Characteristics and Outcomes of Children and Young Adults With Sepsis Requiring Continuous Renal Replacement Therapy: A Comparative Analysis From the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK).

OBJECTIVES: Pediatric sepsis-associated acute kidney injury (AKI) often requires continuous renal replacement therapy (CRRT), but limited data exist regarding patient characteristics and outcomes. We aimed to describe these features, including the impact of possible dialytrauma (i.e., vasoactive requirement, negative fluid balance) on outcomes, and contrast them to nonseptic patients in an international cohort of children and young adults receiving CRRT. DESIGN: A secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), an international, multicenter, retrospective study. SETTING: Neonatal, cardiac and PICUs at 34 centers in nine countries from January 1, 2015, to December 31, 2021. PATIENTS: Patients 0-25 years old requiring CRRT for AKI and/or fluid overload. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1016 patients, 446 (44%) had sepsis at CRRT initiation and 650 (64%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (defined as a composite of death, renal replacement therapy [RRT] dependence, or > 25% decline in estimated glomerular filtration rate from baseline at 90 d from CRRT initiation). Septic patients were less likely to liberate from CRRT by 28 days (30% vs. 38%; p < 0.001) and had higher rates of MAKE-90 (70% vs. 61%; p = 0.002) and higher mortality (47% vs. 31%; p < 0.001) than nonseptic patients; however, septic survivors were less likely to be RRT dependent at 90 days (10% vs. 18%; p = 0.011). On multivariable regression, pre-CRRT vasoactive requirement, time to negative fluid balance, and median daily fluid balance over the first week of CRRT were not associated with MAKE-90; however, increasing duration of vasoactive requirement was independently associated with increased odds of MAKE-90 (adjusted OR [aOR], 1.16; 95% CI, 1.05-1.28) and mortality (aOR, 1.20; 95% CI, 1.1-1.32) for each additional day of support. CONCLUSIONS: Septic children requiring CRRT have different clinical characteristics and outcomes compared with those without sepsis, including higher rates of mortality and MAKE-90. Increasing duration of vasoactive support during the first week of CRRT, a surrogate of potential dialytrauma, appears to be associated with these outcomes.

Hemoadsorption: Consensus report of the 30th Acute Disease Quality Initiative workgroup.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex-vivo, experimental, and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative (ADQI) consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility, and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials (RCTs). Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

A proposed framework for advancing acute kidney injury risk stratification and diagnosis in children: a report from the 26th Acute Disease Quality Initiative (ADQI) conference.

Acute kidney injury (AKI) in children is associated with increased morbidity, reduced health-related quality of life, greater resource utilization, and higher mortality. Improvements in the timeliness and precision of AKI diagnosis in children are needed. In this report, we highlight existing, novel, and on-the-horizon diagnostic and risk-stratification tools for pediatric AKI, and outline opportunities for integration into clinical practice. We also summarize pediatric-specific high-risk diagnoses and exposures for AKI, as well as the potential role of real-time risk stratification and clinical decision support to improve outcomes. Lastly, the key characteristics of important pediatric AKI phenotypes will be outlined. Throughout, we identify key knowledge gaps, which represent prioritized areas of focus for future research that will facilitate a comprehensive, timely and personalized approach to pediatric AKI diagnosis and management.

Concurrent use of continuous kidney replacement therapy during extracorporeal membrane oxygenation: what pediatric nephrologists need to know-PCRRT-ICONIC practice points.

Extracorporeal membrane oxygenation (ECMO) provides temporary cardiorespiratory support for neonatal, pediatric, and adult patients when traditional management has failed. This lifesaving therapy has intrinsic risks, including the development of a robust inflammatory response, acute kidney injury (AKI), fluid overload (FO), and blood loss via consumption and coagulopathy. Continuous kidney replacement therapy (CKRT) has been proposed to reduce these side effects by mitigating the host inflammatory response and controlling FO, improving outcomes in patients requiring ECMO. The Pediatric Continuous Renal Replacement Therapy (PCRRT) Workgroup and the International Collaboration of Nephrologists and Intensivists for Critical Care Children (ICONIC) met to highlight current practice standards for ECMO use within the pediatric population. This review discusses ECMO modalities, the pathophysiology of inflammation during an ECMO run, its adverse effects, various anticoagulation strategies, and the technical aspects and outcomes of implementing CKRT during ECMO in neonatal and pediatric populations. Consensus practice points and guidelines are summarized. ECMO should be utilized in patients with severe acute respiratory failure despite the use of conventional treatment modalities. The Extracorporeal Life Support Organization (ELSO) offers guidelines for ECMO initiation and management while maintaining a clinical registry of over 195,000 patients to assess outcomes and complications. Monitoring and preventing fluid overload during ECMO and CKRT are imperative to reduce mortality risk. Clinical evidence, resources, and experience of the nephrologist and healthcare team should guide the selection of ECMO circuit.

Characteristics and outcomes of children ≤ 10 kg receiving continuous kidney replacement therapy: a WE-ROCK study.

