Search

Acute kidney injury (AKI) occurs in one-fourth of children and young adults admitted to pediatric intensive care unit (PICU). Severe AKI (sAKI; Kidney Disease: Improving Global Outcomes stage 2 or 3) is associated with morbidity and mortality. An AKI risk stratification system, the Renal Angina Index (RAI) calculated at 12 hours of admission, exhibits excellent performance to rule out sAKI at 72 hours of admission. We found that integration of urine neutrophil gelatinase-associated lipocalin (NGAL) with RAI improves prediction of sAKI. We now report the first-year results after implementation of our prospective automated RAI-NGAL clinical decision support (CDS) program.Patients 3 months to 25 years of age were eligible. Admission order sets have a conditional order for urine NGAL released when a 12-hour RAI ≥8. The primary outcome was sAKI any time at days 2 to 4 of admission. We assessed performance of the RAI and RAI+/NGAL to predict the primary outcome.A total of 1427 unique patients accounted for 1575 admissions. In 147 admissions, RAI was ≥8. RAI 8 had negative predictive value (NPV) of 0.98 (95% CI 0.97-0.99); RAI ≥ 8 had positive predictive value (PPV) of 0.37 (95% CI 0.30-0.46) to predict days 2 to 4 sAKI (area under the receiver operating characteristic curve [AUC-ROC] 0.88 [95% CI 0.84-0.92]). Of 147 RAI+ patients, 89 had NGAL available. RAI/NGAL combination improved PPV (0.64, 95% CI 0.50-0.79) without decrement in NPV (0.98, 95% CI 0.97-0.98).AKI biomarker assessment directed by risk stratification improves prediction of sAKI in critically ill children and young adults. This CDS process has potential to enrich the population for interventional study, although improvement to adherence to CDS is needed.

Background:Reliable prediction of severe acute kidney injury (AKI) and related poor outcomes has the potential to optimize treatment. The purpose of this study was to modify the renal angina index in pediatric cardiac surgery to predict severe AKI and related poor outcomes. Methods: We performed a multicenter retrospective study with the population divided into a derivation and validation cohort to assess the performance of a modified renal angina index assessed at 8 h after cardiac intensive care unit (CICU) admission to predict a complex outcome of severe day 3 AKI or related poor outcomes (ventilation duration >7 days, CICU length of stay >14 days, and mortality). The derivation sample was used to determine the optimal cut-off value. Results: There were 298 and 299 patients in the derivation and validation cohorts, respectively. The incidence of severe day 3 AKI and the complex outcome was 1.7% and 28% in the derivation and validation cohort. The sensitivity analysis for fulfillment of renal angina was a score >8 with a sensitivity of 63%, specificity of 73%, and negative predictive value of 83%. The cardiac renal angina index predicted the composite outcome with an area under the curve of 0.7 (95% confidence interval: 0.62-0.78). Renal angina patients had a significantly higher probability of the complex outcome when compared to individual risk and injury categories. Conclusions: We operationalized the renal angina index for use after cardiac surgery. Further revision and modification of the construct with integration of biomarkers in a prospective cohort are necessary to refine the prediction model.

Intravenous (IV) fluids are commonly administered to critically ill children, but clinicians lack effective guidance for the correct dose and duration of therapy resulting in variation of prescribing habits which harm children. It is unknown if clinicians recognize the amount of IV fluid that patients receive. We aimed to determine clinician's accuracy in the identification of the volume of IV fluids patients will receive over the next 24 hours. Prospective cohort study enrolled all patients admitted to the pediatric intensive care unit (PICU) from May to August 2021 at the University of Michigan's C.S. Mott Children's Hospital PICU. For each patient, clinicians estimated the volume of IV fluid that patients will receive in the next 24 hours. The primary outcome was accuracy of the estimation defined as predicted volume of IV fluids versus actual volume administered within 10 mL/kg or 500 mL depending on patient's weight. We tested for differences in accuracy by clinician type using chi-square tests. There were 259 patients for whom 2,295 surveys were completed by 177 clinicians. Clinicians' estimates were accurate 48.8% of the time with a median difference of 10 (1–26) mL/kg. We found that accuracy varied between clinician type: bedside nurses were most accurate at 64.3%, and attendings were least accurate at 30.5%. PICU clinicians have poor recognition of the amount of IV fluids their patients will receive in the subsequent 24-hour period. Estimate accuracy varied by clinician's role and improved over time, which may suggest opportunities for improvement.

ImportanceIncreasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge.ObjectiveTo develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy.Evidence ReviewAt the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations.FindingsThe meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy.Conclusions and RelevanceExisting evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.

