Epidemiology of acute kidney injury in children: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

The nephrology and critical care communities have seen an increase in studies exploring acute kidney injury (AKI) epidemiology in children. As a result, we now know that AKI is highly prevalent in critically ill neonates, children, and young adults. Furthermore, children who develop AKI experience greater morbidity and higher mortality. Yet knowledge gaps still exist that suggest a more comprehensive understanding of AKI will form the foundation for future efforts designed to improve outcomes. In particular, the areas of community acquired AKI, AKI in non-critically ill children, and cohorts from low-middle income countries have not been well studied. Longer-term functional outcomes and patient-centric metrics including social determinants of health, quality of life, and healthcare utilization should be the foci of the next phase of scholarship. Current definitions identify AKI-based upon evidence of dysfunction which serves as a proxy for injury; biomarkers capable of identifying injury as it occurs are likely to more accurately define populations with AKI. Despite the strength of the association, the causal and mechanistic relationships between AKI and poorer outcomes remain inadequately examined. A more robust understanding of the relationship represents a potential to identify therapeutic targets. Once established, a more comprehensive understanding of AKI epidemiology in children will allow investigation of preventive, therapeutic, and quality improvement interventions more effectively.

Pediatric AKI in the real world: changing outcomes through education and advocacy-a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

BACKGROUND: Acute kidney injury (AKI) is independently associated with increased morbidity and mortality across the life course, yet care for AKI remains mostly supportive. Raising awareness of this life-threatening clinical syndrome through education and advocacy efforts is the key to improving patient outcomes. Here, we describe the unique roles education and advocacy play in the care of children with AKI, discuss the importance of customizing educational outreach efforts to individual groups and contexts, and highlight the opportunities created through innovations and partnerships to optimize lifelong health outcomes. METHODS: During the 26th Acute Disease Quality Initiative (ADQI) consensus conference, a multidisciplinary group of experts discussed the evidence and used a modified Delphi process to achieve consensus on recommendations on AKI research, education, practice, and advocacy in children. RESULTS: The consensus statements developed in response to three critical questions about the role of education and advocacy in pediatric AKI care are presented here along with a summary of available evidence and recommendations for both clinical care and research. CONCLUSIONS: These consensus statements emphasize that high-quality care for patients with AKI begins in the community with education and awareness campaigns to identify those at risk for AKI. Education is the key across all healthcare and non-healthcare settings to enhance early diagnosis and develop mitigation strategies, thereby improving outcomes for children with AKI. Strong advocacy efforts are essential for implementing these programs and building critical collaborations across all stakeholders and settings.

Impact of the Magnitude and Timing of Fluid Overload on Outcomes in Critically Ill Children: A Report From the Multicenter International Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology (AWARE) Study.

OBJECTIVES: With the recognition that fluid overload (FO) has a detrimental impact on critically ill children, the critical care nephrology community has focused on identifying clinically meaningful targets for intervention. The current study aims to evaluate the epidemiology and outcomes associated with FO in an international multicenter cohort of critically ill children. The current study also aims to evaluate the association of FO at predetermined clinically relevant thresholds and time points (FO ≥ 5% and FO ≥ 10% at the end of ICU days 1 and 2) with outcomes. DESIGN: Prospective cohort study. SETTING: Multicenter, international collaborative of 32 pediatric ICUs. PATIENTS: A total of 5,079 children and young adults admitted consecutively to pediatric ICUs as part of the Assessment of the Worldwide Acute Kidney Injury, Renal Angina and Epidemiology Study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The FO thresholds at the time points of interest occurred commonly in the cohort (FO ≥ 5%Day1 in 38.1% [ n = 1753], FO ≥ 10%Day1 in 11.7% [ n = 537], FO ≥ 5%Day2 in 53.3% [ n = 1,539], FO ≥ 10%Day2 in 25.1% [ n = 724]). On Day1, multivariable modeling demonstrated that FO ≥ 5% was associated with fewer ICU-free days, and FO ≥ 10% was associated with higher mortality and fewer ICU and ventilator-free days. On multivariable modeling, FO-peak, Day2 FO ≥ 5%, and Day2 FO ≥ 10% were associated with higher mortality and fewer ICU and ventilator-free days. CONCLUSIONS: This study found that mild-to-moderate FO as early as at the end of ICU Day1 is associated with adverse outcomes. The current study fills an important void in the literature by identifying critical combinations of FO timing and quantity associated with adverse outcomes (FO ≥ 5%Day1, FO ≥10%Day1, FO ≥ 5%Day2, and FO ≥ 10%Day2). Those novel findings will help guide the development of interventional strategies and trials targeting the treatment and prevention of clinically relevant FO.

