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Objectives: Continuous renal replacement therapy (CRRT) and shock are both associated with high morbidity and mortality in the ICU. Adult data suggest renoprotective effects of vasopressin vs. catecholamines (norepinephrine and epinephrine). We aimed to determine whether vasopressin use during CRRT was associated with improved kidney outcomes in children and young adults., Design: Secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), a multicenter, retrospective cohort study., Setting: Neonatal, cardiac, PICUs at 34 centers internationally from January 1, 2015, to December 31, 2021., Patients/subjects: Patients younger than 25 years receiving CRRT for acute kidney injury and/or fluid overload and requiring vasopressors. Patients receiving vasopressin were compared with patients receiving only norepinephrine/epinephrine. The impact of timing of vasopressin relative to CRRT start was assessed by categorizing patients as: early (on or before day 0), intermediate (days 1-2), and late (days 3-7)., Interventions: None., Measurements and Main Results: Of 1016 patients, 665 (65%) required vasopressors in the first week of CRRT. Of 665, 248 (37%) received vasopressin, 473 (71%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (death, renal replacement therapy dependence, and/or > 125% increase in serum creatinine from baseline 90 days from CRRT initiation), and 195 (29%) liberated from CRRT on the first attempt within 28 days. Receipt of vasopressin was associated with higher odds of MAKE-90 (adjusted odds ratio [aOR], 1.80; 95% CI, 1.20-2.71; p = 0.005) but not liberation success. In the vasopressin group, intermediate/late initiation was associated with higher odds of MAKE-90 (aOR, 2.67; 95% CI, 1.17-6.11; p = 0.02) compared with early initiation., Conclusions: Nearly two-thirds of children and young adults receiving CRRT required vasopressors, including over one-third who received vasopressin. Receipt of vasopressin was associated with more MAKE-90, although earlier initiation in those who received it appears beneficial. Prospective studies are needed to understand the appropriate timing, dose, and subpopulation for use of vasopressin., Competing Interests: Dr. Stanski received funding from the National Institute of General Medical Sciences (K23GM151444-01). Dr. Gist is a consultant for BioPorto Diagnostics and Potrero Medical; she received funding from the Gerber Foundation. Dr. Stenson received funding from the National Institute of Child Health and Development (K12HD047349). Dr. Ollberding serves as a consultant for SeaStar Medical. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

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., Competing Interests: Declarations. Conflict of interest: All authors declare no real or perceived conflicts of interest that could affect the study design, collection, analysis and interpretation of data, writing of the report, or the decision to submit for publication. For full disclosure, we provide here an additional list of other authors’ commitments and funding sources that are not directly related to this study: Katja Gist is a consultant for Bioporto Diagnostics and Potrero Medical. Shina Menon is a consultant for Medtronic, Inc. and Nuwellis, Inc. Theresa A. Mottes is a consultant for Medtronic Inc. Melissa Muff-Luett is a consultant for Medtronic Inc. Michael Zappitelli has completed consultant work for Bioporto Diagnostics Inc. No other competing interests were reported., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Postoperative acute kidney injury (PO-AKI) is a frequent complication after surgery. Various tools have been proposed to identify patients at high risk for AKI, including preoperative serum creatinine or estimated glomerular filtration rate (eGFR), urinary cell cycle arrest, and tubular damage biomarkers; however, none of these can appropriately assess AKI risk before surgery. Renal functional reserve (RFR) screened by the Doppler-derived intraparenchymal renal resistive index variation (IRRIV) test has been proposed to identify patients at risk for AKI before a kidney insult. IRRIV test has been developed in healthy individuals and previously investigated in cardiac surgery patients. This study aims to evaluate the value of the IRRIV test in identifying PO-AKI among patients undergoing robotic abdominal surgery in the Trendelenburg position for pelvic oncological disease., Methods: We performed a prospective, double-blinded, observational study. Preoperative baseline renal function and RFR were assessed in 53 patients with baseline eGFR >60 mL/min/1.73 m2, undergoing robotic surgery in the Trendelenburg position for pelvic oncological disease. The capability of Doppler-derived RFR in predicting PO-AKI was investigated with the area under the receiver operating characteristic curve (ROC-AUC)., Results: Approximately 15.1% of patients developed AKI within the first 3 postoperative days. Thirty-one (58.5%) patients had a physiologic delta-RRI (ie, ≥0.05), while 22 (41.5%) patients did not. The ROC-AUC for PO-AKI was 0.85 (95% confidence interval [CI], 0.74-0.97; P = .007) for serum creatinine, 0.84 (95% CI, 0.71-0.96; P = .006) for eGFR, and 0.84 (95% CI, 0.78-0.91; P = .017) for delta-RRI. When combined with eGFR, the ROC-AUC for delta-RRI was 0.95 (95% CI, 0.9-1)., Conclusions: Our findings show that the preoperative assessment of Doppler-derived RFR combined with baseline renal function improves the capability of identifying patients at high risk for PO-AKI with eGFR >60 mL/min/1.73 m2 after robotic abdominal surgery in Trendelenburg position for pelvic oncological disease., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