Very little data is available to understand the drivers of burnout amongst health care workers in the pediatric intensive care unit. This is a survey-based, cross-sectional, point-prevalence analysis within a single children's health system with two free-standing hospitals (one academic and one private) to characterize the relationship of demographics, organizational support, organizational culture, relationship quality, conflict and work schedules with self-reported burnout. Burnout was identified in 152 (39.7%) of the 383 (38.7%) respondents. No significant relationship was identified between burnout and demographic factors or work schedule. A more constructive culture (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.77–0.90; p

Acute kidney injury (AKI), fluid overload (FO), and mortality are common in pediatric patients supported by extracorporeal membrane oxygenation (ECMO). The aim of this study is to evaluate if using a fluid management algorithm reduced AKI and mortality in children supported by ECMO. We performed a retrospective study of pediatric patients aged birth to 25 years requiring ECMO at a quaternary level children's hospital from 2007 to 2019 In October 2017, a fluid management algorithm was implemented for protocolized fluid removal after deriving a daily fluid goal using a combination of diuretics and ultrafiltration. Daily algorithm compliance was defined as ≥ 12 h on the algorithm each day. The primary and secondary outcomes were AKI and mortality, respectively, and were assessed in the entire cohort and the sub-analysis of children from the era in which the algorithm was implemented. Two hundred and ninety-nine (median age 5.3 months; IQR: 0.2, 62.3; 45% male) children required ECMO (venoarterial in 85%). The fluid algorithm was applied in 74 patients. The overall AKI rate during ECMO was 38% (26% severe-stage 2/3). Both AKI incidence and mortality were significantly lower in patients managed on the algorithm (p = 0.02 and p = 0.05). After adjusting for confounders, utilization of the algorithm was associated with lower odds of AKI (aOR: 0.40, 95%CI: 0.21, 0.76; p = 0.005) but was not associated with a reduction in mortality. In the sub-analysis, algorithm compliance of 80-100% was associated with a 54% reduction in mortality (ref: 60% compliant; aOR:0.46, 95%CI:0.22-1.00; p = 0.05). Conclusion: Among the entire cohort, the use of a fluid management algorithm reduced the odds of AKI. Better compliance on the algorithm was associated with lower mortality. Multicenter studies that implement systematic fluid removal may represent an opportunity for improving ECMO-related outcomes. What is Known: • Acute kidney injury and fluid overload are associated with morbidity and mortality in children supported by extracorporeal membrane oxygenation. What is New: • A systematic and protocolized approach to fluid removal in children supported by extracorporeal membrane oxygenation reduces acute kidney injury incidence. • Greater adherence to a protocolized fluid removal algorithm is associated with a reduction in mortality.

Introduction Sepsis-associated acute kidney injury (AKI) is a common diagnosis in children that is associated with poor outcomes. The lack of therapeutic options once present makes early identification of at-risk patients essential. The renal angina index (RAI) has been previously validated to predict severe AKI in heterogeneous populations of critically ill children. The performance of this score specifically in children with septic shock is unknown. Methods A secondary analysis of a multicenter, prospective, observational study of 379 children with septic shock to determine the ability of the RAI to predict severe AKI at day 3, and to assess for the potential need for recalibration of the RAI in this unique subset of patients. Results At the original cutoff of ≥8, the RAI predicted day 3 severe AKI with an area under the receiving operating characteristic (AUROC) curve 0.90 (95% confidence interval [CI]: 0.86 to 93), 95% sensitivity, and 54% specificity. A Youden’s index identified a higher optimal cutoff of ≥20 (sensitivity 83%, specificity 80%), and day 1 platelet count, Graphical abstract

Introduction Critically ill children with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT) are at increased risk of death. The selective cytopheretic device (SCD) promotes an immunomodulatory effect when circuit ionized calcium (iCa2+) is maintained at, Graphical abstract