Prevalence and Characteristics of Diagnostic Error in Pediatric Critical Care: A Multicenter Study.

OBJECTIVES: Effective interventions to prevent diagnostic error among critically ill children should be informed by diagnostic error prevalence and etiologies. We aimed to determine the prevalence and characteristics of diagnostic errors and identify factors associated with error in patients admitted to the PICU. DESIGN: Multicenter retrospective cohort study using structured medical record review by trained clinicians using the Revised Safer Dx instrument to identify diagnostic error (defined as missed opportunities in diagnosis). Cases with potential errors were further reviewed by four pediatric intensivists who made final consensus determinations of diagnostic error occurrence. Demographic, clinical, clinician, and encounter data were also collected. SETTING: Four academic tertiary-referral PICUs. PATIENTS: Eight hundred eighty-two randomly selected patients 0-18 years old who were nonelectively admitted to participating PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 882 patient admissions, 13 (1.5%) had a diagnostic error up to 7 days after PICU admission. Infections (46%) and respiratory conditions (23%) were the most common missed diagnoses. One diagnostic error caused harm with a prolonged hospital stay. Common missed diagnostic opportunities included failure to consider the diagnosis despite a suggestive history (69%) and failure to broaden diagnostic testing (69%). Unadjusted analysis identified more diagnostic errors in patients with atypical presentations (23.1% vs 3.6%, p = 0.011), neurologic chief complaints (46.2% vs 18.8%, p = 0.024), admitting intensivists greater than or equal to 45 years old (92.3% vs 65.1%, p = 0.042), admitting intensivists with more service weeks/year (mean 12.8 vs 10.9 wk, p = 0.031), and diagnostic uncertainty on admission (77% vs 25.1%, p < 0.001). Generalized linear mixed models determined that atypical presentation (odds ratio [OR] 4.58; 95% CI, 0.94-17.1) and diagnostic uncertainty on admission (OR 9.67; 95% CI, 2.86-44.0) were significantly associated with diagnostic error. CONCLUSIONS: Among critically ill children, 1.5% had a diagnostic error up to 7 days after PICU admission. Diagnostic errors were associated with atypical presentations and diagnostic uncertainty on admission, suggesting possible targets for intervention.

An update on the role of fluid overload in the prediction of outcome in acute kidney injury.

Over the past two decades, our understanding of the impact of acute kidney injury, disorders of fluid balance, and their interplay have increased significantly. In recent years, the epidemiology and impact of fluid balance, including the pathologic state of fluid overload on outcomes has been studied extensively across multiple pediatric and neonatal populations. A detailed understating of fluid balance has become increasingly important as it is recognized as a target for intervention to continue to work to improve outcomes in these populations. In this review, we provide an update on the epidemiology and outcomes associated with fluid balance disorders and the development of fluid overload in children with acute kidney injury (AKI). This will include a detailed review of consensus definitions of fluid balance, fluid overload, and the methodologies to define them, impact of fluid balance on the diagnosis of AKI and the concept of fluid corrected serum creatinine. This review will also provide detailed descriptions of future directions and the changing paradigms around fluid balance and AKI in critical care nephrology, including the incorporation of the sequential utilization of risk stratification, novel biomarkers, and functional kidney tests (furosemide stress test) into research and ultimately clinical care. Finally, the review will conclude with novel methods currently under study to assess fluid balance and distribution (point of care ultrasound and bioimpedance).