BACKGROUND: Continuous kidney replacement therapy (CKRT) is often used for acute kidney injury (AKI) or fluid overload (FO) in children ≤ 10 kg. Intensive care unit (ICU) mortality in children ≤ 10 kg reported by the prospective pediatric CRRT (ppCRRT, 2001-2003) registry was 57%. We aimed to evaluate characteristics associated with ICU mortality using a contemporary registry. METHODS: The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry is a retrospective, multinational, observational study of children and young adults aged 0-25 years receiving CKRT (2015-2021) for AKI or FO. This analysis included patients ≤ 10 kg at hospital admission. PRIMARY AND SECONDARY OUTCOMES: ICU mortality and major adverse kidney events at 90 days (MAKE-90) defined as death, persistent kidney dysfunction, or dialysis within 90 days, respectively. RESULTS: A total of 210 patients were included (median age 0.53 years (IQR, 0.1, 0.9)). ICU mortality was 46.5%. MAKE-90 occurred in 150/207 (72%). CKRT was initiated at a median 3 days (IQR 1, 9) after ICU admission and lasted a median 6 days (IQR 3, 16). On multivariable analysis, pediatric logistic organ dysfunction score (PELOD-2) at CKRT initiation was associated with increased odds of ICU mortality (aOR 2.64, 95% CI 1.68-4.16), and increased odds of MAKE-90 (aOR 2.2, 95% CI 1.31-3.69). Absence of comorbidity was associated with lower MAKE-90 (aOR 0.29, 95%CI 0.13-0.65). CONCLUSIONS: We report on a contemporary cohort of children ≤ 10 kg treated with CKRT for acute kidney injury and/or fluid overload. ICU mortality is decreased compared to ppCRRT. The extended risk of death and morbidity at 90 days highlights the importance of close follow-up.

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.

Retrospective Validation of a Computerized Physiologic Equation to Predict Minute Ventilation Needs in Critically Ill Children.

OBJECTIVES: Mechanical ventilation (MV) is pervasive among critically ill children. We sought to validate a computerized physiologic equation to predict minute ventilation requirements in children and test its performance against clinician actions in an in silico trial. DESIGN: Retrospective, electronic medical record linkage, cohort study. SETTING: Quaternary PICU. PATIENTS: Patients undergoing invasive MV, serial arterial blood gas (ABG) analysis within 1-6 hours, and pharmacologic neuromuscular blockade (NMB). MEASUREMENTS AND MAIN RESULTS: ABG values were filtered to those occurring during periods of NMB. Simultaneous ABG and minute ventilation data were linked to predict serial Pa co2 and pH values using previously published physiologic equations. There were 15,121 included ABGs across 500 encounters among 484 patients, with a median (interquartile range [IQR]) of 20 (10-43) ABGs per encounter at a duration of 3.6 (2.1-4.2) hours. The median (IQR) Pa co2 prediction error was 0.00 (-3.07 to 3.00) mm Hg. In Bland-Altman analysis, the mean error was -0.10 mm Hg (95% CI, -0.21 to 0.01 mm Hg). A nested, in silico trial of ABGs meeting criteria for weaning (respiratory alkalosis) or escalation (respiratory acidosis), compared the performance of recommended ventilator changes versus clinician decisions. There were 1,499 of 15,121 ABGs (9.9%) among 278 of 644 (43.2%) encounters included in the trial. Calculated predictions were favorable to clinician actions in 1124 of 1499 ABGs (75.0%), equivalent to clinician choices in 26 of 1499 ABGs (1.7%), and worse than clinician decisions in 349 of 1499 ABGs (23.3%). Calculated recommendations were favorable to clinician decisions in sensitivity analyses limiting respiratory rate, analyzing only when clinicians made changes, excluding asthma, and excluding acute respiratory distress syndrome. CONCLUSIONS: A computerized equation to predict minute ventilation requirements outperformed clinicians' ventilator adjustments in 75% of ABGs from critically ill children in this retrospective analysis. Prospective validation studies are needed.

A Comparison of the Anticoagulation Efficacy and Safety of Epoprostenol to Heparin and Citrate in Children Receiving Continuous Renal Replacement Therapy.

INTRODUCTION: Anticoagulants are used in continuous renal replacement therapy (CRRT) to prolong filter life. There are no prior investigations directly comparing epoprostenol to more commonly used forms of anticoagulation in children. Therefore, the primary aim of this study was to assess the efficacy and safety of epoprostenol as compared to heparin and citrate anticoagulation in a pediatric cohort. METHODS: We performed a retrospective analysis of all patients <18 years of age admitted to an academic quaternary care children's hospital from 2017-2022 who received epoprostenol, heparin, or citrate exclusively for CRRT anticoagulation. Efficacy was evaluated by comparing the hours to the first unintended filter change and the ratio of filters used to CRRT days. Safety was assessed by evaluating changes in platelet count and vasoactive-ionotropic score (VIS). RESULTS: Of 101 patients, 44 received epoprostenol (43.6%), 38 received heparin (37.6%), and 19 received citrate (18.8%). The first filter change was more commonly planned in patients receiving anticoagulation with epoprostenol (43%) as compared to citrate (11%) or heparin (29%) (p = 0.034). Of those patients where the first filter change was unintended (n = 33), there were greater median hours until the filter was replaced in those receiving epoprostenol (29) when compared to citrate (21) (p = 0.002) or heparin (18) (p = 0.003). There was a smaller median ratio of filters used to days on therapy in the patients that received epoprostenol (0.53) when compared to citrate (1) (p = 0.003) or heparin (0.75) (p = 0.001). For those receiving epoprostenol, there was no significant decrease in platelet count when comparing values prior to CRRT initiation through 7 days of therapy. There was no significant difference in VIS when comparing values prior to CRRT initiation through the first 2 days of CRRT. CONCLUSIONS: Epoprostenol-based anticoagulation is effective when compared to other anticoagulation strategies used in pediatric CRRT with a favorable side effect profile.