Background Large volumes of non-resuscitation fluids are often administered to critically ill children. We hypothesize that excess maintenance fluid is a significant contributor to non-resuscitation fluid and that non-resuscitation fluid administered beyond hydration requirements is associated with worse clinical outcomes in critically ill children. Methods We evaluated all patients admitted to two large urban pediatric intensive care units (PICU) between January 2010-August 2016 and January 2010-August 2018, respectively, who survived and remained in the hospital for at least 3 days following PICU admission. The primary outcome was in-hospital mortality. Association of excess fluid with outcomes was adjusted for confounders (age, Pediatric Risk of Mortality III score, study site, day 3 acute kidney injury, PICU era, resuscitation volume, and volume output) using multivariable regression. Results We evaluated 14,483 patients; 52% received non-resuscitation fluid in excess of hydration requirements. Non-resuscitation fluid in excess of hydration requirements was associated with higher in-hospital mortality after adjustment for confounders (adjusted odds ratio 1.01 per 10 mL/kg in excess fluid, 95% confidence interval: 1.002-1.02). Conclusions Non-resuscitation fluid in excess of hydration requirements is associated with increased mortality in critically ill children. Excess maintenance fluid is a modifiable contributor to this fluid volume. Strategies to reduce excess maintenance fluids warrant further study. Impact Critically ill children frequently receive non-resuscitation fluid in excess of their estimated hydration requirements. Non-resuscitation fluid volume in excess of estimated hydration requirements is associated with higher morbidity and mortality in critically ill children. Critically ill children receive a large volume burden from maintenance fluid. Maintenance fluid represents a modifiable contributor of non-resuscitation fluid in excess of hydration requirements. Strategies focused on limitation of maintenance fluid warrant further study.

BACKGROUND Assessment of acute kidney injury (AKI) in septic patients remains imprecise. In adults, the classification of septic patients by clinical AKI phenotypes (severity and timing) demonstrates unique associations with patient outcome vs. broadly defined AKI. METHODS In a multinational prospective observational study, AKI diagnosis in critically ill septic children was stratified by duration (transient vs. persistent) and severity (mild vs. severe by creatinine change and urine output). The outcomes of interest were mortality and intensive care unit resource complexity at 28 days. RESULTS Seven hundred and fifty-seven septic children were studied (male 52.7%, age 4.6 years (1.5-11.9)). Mortality (overall 12.1%) was different between severe AKI and mild AKI (18.3 vs. 4.4%, p

Introduction: We aimed to characterize acute kidney injury (AKI), fluid overload (FO), and renal replacement therapy (RRT) utilization by diagnostic categories and examine associations between these complications and mortality by category. Methods: To test our hypotheses, we conducted a retrospective multicenter, cohort study including 446 neonates (categories: 209 with cardiac disease, 114 with congenital diaphragmatic hernia [CDH], 123 with respiratory disease) requiring extracorporeal membrane oxygenation (ECMO) between January 1, 2007, and December 31, 2011. Results: AKI, FO, and RRT each varied by diagnostic category. AKI and RRT receipt were most common in those neonates with cardiac disease. Subjects with CDH had highest peak %FO (51% vs. 28% cardiac vs. 32% respiratory; p < 0.01). Hospital survival was 55% and varied by diagnostic category (45% cardiac vs. 48% CDH vs. 79% respiratory; p < 0.001). A significant interaction suggested risk of mortality differed by diagnostic category in the presence or absence of AKI. In its absence, diagnosis of CDH (vs. respiratory disease) (OR 3.04, 95% CL 1.14–8.11) independently predicted mortality. In all categories, peak %FO (OR 1.20, 95% CL 1.11–1.30) and RRT receipt (OR 2.12, 95% CL 1.20–3.73) were independently associated with mortality. Discussion/Conclusions: Physiologically distinct ECMO diagnoses warrant individualized treatment strategies given variable incidence and effects of AKI, FO, and RRT by category on mortality.

With the adoption of standardized neonatal acute kidney injury (AKI) definitions over the past decade and the concomitant surge in research studies, the epidemiology of and risk factors for neonatal AKI have become much better understood. Thus, there is now a need to focus on strategies designed to improve AKI care processes with the goal of reducing the morbidity and mortality associated with neonatal AKI. The 22nd Acute Dialysis/Disease Quality Improvement (ADQI) report provides a framework for such quality improvement in adults at risk for AKI and its sequelae. While many of the concepts can be translated to neonates, there are a number of specific nuances which differ in neonatal AKI care. A group of experts in pediatric nephrology and neonatology came together to provide neonatal-specific responses to each of the 22nd ADQI consensus statements.