Synergistic association of fluid overload and acute kidney injury on outcomes in pediatric cardiac ECMO: a retrospective analysis of the KIDMO database.

BACKGROUND: Acute kidney injury (AKI) and fluid overload (FO) are associated with poor outcomes in children receiving extracorporeal membrane oxygenation (ECMO). Our objective is to evaluate the impact of AKI and FO on pediatric patients receiving ECMO for cardiac pathology. METHODS: We performed a secondary analysis of the six-center Kidney Interventions During Extracorporeal Membrane Oxygenation (KIDMO) database, including only children who underwent ECMO for cardiac pathology. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria. FO was defined as < 10% (FO-) vs. ≥ 10% (FO +) and was evaluated at ECMO initiation, peak during ECMO, and ECMO discontinuation. Primary outcomes were mortality and length of stay (LOS). RESULTS: Data from 191 patients were included. Non-survivors (56%) were more likely to be FO + than survivors at peak ECMO fluid status and ECMO discontinuation. There was a significant interaction between AKI and FO. In the presence of AKI, the adjusted odds of mortality for FO + was 4.79 times greater than FO- (95% CI: 1.52-15.12, p = 0.01). In the presence of FO + , the adjusted odds of mortality for AKI + was 2.7 times higher than AKI- [95%CI: 1.10-6.60; p = 0.03]. Peak FO + was associated with a 55% adjusted relative increase in LOS [95%CI: 1.07-2.26, p = 0.02]. CONCLUSIONS: The association of peak FO + with mortality is present only in the presence of AKI + . Similarly, AKI + is associated with mortality only in the presence of peak FO + . FO + was associated with LOS. Studies targeting fluid management have the potential to improve LOS and mortality outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Consensus acute kidney injury criteria integration identifies children at risk for long-term kidney dysfunction after multiple organ dysfunction syndrome.

BACKGROUND: The consensus definition of acute kidney injury (AKI) has evolved since developing the original multiple organ dysfunction syndrome (MODS) definitions. Whether or not risk for adverse short- and long-term outcomes can be identified using the refined AKI criteria in the setting of MODS has not been studied. We hypothesize that incorporation of Kidney Disease: Improving Global Outcome (KDIGO) AKI criteria into existing MODS definitions will have a higher association with major adverse kidney events at 30 days (MAKE30) and will increase the number of patients with MODS. METHODS: Post hoc analysis of 410 children admitted to a tertiary care pediatric intensive care unit (PICU) was conducted. MODS was defined using two existing criteria (Goldstein and Proulx) during the first 7 days following ICU admission and then modified by replacement of the kidney injury criteria using the KDIGO AKI definitions (G' and P'). RESULTS: MAKE30 occurred in 65 of 410 (16%) children. After substituting KDIGO kidney injury criteria, identification of MAKE30 increased from 46 children (71%) to 53 (82%) and 29 children (45%) to 43 (66%) for the Goldstein and Proulx criteria, respectively. Additionally, identification of MODS increased from 194 (47%) by Goldstein to 224 (55%) by G' and 95 children (23%) by Proulx to 132 (32%) by P'. CONCLUSIONS: Substituting KDIGO AKI criteria into existing MODS criteria increases the sensitivity for major adverse kidney events as well as the identification of MODS, improving the detection of children at risk for long-term adverse renal outcomes.

Renal angina index predicts fluid overload in critically ill children: an observational cohort study.

