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Introduction: Critically ill admitted patients are at high risk of acute kidney injury (AKI). The renal angina index (RAI) and urinary biomarker neutrophil gelatinase-associated lipocalin (uNGAL) can aid in AKI risk assessment. We implemented the Trial in AKI using NGAL and Fluid Overload to optimize CRRT Use (TAKING FOCUS 2; TF2) to personalize fluid management and continuous renal replacement therapy (CRRT) initiation based on AKI risk and patient fluid accumulation. We compared outcomes pre-TF2 and post-TF2 initiation. Methods: Patients admitted from July 2017 were followed-up prospectively with the following: (i) an automated RAI result at 12 hours of admission, (ii) a conditional uNGAL order for RAI ≥8, and (iii) a CRRT initiation goal at 10% to 15% weight-based fluid accumulation. Results: A total of 286 patients comprised 304 intensive care unit (ICU) RAI+ admissions; 178 patients received CRRT over the observation period (2014–2021). Median time from ICU admission to CRRT initiation was 2 days shorter (P < 0.002), and ≥15% pre-CRRT fluid accumulation rate was lower in the TF2 era (P < 0.02). TF2 ICU length of stay (LOS) after CRRT discontinuation and total ICU LOS were 6 and 11 days shorter for CRRT survivors (both P < 0.02). Survival rates to ICU discharge after CRRT discontinuation were higher in the TF2 era (P = 0.001). These associations persisted in each TF2 year; we estimate a conservative $12,500 health care cost savings per CRRT patient treated after TF2 implementation. Conclusion: We suggest that automated clinical decision support (CDS) combining risk stratification and AKI biomarker assessment can produce durable reductions in pediatric CRRT patient morbidity.

Rationale and Objective: Critically ill children with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) are at increased risk of death. The selective cytopheretic device (SCD) promotes an immunomodulatory effect at circuit-ionized calcium of

Abstract 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.

We propose a novel metric evaluating the impact an exposure to a large positive fluid balance over time has on clinical outcomes in children with respiratory failure, termed “fluid overload mechanically ventilated” (FOMV) days. We performed a retrospective cohort study of mechanically ventilated children. Using multivariable regression analyses, each FOMV day was associated with a 5% decreased likelihood of having a ventilator-free day (adjusted incidence rate ratio [aIRR], 0.95; 95% CI, 0.95–0.96), a 5% increased likelihood of having an additional day of stay (aIRR, 1.05; 95% CI 1.05–1.06), and a 6% increased relative risk of death (aRR, 1.06; 95% CI, 1.01–1.11). FOMV is a novel exposure measure in children with acute respiratory failure associated with poor outcomes paralleling published data demonstrating dose-dependent exposure to a positive fluid balance is associated with worse outcomes. FOMV is a targetable exposure metric for future use in quality improvement initiatives and research studies that may help to determine the efficacy of interventions.

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.

Abstract Background The prevalence of continuous renal replacement therapy (CRRT) utilization in critically ill patients with acute kidney is increasing. In comparison to published and on-going trials attempting to answer questions surrounding the optimal timing of CRRT initiation, anticoagulation, and modality, a paucity of literature describes the quality of the therapy delivered. Methods We conducted a single-center process improvement project to determine if a methodology to assess the quality of CRRT delivery could lead to improvement in CRRT delivery outcomes. We developed three broad categories of objective CRRT metrics to assess longitudinally, enabling creation of a CRRT Dashboard. Following the objective categories of “filter”, “prescription”, and “fluid balance” over time allowed us to perform quarterly analyses, target provider based CRRT education, and address variation from our standard of care. From 2012 to 2017, 184 critically ill patients received CRRT. Results We report a mean filter life of 56 + 28.4 h, a 60-h filter life of 62%, and unplanned filter changes of 15%. Compared to a minimum target prescription of 2000 ml/1.73 m2/hour, we report the mean prescribed dose (2300 ml/1.73 m2/hour) and the rate of patients receiving at least the minimum prescription (98%). Finally, using a 10% deviation in the acceptable range of desired daily patient fluid balance, we report 83% CRRT patient days achieving an acceptable stipulated fluid goal. Conclusion We report the implementation of a quality dashboard and adopting quality improvement strategies provided a platform for measuring adherence to our institutional standards and the delivery of CRRT, specifically on the process of the care.

Acute kidney injury (AKI) affects one in four neonates, children, and adults admitted to the intensive care unit (ICU). AKI-associated outcomes, including mortality, are significantly worsened. Several decades of research demonstrate evidence for a need to rethink the pathophysiology and drivers of injury as well as to reconsider the existing diagnostic framework. Novel urinary and serum biomarkers of injury have, however, not been readily integrated into practice—partially because of the limited scope to current testing. The predominant focus to date has been the adjudication of a single biomarker measured at a single point of time for the prediction of either AKI progression or disease-related mortality. This approach is pragmatically problematic. The imprecise, umbrella classification of AKI diagnosis coupled with the absence of a consistently effective set of therapies creates a difficult rubric for biomarkers to demonstrate value in the scope of practice. AKI is, however, not a binary process but more an ICU syndrome—with complex biology underpinning injury, interacting and disrupting other organ function, multidimensional in manifestation, and varying in severity over time. As such, a more appropriate diagnostic paradigm is needed. In this minireview, the status quo for AKI diagnosis and associated limitations will be discussed, and a novel, dynamic, and multidimensional paradigm will be presented. Appreciation of AKI as an ICU syndrome and creation of an appropriately matching and sophisticated diagnostic platform of injury assessment are possible and represent the next step in AKI management.