OBJECTIVES Evaluate the independent and synergistic associations of fluid overload and acute kidney injury with outcome in critically ill pediatric patients. DESIGN Secondary analysis of the Acute Kidney Injury in Children Expected by Renal Angina and Urinary Biomarkers (NCT01735162) prospective observational study. SETTING Single-center quaternary level PICU. PATIENTS One-hundred forty-nine children 3 months to 25 years old with predicted PICU length of stay greater than 48 hours, and an indwelling urinary catheter enrolled (September 2012 to March 2014). Acute kidney injury (defined by creatinine or urine output on day 3) and fluid overload (≥ 20% on day 3) were used as outcome variables and risk factors for ICU endpoints assessed at 28 days. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Acute kidney injury and fluid overload occurred in 19.4% and 24.2% respectively. Both acute kidney injury and fluid overload were associated with longer ICU length of stay but neither maintained significance after multivariate regression. Delineation into unique fluid overload/acute kidney injury classifications demonstrated that fluid overload patients experienced a longer ICU and hospital length of stay and higher rate of mortality compared with fluid overload patients, regardless of acute kidney injury status. Fluid overload/acute kidney injury patients had increased odds of death (p = 0.013). After correction for severity of illness, ICU length of stay remained significantly longer in fluid overload/acute kidney injury patients compared with patients without both classifications (17.4; 95% CI, 11.0-23.7 vs 8.8; 95% CI, 7.3-10.9; p = 0.05). Correction of acute kidney injury classification for net fluid balance led to acute kidney injury class switching in 29 patients and strengthened the association with increased mechanical ventilation and ICU length of stay on bivariate analysis, but reduced the increased risk conferred by fluid overload for mortality. CONCLUSIONS The current study suggests the effects of significant fluid accumulation may be delineable from the effects of acute kidney injury. Concurrent fluid overload and acute kidney injury significantly worsen outcome. Correction of acute kidney injury assessment for net fluid balance may refine diagnosis and unmask acute kidney injury associated with deleterious downstream sequelae. The unique effects of fluid overload and acute kidney injury on outcome in critically ill patients warrant further study.

CONTEXT Renal dysfunction is associated with poor outcomes in critically ill children. OBJECTIVE To evaluate the current evidence for criteria defining renal dysfunction in critically ill children and association with adverse outcomes. To develop contemporary consensus criteria for renal dysfunction in critically ill children. DATA SOURCES PubMed and Embase were searched from January 1992 to January 2020. STUDY SELECTION Included studies evaluated critically ill children with renal dysfunction, performance characteristics of assessment tools for renal dysfunction, and outcomes related to mortality, functional status, or organ-specific or other patient-centered outcomes. Studies with adults or premature infants (≤36 weeks' gestational age), animal studies, reviews, case series, and studies not published in English with inability to determine eligibility criteria were excluded. DATA EXTRACTION Data were extracted from included studies into a standard data extraction form by task force members. RESULTS The systematic review supported the following criteria for renal dysfunction: (1) urine output LIMITATIONS All included studies were observational and many were retrospective. CONCLUSIONS We present consensus criteria for renal dysfunction in critically ill children.

Acute kidney injury (AKI) and fluid overload (FO) are common complications of extracorporeal membrane oxygenation (ECMO). The purpose of this study was to characterize AKI and FO in children receiving extracorporeal cardiopulmonary resuscitation (eCPR). We performed a multicenter retrospective study of children who received eCPR. AKI was assessed during ECMO and FO defined as

Hematopoietic cell transplantation (HCT) is a common therapy for the treatment of neoplastic and metabolic disorders, hematological diseases, and fatal immunological deficiencies. HCT can be subcategorized as autologous or allogeneic, with each modality being associated with their own benefits, risks, and post-transplant complications. One of the most common complications includes acute kidney injury (AKI). However, diagnosing HCT patients with AKI early on remains quite difficult. Therefore, this evidence-based guideline, compiled by the Pediatric Continuous Renal Replacement Therapy (PCRRT) working group, presents the various factors that contribute to AKI and recommendations regarding optimization of therapy with minimal complications in HCT patients.

BACKGROUND AND OBJECTIVES: AKI is a common complication after pediatric cardiac surgery and has been associated with higher morbidity and mortality. We aimed to compare the efficacy of available pharmacologic and nonpharmacologic strategies to prevent AKI after pediatric cardiac surgery. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: PubMed/MEDLINE, Embase, Cochrane Controlled Trials Register, and reference lists of relevant articles were searched for randomized controlled trials from inception until August 2020. Random effects traditional pairwise, Bayesian network meta-analyses, and trial sequential analyses were performed. RESULTS: Twenty randomized controlled trials including 2339 patients and 11 preventive strategies met the eligibility criteria. No overall significant differences were observed compared with control for corticosteroids, fenoldopam, hydroxyethyl starch, or remote ischemic preconditioning in traditional pairwise meta-analysis. In contrast, trial sequential analysis suggested a 80% relative risk reduction with dexmedetomidine and evidence of