BACKGROUND: Fluid overload and acute kidney injury are common and associated with poor outcomes among critically ill children. The prodrome of renal angina stratifies patients by risk for severe acute kidney injury, but the predictive discrimination for fluid overload is unknown. METHODS: Post-hoc analysis of patients admitted to a tertiary care pediatric intensive care unit (PICU). The primary outcome was the performance of renal angina fulfillment on day of ICU admission to predict fluid overload ≥15% on Day 3. RESULTS: 77/139 children (55%) fulfilled renal angina (RA+). After adjusting for covariates, RA+ was associated with increased odds of fluid overload on Day 3 (adjusted odds ratio (aOR) 5.1, 95% CI 1.23-21.2, p = 0.025, versus RA-). RA- resulted in a 90% negative predictive value for fluid overload on Day 3. Median fluid overload was significantly higher in RA+ patients with severe acute kidney injury compared to RA+ patients without severe acute kidney injury (% fluid overload on Day 3: 8.8% vs. 0.73%, p = 0.002). CONCLUSION: Among critically ill children, fulfillment of renal angina was associated with increased odds of fluid overload versus the absence of renal angina and a higher fluid overload among patients who developed acute kidney injury. Renal angina directed risk classification may identify patients at highest risk for fluid accumulation. Expanded study in larger populations is warranted.

Clinician Accuracy in Identifying and Predicting Organ Dysfunction in Critically Ill Children.

OBJECTIVES: To determine clinician accuracy in the identification and prediction of multiple organ dysfunction syndrome. DESIGN: Prospective cohort study. SETTING: University of Michigan's C.S. Mott Children's Hospital PICU. PATIENTS: Patients admitted to the PICU with an anticipated PICU length of stay greater than 48 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For each patient, the clinical team (attending, fellow, resident/nurse practitioner) was surveyed regarding existing and anticipated organ dysfunction. The primary outcomes were clinicians' accuracy at identifying multiple organ dysfunction syndrome and predicting new or progressive multiple organ dysfunction syndrome, compared to the objective assessment of multiple organ dysfunction syndrome using Proulx criteria. We also measured sensitivity, specificity, negative and positive predictive values, and negative and positive likelihood ratios of clinician assessments. We tested for differences in accuracy by clinician type using chi-square tests. Clinicians rated their confidence in prediction on a 5-point Likert scale. There were 476 eligible PICU admissions, for whom 1,218 surveys were completed. Multiple organ dysfunction syndrome was present in 89 patients (18.7%) at enrollment, and new or progressive multiple organ dysfunction syndrome occurred in 39 (8.2%). Clinicians correctly identified multiple organ dysfunction syndrome with 79.9% accuracy and predicted additional organ dysfunction with 82.6% accuracy. However, the positive and negative likelihood ratios for new or progressive multiple organ dysfunction syndrome prediction were 3.0 and 0.7, respectively, indicating a weak relationship between the clinician prediction and development of new or progressive multiple organ dysfunction syndrome. The positive predictive value of new or progressive multiple organ dysfunction syndrome prediction was just 22.1%. We found no differences in accuracy by clinician type for either identification of multiple organ dysfunction syndrome (80.2% vs 78.2% vs 81.0%; p = 0.57) or prediction of new or progressive multiple organ dysfunction syndrome (84.8% vs 82.8% vs 80.3%; p = 0.26) for attendings, fellows, and residents/nurse practitioners, respectively. There was a weak correlation between the confidence and accuracy of prediction (pairwise correlation coefficient, 0.26; p < 0.001). CONCLUSIONS: PICU clinicians correctly identified multiple organ dysfunction syndrome and predicted new or progressive multiple organ dysfunction syndrome with 80% accuracy. However, only 8% of patients developed new or progressive multiple organ dysfunction syndrome, so accuracy was largely due to true negative predictions. The positive predictive value for new or progressive multiple organ dysfunction syndrome prediction was just 22%. Accuracy did not differ by clinician type, but was correlated with self-rated confidence and was higher for negative predictions.