Background: Fluid therapy is a mainstay during the resuscitation of critically ill children. After initial stabilization, excessive fluid accumulation may lead to complications of fluid overload, which has been independently associated with increased risk for mortality and major morbidity in critically ill children. Objectives: Perform an evidence synthesis to describe the methods used to measure fluid balance, define fluid overload, and evaluate the association between fluid balance and outcomes in critically ill children. Design: Systematic review and meta-analysis. Measurements: Fluid balance, fluid accumulation, and fluid overload as defined by authors. Methods: We will search Ovid MEDLINE, Ovid EMBASE, Cochrane Library, and ProQuest, Dissertations and Theses. In addition, we will search www.clinicaltrials.gov , World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and the proceedings of selected key conferences for ongoing and completed studies. Search strategy will be done in consultation with a research librarian. Clinical trials and observational studies (from database inception to present) in patients (

Purpose of review: The purpose of this review is to report how administrative data have been used to study AKI, identify current limitations, and suggest how these data sources might be enhanced to address knowledge gaps in the field. Objectives: 1) To review the existing evidence-base on how AKI is coded across administrative datasets, 2) To identify limitations, gaps in knowledge, and major barriers to scientific progress in AKI related to coding in administrative data, 3) To discuss how administrative data for AKI might be enhanced to enable “communication” and “translation” within and across administrative jurisdictions, and 4) To suggest how administrative databases might be configured to inform ‘registry-based’ pragmatic studies. Source of information: Literature review of English language articles through PubMed search for relevant AKI literature focusing on the validation of AKI in administrative data or used administrative data to describe the epidemiology of AKI. Setting: Acute Dialysis Quality Initiative (ADQI) Consensus Conference September 6-7 th , 2015, Banff, Canada Patients: Hospitalized patients with AKI Key messages: The coding structure for AKI in many administrative datasets limits understanding of true disease burden (especially less severe AKI) its temporal trends and clinical phenotyping. Important opportunities exist to improve the quality and coding of AKI data to better address critical knowledge gaps in AKI and improve care. Methods: A modified Delphi consensus building process consisting of review of the literature and summary statements were developed through a series of alternating breakout and plenary sessions. Results: Administrative codes for AKI are limited by poor sensitivity, lack of standardization to classify severity, and poor contextual phenotyping. These limitations are further hampered by reduced awareness of AKI among providers and the subjective nature of reporting. While an idealized definition of AKI may be difficult to implement, improving standardization of reporting by using laboratory-based definitions and providing complementary information on the context in which AKI occurs are possible. Administrative databases may also help enhance the conduct of and inform clinical or registry-based pragmatic studies. Limitations: Data sources largely restricted to North American and Europe Implications: Administrative data are rapidly growing and evolving, and represent an unprecedented opportunity to address knowledge gaps in AKI. Progress will require continued efforts to improve awareness of the impact of AKI on public health, engage key stakeholders, and develop tangible strategies to reconfigure infrastructure to improve the reporting and phenotyping of AKI. Why is this review important?: Rapid growth in the size and availability of administrative data has enhanced the clinical study of acute kidney injury (AKI). However, significant limitations exist in coding that hinder our ability to better understand its epidemiology and address knowledge gaps. The following consensus-based review discusses how administrative data have been used to study AKI, identify current limitations, and suggest how these data sources might be enhanced to improve the future study of this disease. What are the key messages?: The current coding structure of administrative data is hindered by a lack of sensitivity, standardization to properly classify severity, and limited clinical phenotyping. These limitations combined with reduced awareness of AKI and the subjective nature of reporting limit understanding of disease burden across settings and time periods. As administrative data become more sophisticated and complex, important opportunities to employ more objective criteria to diagnose and stage AKI as well as improve contextual phenotyping exist that can help address knowledge gaps and improve care.

Acute kidney injury (AKI) independently increases morbidity and mortality in children admitted to the hospital. Renal replacement therapy (RRT) is an essential therapy in the setting of AKI and fluid overload. The decision to initiate RRT is complex and often complicated by concerns related to patient hemodynamic and thermodynamic instability. The choice of which RRT modality to use depends on numerous criteria that are both patient and treatment center specific. Surprisingly, despite decades of use, no randomized, controlled trial study involving RRT in pediatrics has been performed. Because of these factors, clear-cut consensus is lacking regarding key questions surrounding RRT delivery. In this paper, we will summarize existing data concerning RRT use in children. We discuss the major modalities and the data-driven specifics of each, followed by controversies in RRT. As no standard of care is in widespread use for RRT in AKI or in multiorgan disease, we conclude in this paper that prospective studies of RRT are needed to identify best practice guidelines.

Pulmonary edema worsens the morbidity and increases the mortality of critically ill patients. Mechanistically, edema formation in the lung is a result of net flow across the alveolar capillary membrane, dependent on the relationship of hydrostatic and oncotic pressures. Traditionally, the contribution of acute kidney injury (AKI) to the formation of pulmonary edema has been attributed to bulk fluid accumulation, increasing capillary hydrostatic pressure and the gradient favoring net flow into the alveolar spaces. Recent research has revealed more subtle, and distant, effects of AKI. In this review we discuss the concept of nephrogenic pulmonary edema. Pro-inflammatory gene upregulation, chemokine over-expression, altered biochemical channel function, and apoptotic dysregulation manifest in the lung are now understood as “extra-renal” and pulmonary effects of AKI. AKI should be counted as a disease process that alters the endothelial integrity of the alveolar capillary barrier and has the potential to overpower the ability of the lung to regulate fluid balance. Nephrogenic pulmonary edema, therefore, is the net effect of fluid accumulation in the lung as a result of both the macroscopic and microscopic effects of AKI.