PURPOSE OF REVIEW Paediatric patients represent a unique challenge for providers managing acute kidney injury (AKI). Critical care for these children requires a precise approach to assessment, diagnostics and management. RECENT FINDINGS Primarily based on observational data, large epidemiologic datasets have demonstrated a strong association between AKI prevalence (one in four critically ill children) and poor patient outcome. Drivers of AKI itself are multifactorial and the causal links between AKI and host injury remain incompletely defined, creating a management paradigm primarily supportive in nature. The previous decades of research have focused primarily on elucidating the population-level epidemiologic signal of AKI and use of renal replacement therapy (RRT), but in order to reverse the course of the AKI 'epidemic', future decades will require more attention to the individual patient. A patient-level approach to AKI in children will require sophisticated approaches to risk stratification, diagnostics and targeted utilization of therapies (both supportive and targeted towards drivers of injury). SUMMARY In this review, we will summarize the past, present and future of AKI care in children, discussing the ongoing work and future goals of a personalized approach to AKI medicine.

Objective: Predict the onset of presumed serious infection, defined as a positive blood culture drawn and new antibiotic course of at least 4 days (PSI*), among pediatric patients with Central Venous Lines (CVLs).Design: Retrospective cohort study.Setting: Single academic children's hospital.Patients: All hospital encounters from January 2013 to December 2018, excluding the ones without a CVL or with a length-of-stay shorter than 24 h.Measurements and Main Results: Clinical features including demographics, laboratory results, vital signs, characteristics of the CVLs and medications used were extracted retrospectively from electronic medical records. Data were aggregated across all hospitals within a single pediatric health system and used to train a deep learning model to predict the occurrence of PSI* during the next 48 h of hospitalization. The proposed model prediction was compared to prediction of PSI* by a marker of illness severity (PELOD-2). The baseline prevalence of line infections was 0.34% over all segmented 48-h time windows. Events were identified among cases using onset time. All data from admission till the onset was used for cases and among controls we used all data from admission till discharge. The benchmarks were aggregated over all 48 h time windows [N=748,380 associated with 27,137 patient encounters]. The model achieved an area under the receiver operating characteristic curve of 0.993 (95% CI = [0.990, 0.996]), the enriched positive predictive value (PPV) was 23 times greater than the base prevalence. Conversely, prediction by PELOD-2 achieved a lower PPV of 1.5% [0.9%, 2.1%] which was 5 times the baseline prevalence.Conclusion: A deep learning model that employs common clinical features in the electronic health record can help predict the onset of CLABSI in hospitalized children with central venous line 48 hours prior to the time of specimen collection.

A standardized, quantified assessment of furosemide responsiveness predicts acute kidney injury (AKI) in children after cardiac surgery and AKI progression in critically ill adults. The purpose of this study was to determine if response to furosemide is predictive of severe AKI in critically ill children outside of cardiac surgery. We performed a multicenter retrospective study of critically ill children. Quantification of furosemide response was based on urine flow rate (normalized for weight) measurement 0 to 6 hours after the dose. The primary outcome was presence of creatinine defined severe AKI (Kidney Disease Improving Global Outcomes stage 2 or greater) within 7 days of furosemide administration. Secondary outcomes included mortality, duration of mechanical ventilation and length of stay. A total of 110 patients were analyzed. Severe AKI occurred in 20% (n = 22). Both 2- and 6-hour urine flow rate were significantly lower in those with severe AKI compared with no AKI (p = 0.002 and p

Background:Acute kidney injury is a common complication following the Norwood operation. Most neonatal studies report acute kidney injury peaking within the first 48 hours after cardiac surgery. The aim of this study was to evaluate if persistent acute kidney injury (>48 postoperative hours) after the Norwood operation was associated with clinically relevant outcomes.Methods:Two-centre retrospective study among neonates undergoing the Norwood operation. Acute kidney injury was initially identified as developing within the first 48 hours after cardiac surgery and stratified into transient (≤48 hours) and persistent (>48 hours) using the neonatal modification of the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Severe was defined as stage ≥2. Primary and secondary outcomes were mortality and duration of ventilation and hospital length of stay.Results:One hundred sixty-eight patients were included. Transient and persistent acute kidney injuries occurred in 24 and 17%, respectively. Cardiopulmonary bypass and aortic cross clamp duration, and incidence of cardiac arrest were greater among those with persistent kidney injury. Mortality was four times higher (41 versus 12%, p < 0.001) and mechanical ventilation duration 50 hours longer in persistent acute kidney injury patients (158 versus 107 hours; p < 0.001). In multivariable analysis, persistent acute kidney injury was not associated with mortality, duration of ventilation or length of stay. Severe persistent acute kidney injury was associated with a 59% increase in expected ventilation duration (aIRR:1.59, 95% CI:1.16, 2.18; p = 0.004).Conclusions:Future large studies are needed to determine if risk factors and outcomes change by delineating acute kidney injury into discrete timing phenotypes.