Fluid overload and fluid removal in pediatric patients on extracorporeal membrane oxygenation requiring continuous renal replacement therapy: a multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to characterize continuous renal replacement therapy (CRRT) utilization on extracorporeal membrane oxygenation (ECMO) and to determine the association of both fluid overload (FO) at CRRT initiation and fluid removal during CRRT with mortality in a large multicenter cohort. METHODS: Retrospective chart review of all children < 18 years of age concurrently treated with ECMO and CRRT from January 1, 2007, to December 31, 2011, at six tertiary care children's hospital. Children treated with hemodialysis or peritoneal dialysis were excluded from the FO analysis. MEASUREMENTS AND MAIN RESULTS: A total of 756 of the 1009 children supported with ECMO during the study period had complete FO data. Of these, 357 (47.2%) received either CRRT or were treated with an in-line filter and thus entered into the final analysis. Survival to ECMO decannulation was 66.4% and survival to hospital discharge was 44.3%. CRRT initiation occurred at median of 1 day (IQR 0, 2) after ECMO initiation. Median FO at CRRT initiation was 20.1% (IQR 5, 40) and was significantly lower in ECMO survivors vs. non-survivors (15.3% vs. 30.5% p = 0.005) and in hospital survivors vs. non-survivors (13.5% vs. 25.9%, p = 0.004). Median FO at CRRT discontinuation was significantly lower in ECMO survivors (23% vs. 37.6% p = 0.002) and hospital survivors vs. non-survivors (22.6% vs. 36.1%, p = 0.002). In ECMO survivors, after adjusting for pH at CRRT initiation, non-renal complications, ECMO mode, support type, center, patient age and AKI, FO at CRRT initiation (p = 0.01), and FO at CRRT discontinuation (p = 0.0002) were independently associated with duration of ECMO. In a similar multivariable analysis, FO at CRRT initiation (adjusted adds ratio [aOR] 1.09, 95% CI 1.00-1.18, p = 0.045) and at CRRT discontinuation (aOR 1.11, 95% CI 1.03-1.19, p = 0.01) were independently associated with hospital mortality. CONCLUSIONS: In a multicenter pediatric ECMO cohort, this study demonstrates that severe FO was very common at CRRT initiation. We found an independent association between the degree of FO at CRRT initiation with adverse outcomes including mortality and increased duration of ECMO support. The results suggest that intervening prior to the development of significant FO may be a clinical therapeutic target and warrants further evaluation.

Corrigendum to "Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK)" [Kidney International Reports Volume 8, Issue 8, August 2023, Pages 1542-1552].

[This corrects the article DOI: 10.1016/j.ekir.2023.05.026.].

Definitions of adverse events associated with extracorporeal membrane oxygenation in children: results of an international Delphi process from the ECMO-CENTRAL ARC.

Extracorporeal membrane oxygenation (ECMO) is a high-risk and low-volume life support with increasing clinical study. However, heterogenous outcome definitions impede data assimilation into evidence to guide practice. The Academic Research Consortium (ARC), an international collaborative forum committed to facilitating the creation of stakeholder-driven consensus nomenclature and outcomes for clinical trials of medical devices, supported the ECMO Core Elements Needed for Trials Regulation And quality of Life (ECMO-CENTRAL) ARC. The ECMO-CENTRAL ARC was assembled to develop definitions of paediatric ECMO adverse events for use in clinical trials and regulatory device evaluation. An initial candidate list of ECMO adverse events derived from the mechanical circulatory support ARC was supplemented with a review of ECMO-relevant adverse event definitions collated from literature published between Jan 1, 1988, and Feb 20, 2023. Distinct teams of international topic experts drafted separate adverse event definitions that were harmonised to existing literature when appropriate. Draft definitions were revised for paediatric ECMO relevance with input from patients, families, and an international expert panel of trialists, clinicians, statisticians, biomedical engineers, device developers, and regulatory agencies. ECMO-CENTRAL ARC was revised and disseminated across research societies and professional organisations. Up to three rounds of internet-based anonymous surveys were planned as a modified Delphi process. The expert panel defined 13 adverse event definitions: neurological, bleeding, device malfunction, acute kidney injury, haemolysis, infection, vascular access-associated injury, non-CNS thrombosis, hepatic dysfunction, right heart failure, left ventricular overload, lactic acidaemia, and hypoxaemia. Definitional structure varied. Among 165 expert panel members, 114 were eligible to vote and 111 voted. Consensus was achieved for all proposed definitions. Agreement ranged from 82% to 95%. ECMO-CENTRAL ARC paired rigorous development with methodical stakeholder involvement and dissemination to define paediatric ECMO adverse events. These definitions will facilitate new research and the assimilation of data across clinical trials and ECMO device evaluation in children.