Purpose: Continuous renal replacement therapy (CRRT) is used for supportive management of acute kidney injury (AKI) and disorders of fluid balance (FB). Little is known about the predictors of successful liberation in children and young adults. We aimed to identify the factors associated with successful CRRT liberation., Methods: The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease study is an international multicenter retrospective study (32 centers, 7 nations) conducted from 2015 to 2021 in children and young adults (aged 0-25 years) treated with CRRT for AKI or FB disorders. Patients with previous dialysis dependence, tandem extracorporeal membrane oxygenation use, died within the first 72 h of CRRT initiation, and those who never had liberation attempted were excluded. Patients were categorized based on first liberation attempt: reinstituted (resumption of any dialysis within 72 h) vs. success (no receipt of dialysis for ≥ 72 h). Multivariable logistic regression was used to identify factors associated with successful CRRT liberation., Results: A total of 622 patients were included: 287 (46%) had CRRT reinstituted and 335 (54%) were successfully liberated. After adjusting for sepsis at admission and illness severity parameters, several factors were associated with successful liberation, including higher VIS (vasoactive-inotropic score) at CRRT initiation (odds ratio [OR] 1.35 [1.12-1.63]), higher PELOD-2 (pediatric logistic organ dysfunction-2) score at CRRT initiation (OR 1.71 [1.24-2.35]), higher urine output prior to CRRT initiation (OR 1.15 [1.001-1.32]), and shorter CRRT duration (OR 0.19 [0.12-0.28])., Conclusions: Inability to liberate from CRRT was common in this multinational retrospective study. Modifiable and non-modifiable factors were associated with successful liberation. These results may inform the design of future clinical trials to optimize likelihood of CRRT liberation success., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2023. The Author(s).)

Background: The impact of disorders of fluid balance, including the pathologic state of fluid overload in sick children has become increasingly apparent. With this understanding, there has been a shift from application of absolute thresholds of fluid accumulation to an appreciation of the intricacies of fluid balance, including the impact of timing, trajectory, and disease pathophysiology., Methods: The 26th Acute Disease Quality Initiative was the first to be exclusively dedicated to pediatric and neonatal acute kidney injury (pADQI). As part of the consensus panel, a multidisciplinary working group dedicated to fluid balance, fluid accumulation, and fluid overload was created. Through a search, review, and appraisal of the literature, summative consensus statements, along with identification of knowledge gaps and recommendations for clinical practice and research were developed., Conclusions: The 26th pADQI conference proposed harmonized terminology for fluid balance and for describing a pathologic state of fluid overload for clinical practice and research. Recommendations include that the terms daily fluid balance, cumulative fluid balance, and percent cumulative fluid balance be utilized to describe the fluid status of sick children. The term fluid overload is to be preserved for describing a pathologic state of positive fluid balance associated with adverse events. Several recommendations for research were proposed including focused validation of the definition of fluid balance, fluid overload, and proposed methodologic approaches and endpoints for clinical trials., (© 2023. The Author(s).)