Low plasma arginine bioavailability has been implicated in endothelial dysfunction and immune dysregulation. The role of arginine in COVID-19 is unknown, but could contribute to cellular damage if low. Our objective was to determine arginine bioavailability in adults and children with COVID-19 vs. healthy controls. We hypothesized that arginine bioavailability would be low in patients with COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We conducted a prospective observational study of three patient cohorts; arginine bioavailability was determined in asymptomatic healthy controls, adults hospitalized with COVID-19, and hospitalized children/adolescents t test. Arginine-to-ornithine ratio, a biomarker of arginase activity, and global arginine bioavailability ratio (GABR, arginine/[ornithine+citrulline]) were assessed in all three groups. A total of 80 patients were included (28 controls, 32 adults with COVID-19, and 20 pediatric patients with COVID-19/MIS-C). Mean plasma arginine and arginine bioavailability ratios were lower among adult and pediatric patients with COVID-19/MIS-C compared to controls. There was no difference between arginine bioavailability in children with COVID-19 vs. MIS-C. Adults and children with COVID-19 and MIS-C in our cohort had low arginine bioavailability compared to healthy adult controls. This may contribute to immune dysregulation and endothelial dysfunction in COVID-19. Low arginine-to-ornithine ratio in patients with COVID-19 or MIS-C suggests an elevation of arginase activity. Further study is merited to explore the role of arginine dysregulation in COVID-19.

Background Increasing AKI diagnosis precision to refine the understanding of associated epidemiology and outcomes is a focus of recent critical care nephrology research. Timing of onset of acute kidney injury (AKI) during pediatric critical illness and impact on outcomes has not been fully explored. Methods This was a secondary analysis of the Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology (AWARE) database. AKI was defined as per Kidney Disease: Improving Global Outcomes criteria. Early AKI was defined as diagnosed at ≤48 h after intensive care unit (ICU) admission, with any diagnosis >48 h denoted as late AKI. Transient AKI was defined as return to baseline serum creatinine ≤48 h of onset, and those without recovery fell into the persistent category. A second incidence of AKI ≥48 h after recovery was denoted as recurrent. Patients were subsequently sorted into distinct phenotypes as early-transient, late-transient, early-persistent, late-persistent and recurrent. Primary outcome was major adverse kidney events (MAKE) at 28 days (MAKE28) or at study exit, with secondary outcomes including AKI-free days, ICU length of stay and inpatient renal replacement therapy. Results A total of 1262 patients had AKI and were included. Overall mortality rate was 6.4% (n = 81), with 34.2% (n = 432) fulfilling at least one MAKE28 criteria. The majority of patients fell in the early-transient cohort (n = 704, 55.8%). The early-persistent phenotype had the highest odds of MAKE28 (odds ratio 7.84, 95% confidence interval 5.45–11.3), and the highest mortality rate (18.8%). Oncologic and nephrologic/urologic comorbidities at AKI diagnosis were associated with MAKE28. Conclusion Temporal nature and trajectory of AKI during a critical care course are significantly associated with patient outcomes, with several subtypes at higher risk for poorer outcomes. Stratification of pediatric critical care-associated AKI into distinct phenotypes is possible and may become an important prognostic tool.

Olivia, a 13-year-old neurologically intact patient with cerebral palsy, arrived from a routine abdominal procedure screaming in pain. The medical team was baffled as to why she experienced such agony despite receiving copious doses of morphine. We spoke with her adoptive parents to obtain more history. They revealed long-standing physical and sexual abuse before Olivia’s adoption 6 years ago and noted extreme distress to all medical procedures and prolonged surgical healing time. Although her parents hoped to give her a better life and ensure she received appropriate care for her condition, they felt helpless that Olivia was at risk for retraumatization (reexperiencing posttraumatic symptoms from her original traumas) each time she came to the hospital. The amplification of pain and delayed medical recovery secondary to a history of psychological trauma and adverse childhood experiences (ACEs) is well recognized.1–3 Health care institutions are aware of the need for the integration of trauma-informed care into practice, yet they struggle to find the right approach. Although screening for ACEs has been widely adopted as a trauma-informed practice, there are multiple concerns with ACEs screening, including operating from a deficit- versus strength-based model, risk for traumatization from screening, and limited follow-up resources.4 ACEs scores also do not fully capture trauma and posttraumatic stress symptoms, which may be better predictors of negative outcomes than ACEs alone. Many organizations have now implemented the Substance Abuse and Mental Health Services Administration guidelines of educating clinicians on realizing …

