quarter of pediatric intensive care unit (PICU) patients experience AKI. The initial insult of AKI in PICU patients may predispose them to recurrence in future hospitalizations but literature is limited on this potential association. Our study aimed to explore this potential association and possible risk factors for subsequent kidney injury. Methods: A retrospective, single-center, observational study was conducted comparing patients with AKI during first admission to the PICU to a control group without AKI on first admission. The study included patients less than 19 years old on initial admission between January 1, 2014 to December 31, 2020. Patients with pre-existing kidney disease, death during first admit, or no readmissions were excluded. Kidney Disease Improving Global Outcomes criteria were used for staging of AKI. Pediatric Risk of Mortality (PRISM) scores classified severity of illness and Nephrotoxic Injury Negated by Just in time Action (NINJA) criteria were used to define nephrotoxic drug exposure. 1 There were 91 study patients and 94 age-matched controls. Analyses of quantitative and qualitative data were done by t-test and chi-squared test respectively. Results: There was a significant association between AKI during the initial PICU stay and future recurrence(s) of AKI (p <.0001) (see Table 1 for details). The AKI positive group were more likely to develop chronic kidney disease (CKD) (p <.0001). This group had a higher proportion of cardiovascular disease (p <.0001) and higher PRISM scores (p <.0001).  Background: Fluid overload remains associated with worse outcomes in critically ill patients. This impact is exacerbated in low resource areas with limited dialysis access. A single lumen alternating micro-batch (SLAMB) dialysis device performs ultrafiltration and renal replacement therapy (RRT) using single lumen access, a low-cost set of bags and tubing, premade fluids, and a dialysis filter. A manual variation of the SLAMB (mSLAMB) has been shown to work without the use of electricity, batteries, or a pump. We hypothesize that mSLAMB can perform effective ultrafiltration via progressive manual fluid removal. Methods: Four in vitro experiments were conducted wherein expired human packed red blood cells were diluted with 0.9% saline to a hematocrit of 20± 3%. mSLAMB was connected to a polyflux 6H filter, but no dialysate/hemofiltration fluids were utilized. In each cycle, 200mL batches were run forward and reverse through the filter. Different percentages of batch volume were removed with a syringe: 20% on reverse pass only, 15% per pass, and 20% per pass. Eight to 11 cycles were conducted per experiment, and the total fluid removed, hematocrit, and potassium were measured. Results: We removed 40-80 mL of fluid via active manual ultrafiltration per cycle, and 0-20 mL per cycle of passive ultrafiltration occurred as well. There was a generally linear relationship between the increase in cumulative ultrafiltration and hematocrit, as evidence by a slow rise in hematocrit with each cycle (Figure 1). The hematocrit difference after 10 cycles was 2.4%, 9%, 10.5%, and 13.5% (the latter after only 8 cycles) with 20%, 30%, 30%, and 40% batch volume removed. Actual hematocrits obtained with 30% batch volume removal closely mirrored predicted hematocrit rise with each cycle. In the last few years, other institutions have begun developing their own programs and our team was contacted with questions rather frequently. We put together a course to share our knowledge about kidney support therapy and named it the Neonatal and Infant Course for Kidney Support (NICKS). We debuted virtually in July 2020. Using didactic sessions, hands-on skills sessions and simulations over one and a half days, the overarching goal for NICKS is to help programs acquire the knowledge and skills to be successful.

Methods:
We have held eight courses since July 2020. We have hosted 340 participants from 90 cities in 14 countries and 32 US states. Of those participants, 35% were nurses, 10% were advanced practice providers and 55% were physicians, with 49% specializing in nephrology, 30% in neonatology and 21% in intensive care. We assessed comfortability with initiating KST on a 4kg, 2kg, and 1kg baby. 283 participants responded to our pretest and 276 participants responded to our posttests.

Results:
The results of the pretest and posttest confirm that our participants are more comfortable with starting babies on continuous kidney support therapy after attending our course.

Conclusions:
The NICKS course has provided education for 340 participants using a multidisciplinary approach. The level of comfort for caring for neonates increases after the course. We plan to continue this course in the future.   Background: Neonates born with congenital kidney failure can have severe pulmonary hypoplasia and pulmonary hypertension. Historically, extracorporeal membrane oxygenation (ECMO) has been avoided in patients with congenital kidney failure and associated pulmonary hypoplasia due to concerns regarding irreversibility. Since 2016, 31 neonates have been admitted to the Neonatal Intensive Care Unit at Children's of Alabama with congenital kidney failure and pulmonary hypoplasia requiring kidney support therapy. Four of these patients were placed on ECMO for pulmonary hypoplasia/hypertension unresponsive to conventional interventions in the first postnatal week. The primary aim of this case series is to describe the clinical courses and long-term outcomes in this unique patient group. Methods: This case series highlights the clinical courses of four neonates with congenital kidney failure, severe pulmonary hypoplasia/hypertension refractory to conventional therapies who were supported with ECMO. Pre and postnatal diagnoses, ECMO course details, kidney support therapy methods, complications, procedures, and long-term outcomes were evaluated. Results: Of the four patients, one was diagnosed with posterior urethral valves (PUV), one with bilateral renal dysplasia, and two with autosomal recessive polycystic kidney disease (ARPKD). Gestational age ranged from 35 weeks 6 days to 37 weeks 6 days. Birth weight range was 2740 grams to 3140 grams. Total days on ECMO ranged from 4 to 23 days. All patients received kidney support therapy by one week of life. Comorbidities and long-term outcomes are detailed in the full case study. All survived to discharge and are still living today. Pulmonary hypertension has resolved in all patients. Two of the four require no oxygen support, and the younger two patients are on nocturnal oxygen only. Two of these patients have received a kidney transplant, one patient remains on the waiting list for transplant, and one patient is awaiting transplant evaluation. Conclusions: Patients with congenital kidney failure with pulmonary hypoplasia and severe pulmonary hypertension are compatible with life, even if they require organ support with ECMO. The multidisciplinary team that can work together to provide respiratory, kidney and comprehensive medical support is necessary to have favorable long-term outcomes. Further investigation into strategies to achieve best outcomes is needed. Keywords: extracorporeal membrane oxygenation (ECMO), kidney support therapy (KST), pulmonary hypertension, pulmonary hypoplasia, outcomes Disclosures: D. Askenazi is consultant and/or receives education/research funds from Baxter, Nuwellis, Medtronic, Seastar, Bioporto, Portero. He is the CSO and founder of Zorro-Flow Inc. D. Ingram is a consultant for Nuwellis. Odds ratio (OR) and 95% confidence interval (CI) obtained by multivariable logistic regression model for mortality.