Hospital ECMO capability is associated with survival in pediatric cardiac arrest.

AIM: Extracorporeal membrane oxygenation (ECMO) provides temporary support in severe cardiac or respiratory failure and can be deployed in children who suffer cardiac arrest. However, it is unknown if a hospital's ECMO capability is associated with better outcomes in cardiac arrest. We evaluated the association between pediatric cardiac arrest survival and the availability of pediatric extracorporeal membrane oxygenation (ECMO) at the treating hospital. METHODS: We identified cardiac arrest hospitalizations, including in- and out-of-hospital, in children (0-18 years old) using data from the Health Care Utilization Project (HCUP) National Inpatient Sample (NIS) between 2016 and 2018. The primary outcome was in-hospital survival. Hierarchical logistic regression models were built to test the association between hospital ECMO capability and in-hospital survival. RESULTS: We identified 1276 cardiac arrest hospitalizations. Survival of the cohort was 44%; 50% at ECMO-capable hospitals and 32% at non-ECMO hospitals. After adjusting for patient-level factors and hospital factors, receipt of care at an ECMO- capable hospital was associated with higher in-hospital survival, with an odds ratio of 1.49 [95% CI 1.09, 2.02]. Patients who received treatment at ECMO-capable hospitals were younger (median 3 years vs 11 years, p < 0.001) and more likely to have a complex chronic condition, specifically congenital heart disease. A total of 10.9% (88/811) of patients at ECMO-capable hospitals received ECMO support. CONCLUSION: A hospital's ECMO capability was associated with higher in-hospital survival among children suffering cardiac arrest in this analysis of a large United States administrative dataset. Future work to understand care delivery differences and other organizational factors in pediatric cardiac arrest is necessary to improve outcomes.

Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK).

Introduction: Continuous renal replacement therapy (CRRT) is used for the symptomatic management of acute kidney injury (AKI) and fluid overload (FO). Contemporary reports on pediatric CRRT are small and single center in design. Large international studies evaluating CRRT practice and outcomes are lacking. Herein, we describe the design of a multinational collaborative. Methods: The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) is an international collaborative of pediatric specialists whose mission is to improve short- and long-term outcomes of children treated with CRRT. The aims of this multicenter retrospective study are to describe the epidemiology, liberation patterns, association of fluid balance and timing of CRRT initiation, and CRRT prescription with outcomes. Results: We included children (n = 996, 0-25 years) admitted to an intensive care unit (ICU) and treated with CRRT for AKI or FO at 32 centers (in 7 countries) from 2018 to 2021. Demographics and clinical characteristics before CRRT initiation, during the first 7 days of both CRRT, and liberation were collected. Outcomes include the following: (i) major adverse kidney events at 90 days (mortality, dialysis dependence, and persistent kidney dysfunction), and (ii) functional outcomes (functional stats scale). Conclusion: The retrospective WE-ROCK study represents the largest international registry of children receiving CRRT for AKI or FO. It will serve as a broad and invaluable resource for the field of pediatric critical care nephrology that will improve our understanding of practice heterogeneity and the association of CRRT with clinical and patient-centered outcomes. This will generate preliminary data for future interventional trials in this area.