Purpose Acute kidney injury (AKI) is prevalent in critically ill patients and associated with poor outcomes. Current AKI diagnostics— changes to serum creatinine (SCr) and urine output— are imprecise. Integration of injury biomarkers with SCr may improve diagnostic precision. Methods We performed a secondary analysis of a study of critically ill children. Measurements of urine neutrophil gelatinase-associated lipocalin (uNGAL) and SCr samples from ICU admission facilitated the creation of four groups for comparison, based on elevation of SCr from baseline and reference NGAL cut-off value: uNGAL-/SCr-, uNGAL+/SCr-, uNGAL-/SCr + and uNGAL+/SCr+. The primary outcome assessed was AKI severity on Day 3. Results 178 children were studied. Compared to uNGAL-/SCr-, uNGAL+/SCr- patients had increased risk for all-stage Day 3 AKI (≥ KDIGO stage 1) (OR 3.83, [1.3–11.3], p = .025). Compared to uNGAL-/SCr+, uNGAL+/SCr + patients had increased risk for severe Day 3 AKI (≥ KDIGO stage 2) (OR 12, [1.4–102], p = .018). The only patients to suffer all-stage Day 3 AKI and mortality were uNGAL+ (3.2% uNGAL+/SCr-; 6.5% uNGAL+/SCr+). Conclusions Unique biomarker combinations on admission are predictive of distinct Day 3 AKI severity phenotypes. These classifications may enable a more personalized approach to the early management of AKI. Expanded study in larger populations is warranted.

PURPOSE OF REVIEW: Acute kidney injury (AKI) and fluid overload affect a large number of children undergoing cardiac surgery, and confers an increased risk for adverse complications and outcomes including death. Survivors of AKI suffer long-term sequelae. The purpose of this narrative review is to discuss the short and long-term impact of cardiac surgery associated AKI and fluid overload, currently available tools for diagnosis and risk stratification, existing management strategies, and future management considerations. RECENT FINDINGS: Improved risk stratification, diagnostic prediction tools and clinically available early markers of tubular injury have the ability to improve AKI-associated outcomes. One of the major challenges in diagnosing AKI is the diagnostic imprecision in serum creatinine, which is impacted by a variety of factors unrelated to renal disease. In addition, many of the pharmacologic interventions for either AKI prevention or treatment have failed to show any benefit, while peritoneal dialysis catheters, either for passive drainage or prophylactic dialysis may be able to mitigate the detrimental effects of fluid overload. SUMMARY: Until novel risk stratification and diagnostics tools are integrated into routine practice, supportive care will continue to be the mainstay of therapy for those affected by AKI and fluid overload after pediatric cardiac surgery. A viable series of preventative measures can be taken to mitigate the risk and severity of AKI and fluid overload following cardiac surgery, and improve care.

Intentional or unintentional ingestions among children and adolescents are common. There are a number of ingestions amenable to renal replacement therapy (RRT). We systematically searched PubMed/Medline, Embase, and Cochrane databases for literature regarding drugs/intoxicants and treatment with RRT in pediatric populations. Two experts from the PCRRT (Pediatric Continuous Renal Replacement Therapy) workgroup assessed titles, abstracts, and full-text articles for extraction of data. The data from the literature search was shared with the PCRRT workgroup and two expert toxicologists, and expert panel recommendations were developed. We have presented the recommendations concerning the use of RRTs for treatment of intoxications with toxic alcohols, lithium, vancomycin, theophylline, barbiturates, metformin, carbamazepine, methotrexate, phenytoin, acetaminophen, salicylates, valproic acid, and aminoglycosides.

BACKGROUND: The Renal Angina Index (RAI) is a validated screening tool used at 12 h of pediatric intensive care unit (PICU) admission to predict severe acute kidney injury (AKI) on day 3 of PICU stay. A measured or height-imputed baseline serum creatinine (SCr) is required for AKI diagnosis and RAI calculation, yet these are often lacking. We assessed an age-based, height-independent baseline SCr calculation and compared the RAI values employing this method to their historical counterpart. METHODS: An electronic algorithm was implemented to generate RAI score for patients admitted to our PICU. We reviewed 157 consecutive patient records from May 2017, until we cumulated 100 with a valid RAI calculation. We compared RAI scores using the age-based SCr imputation method of Pottel to the historical RAI. Our primary outcome was a difference in the rate of RAI fulfillment (≥8) reclassification between methods. RESULTS: Of the first 100 patients, 27 had measured baseline SCr and 73 used height imputation. Only two patients had RAI reclassified with the Pottel method (one in each direction). Being small for age or older were associated with ≥25% overestimation of the baseline SCr in 20 patients with the Pottel method compared with height imputation. 15/157 patients had a falsely positive RAI due to lack of measured baseline SCr and height. CONCLUSION: The age-based method to estimate baseline SCr offers a viable height-independent alternative for RAI calculation. While less precise than a height-based approach, this lack of precision rarely leads to reclassification of patient RAI status.