Current practices in pediatric continuous kidney replacement therapy: a systematic review-guided multinational modified Delphi consensus study.

BACKGROUND: Continuous kidney replacement therapy (CKRT) has become an integral part of the care of critically ill children. However, uncertainty exists regarding the current state of how CKRT is prescribed and delivered in children. The main objective of this study was to identify the current practices for pediatric CKRT. METHODS: We conducted a systematic review of the literature from 2012 to 2022 to identify data regarding CKRT timing of initiation, dosing, anticoagulation, fluid removal, and quality monitoring. Using this data, we then performed a two-round modified Delphi process using a multinational internet-assisted survey of prescribers of CKRT. RESULTS: The survey was constructed using 172 articles that met inclusion criteria (12% of studies were pediatric focused). A total of 147 and 126 practitioners completed the survey in rounds 1 and 2, respectively. Participants represented Europe (9.5-11.6%) and North America including pediatric intensivists, nephrologists, and advance practice providers. Consensus (defined as a ≥ 75% participant response of "sometimes" or "always") was achieved for 26 statements. There was consensus in the practices of CKRT initiation, dosing, method of anticoagulation, and fluid removal. In contrast, there appears to be greater variability in the methods used for monitoring anticoagulation and the quality of the delivered treatment. CONCLUSIONS: Our study results suggest that the current state of pediatric CKRT practice is reflective of the literature over the last 10 years, which is largely based on the care of adult patients. This data provides a framework to study best practices to further improve outcomes for children receiving CKRT. A higher resolution version of the Graphical abstract is available as Supplementary information.

Effects of preoperative high-oral protein loading on short- and long-term renal outcomes following cardiac surgery: a cohort study.

BACKGROUND: Post-cardiac surgery acute kidney injury (AKI) is associated with increased mortality. A high-protein meal enhances the renal blood flow and glomerular filtration rate (GFR) and might protect the kidneys from acute ischemic insults. Hence, we assessed the effect of a preoperative high-oral protein load on post-cardiac surgery renal function and used experimental models to elucidate mechanisms by which protein might stimulate kidney-protective effects. METHODS: The prospective "Preoperative Renal Functional Reserve Predicts Risk of AKI after Cardiac Operation" study follow-up was extended to postoperative 12 months for 109 patients. A 1:2 ratio propensity score matching method was used to identify a control group (n = 214) to comparatively evaluate the effects of a preoperative protein load and standard care. The primary endpoints were AKI development and postoperative estimated GFR (eGFR) loss at 3 and 12 months. We also assessed the secretion of tissue inhibitor of metalloproteases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), biomarkers implicated in mediating kidney-protective mechanisms in human kidney tubular cells that we exposed to varying protein concentrations. RESULTS: The AKI rate did not differ between the protein loading and control groups (13.6 vs. 12.3%; p = 0.5). However, the mean eGFR loss was lower in the former after 3 months (0.1 [95% CI - 1.4, - 1.7] vs. - 3.3 [95% CI - 4.4, - 2.2] ml/min/1.73 m2) and 12 months (- 2.7 [95% CI - 4.2, - 1.2] vs - 10.2 [95% CI - 11.3, - 9.1] ml/min/1.73 m2; p < 0.001 for both). On stratification based on AKI development, the eGFR loss after 12 months was also found to be lower in the former (- 8.0 [95% CI - 14.1, - 1.9] vs. - 18.6 [95% CI - 23.3, - 14.0] ml/min/1.73 m2; p = 0.008). A dose-response analysis of the protein treatment of the primary human proximal and distal tubule epithelial cells in culture showed significantly increased IGFBP7 and TIMP-2 expression. CONCLUSIONS: A preoperative high-oral protein load did not reduce AKI development but was associated with greater renal function preservation in patients with and without AKI at 12 months post-cardiac surgery. The potential mechanisms of action by which protein loading may induce a kidney-protective response might include cell cycle inhibition of renal tubular epithelial cells. Clinical trial registration ClinicalTrials.gov: NCT03102541 (retrospectively registered on April 5, 2017) and ClinicalTrials.gov: NCT03092947 (retrospectively registered on March 28, 2017).