Renal Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

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 <0.5 mL/kg per hour for ≥6 hours and serum creatinine increase of 1.5 to 1.9 times baseline or ≥0.3 mg/dL, or (2) urine output <0.5 mL/kg per hour for ≥12 hours, or (3) serum creatinine increase ≥2 times baseline, or (4) estimated glomerular filtration rate <35 mL/minute/1.73 m2, or (5) initiation of renal replacement therapy, or (6) fluid overload ≥20%. Data also support criteria for persistent renal dysfunction and for high risk of renal dysfunction. LIMITATIONS: All included studies were observational and many were retrospective. CONCLUSIONS: We present consensus criteria for renal dysfunction in critically ill children.

Fluid Balance Management Informs Renal Replacement Therapy Use During Pediatric Extracorporeal Membrane Oxygenation: A Survey Report From the Kidney Intervention During Extracorporeal Membrane Oxygenation Group.

Fluid overload (FO) and acute kidney injury (AKI) occur commonly in children supported with extracorporeal membrane oxygenation (ECMO). Continuous renal replacement therapy (CRRT) may be used to manage AKI and FO in children on ECMO. In 2012, our group surveyed ECMO centers to begin to understand the practice patterns around CRRT and ECMO. Since then, more centers are initiating ECMO for increasingly diverse indications and an increased volume of research quantifies the detrimental impacts of AKI and FO. We, therefore, investigated practice patterns of CRRT utilization during ECMO in children. A multi-point survey instrument was distributed to 116 international neonatal and pediatric ECMO centers. Sixty of 116 (51.7%) international neonatal and pediatric ECMO centers responded. All reports using CRRT on ECMO, compared with 75% from the 2012 survey. Eighty-five percent use CRRT to treat or prevent FO, an increased from 59%. The modality of CRRT therapy differed between in-line (slow continuous ultrafiltration, 84.4%) and machine-based (continuous venovenous hemodiafiltration, 87.3%) methods. Most (65%) do not have protocols for fluid management, AKI, or CRRT on ECMO. Trialing off CRRT is dictated by physician preference in 90% (54/60), with varying definitions of success. In this survey study, we found that CRRT use during pediatric ECMO has increased since 2012 with fluid management representing the predominant indication for initiation. Despite the expanded utilization of CRRT with ECMO, there remains significant practice variation in terms of method, modality, indication, the timing of initiation, fluid management, and discontinuation.

Acute Kidney Injury and Fluid Overload in Pediatric Extracorporeal Cardio-Pulmonary Resuscitation: A Multicenter Retrospective Cohort Study.

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 <10% [FO-] vs. ≥10% [FO+] evaluated at ECMO initiation and discontinuation. A composite exposure, defined by a four-group discrete phenotypic classification [FO-/AKI-, FO-/AKI+, FO+/AKI-, FO+/AKI+] was also evaluated. Primary outcome was mortality and hospital length of stay (LOS) among survivors. 131 patients (median age 29 days (IQR:9, 242 days); 51% men and 82% with underlying cardiac disease) were included. 45.8% survived hospital discharge. FO+ at ECMO discontinuation, but not AKI was associated with mortality [aOR=2.3; 95% CI: 1.07-4.91]. LOS for FO+ patients was twice as long as FO- patients, irrespective of AKI status [(FO+/AKI+ (60 days; IQR: 49-83) vs. FO-/AKI+ (30 days, IQR: 19-48 days); P = 0.01]. FO+ at ECMO initiation and discontinuation was associated with an adjusted 66% and 50% longer length of stay respectively. Prospective studies that target timing and strategy of fluid management, including its removal in children receiving ECPR are greatly needed.

Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children: A Modified Delphi Consensus Statement.

Importance: Increasing 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. Objective: To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy. Evidence Review: At 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. Findings: The 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 Relevance: Existing 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.

Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary.

Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.