A standardized assessment of response to furosemide is predictive of acute kidney injury progression in adults, but a paucity of data exists in pediatric patients. We evaluate furosemide responsiveness in a multicenter cohort of pediatric patients after cardiac surgery.Children who underwent cardiac surgery with a Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery score of 3 or greater were retrospectively identified. The first dose of furosemide after surgery was recorded, and hourly urine output for 6 hours was recorded after the index dose. Urine flow rate calculated as urine output per hour was used to predict development of acute kidney injury.A total of 166 patients from 4 institutions (median age, 6.3 months; interquartile range, 0.4-27.7) were included. Acute kidney injury occurred in 54 patients (33%). Compared with those without acute kidney injury, the 2- and 6-hour urine flow rates were significantly lower in patients in whom acute kidney injury developed: 2.9 (0.9-6.5) versus 5.0 (2.5-9.0) mL/kg/h for 2-hour urine flow rate, P = .004, and 2.4 (1.2-4.0) versus 4.0 (2.3-5.9) mL/kg/h for 6-hour flow rate, P = .001. In multivariable regression analysis, 2-hour (odds ratio, 1.2, P = .002) and 6-hour (odds ratio, 1.40, P .001) urine flow rates were independently associated with acute kidney injury development. Lower urine flow rate at both 2 and 6 hours was also independently associated with longer hospital length of stay.Lower urine flow rate after furosemide administration, when evaluated in a heterogeneous cohort of children from multiple institutions after pediatric cardiac surgery, was independently associated with subsequent acute kidney injury and longer length of stay. Future prospective studies are needed to validate furosemide responsiveness as a predictor of acute kidney injury.

Consensus definitions for acute kidney injury are based on changes in serum creatinine and urine output. Although the creatinine criteria have been widely applied, the contribution of the urine output criteria remains poorly understood. We evaluated these criteria individually and collectively to determine their impact on the diagnosis and outcome of severe acute kidney injury.Post hoc analysis of Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology study-a prospective international observational multicenter study.Critically ill children enrolled in Assessment of Worldwide Acute Kidney Injury, Renal Angina and, Epidemiology database.To assess the differential impact of creatinine and urine output criteria on severe acute kidney injury (Kidney Disease: Improving Global Outcomes stage ≥ 2). Patients were divided into four cohorts: no-severe acute kidney injury, severe acute kidney injury by creatinine criteria only, severe acute kidney injury by urine output criteria only, and severe acute kidney injury by both creatinine and urine output criteria.Severe acute kidney injury occurred in 496 of 3,318 children (14.9%); 343 (69.2%) were creatinine criteria only, 90 (18.1%) were urine output criteria only, and 63 (12.7%) were both creatinine and urine output criteria. Twenty-eight-day mortality for creatinine criteria only and urine output criteria only patients was similar (6.7% vs 7.8%) and higher than those without severe acute kidney injury (2.9%; p0.01). Both creatinine and urine output criteria patients had higher mortality than creatinine criteria only and urine output criteria only patients (38.1%; p0.001). Compared with patients without severe acute kidney injury, the relative risk of receiving dialysis increased from 9.1 (95% CI, 3.9-21.2) in creatinine criteria only, to 28.2 (95% CI, 11.8-67.7) in urine output criteria only, to 165.7 (95% CI, 86.3-318.2) in both creatinine and urine output criteria (p0.01).Nearly one in five critically ill children with acute kidney injury do not experience increase in serum creatinine. These acute kidney injury events, which are only identified by urine output criteria, are associated with comparably poor outcomes as those diagnosed by changes in creatinine. Children meeting both criteria had worse outcomes than those meeting only one. We suggest oliguria represents a risk factor for poorer outcomes among children who develop acute kidney injury. Application of both the creatinine and urine output criteria leads to a more comprehensive epidemiologic assessment of acute kidney injury and identifies a subset of children with acute kidney injury who are at higher risk for morbidity and mortality.