Importance: Continuous kidney replacement therapy (CKRT) is increasingly used in youths with critical illness, but little is known about longer-term outcomes, such as persistent kidney dysfunction, continued need for dialysis, or death., Objective: To characterize the incidence and risk factors, including liberation patterns, associated with major adverse kidney events 90 days after CKRT initiation (MAKE-90) in children, adolescents, and young adults., Design, Setting, and Participants: This international, multicenter cohort study was conducted among patients aged 0 to 25 years from The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry treated with CKRT for acute kidney injury or fluid overload from 2015 to 2021. Exclusion criteria were dialysis dependence, concurrent extracorporeal membrane oxygenation use, or receipt of CKRT for a different indication. Data were analyzed from May 2 to December 14, 2023., Exposure: Patient clinical characteristics and CKRT parameters were assessed. CKRT liberation was classified as successful, reinstituted, or not attempted. Successful liberation was defined as the first attempt at CKRT liberation resulting in 72 hours or more without return to dialysis within 28 days of CKRT initiation., Main Outcomes and Measures: MAKE-90, including death or persistent kidney dysfunction (dialysis dependence or ≥25% decline in estimated glomerular filtration rate from baseline), were assessed., Results: Among 969 patients treated with CKRT (529 males [54.6%]; median [IQR] age, 8.8 [1.7-15.0] years), 630 patients (65.0%) developed MAKE-90. On multivariable analysis, cardiac comorbidity (adjusted odds ratio [aOR], 1.60; 95% CI, 1.08-2.37), longer duration of intensive care unit admission before CKRT initiation (aOR for 6 days vs 1 day, 1.07; 95% CI, 1.02-1.13), and liberation pattern were associated with MAKE-90. In this analysis, patients who successfully liberated from CKRT within 28 days had lower odds of MAKE-90 compared with patients in whom liberation was attempted and failed (aOR, 0.32; 95% CI, 0.22-0.48) and patients without a liberation attempt (aOR, 0.02; 95% CI, 0.01-0.04)., Conclusions and Relevance: In this study, MAKE-90 occurred in almost two-thirds of the population and patient-level risk factors associated with MAKE-90 included cardiac comorbidity, time to CKRT initiation, and liberation patterns. These findings highlight the high incidence of adverse outcomes in this population and suggest that future prospective studies are needed to better understand liberation patterns and practices.

Introduction: Continuous renal replacement therapies (CRRTs) require constant monitoring and periodic treatment readjustments, being applied to highly complex patients, with rapidly changing clinical needs. To promote precision medicine in the field of renal replacement therapy and encourage dynamic prescription, the Acute Dialysis Quality Initiative (ADQI) recommends periodically measuring the solutes extracorporeal clearance with the aim of assessing the current treatment delivery and the gap from the therapeutic prescription (often intended as effluent dose). To perform this procedure, it is therefore necessary to obtain blood and effluent samples from the extracorporeal circuit to measure the concentrations of a target solute (usually represented by urea) in prefilter, postfilter, and effluent lines. However, samples must be collected simultaneously from the extracorporeal circuit ports, with the same suction flow at an unknown rate., Methods: The proposed study takes the first step toward identifying the technical factors that should be considered in determining the optimal suction rate to collect samples from the extracorporeal circuit to measure the extracorporeal clearance for a specific solute., Results: The results obtained identify the low suction rate (i.e., 1 mL/min) as an ideal parameter for an adequate sampling method. Low velocities do not perturb the external circulation system and ensure stability prevailing pressures in the circuit. Higher velocities can be performed only with blood flows above 120 mL/min preferably in conditions of appropriate filtration fraction., Discussion/conclusions: The specific value of aspiration flow rate must be proportioned to the prescription of CRRT treatments set by the clinician., (© 2023 S. Karger AG, Basel.)

Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Here we provide graded recommendations for managing SA-AKI and highlight priorities for future research., (© 2023. Springer Nature Limited.)

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., Competing Interests: Drs. Soranno and Akcan-Arikan received support for article research from the National Institutes of Health (NIH). All authors declare no real or perceived conflicts of interest that could affect the study design, collection, analysis and interpretation of data, writing of the report, or the decision to submit for publication. For full disclosure, we provide here an additional list of other author’s commitments and funding sources that are not directly related to this study: Dr. Askenazi is a consultant for Baxter, Nuwellis, Medtronic Bioporto, and Seastar. Dr. Askenazi receives grant funding for education and research that is not related to this project from the NIH, Baxter, Nuwellis, Medtronic, Seastar, and Bioporto; he disclosed that he is the founder and Chief Scientific Officer of Zorroflow Inc. Dr. Selewski’s institution received funding from Travere. Drs. Selewski, Basu, and Zappitelli received funding from Bioporto. Dr. Gist is a consultant for Bioporto and Potrero Medical. Dr. Basu received funding from Potrero Medical. Dr. Zappitelli received funding from Baxter. Dr. Akcan-Arikan’s institution received funding from Bioporto and the National Institute of Allergy and Infectious Diseases. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose of Review: The issues of fluid balance and fluid overload are currently considered crucial aspects of pediatric critically ill patients' care., Recent Findings: This review describes current understanding of fluid management in critically ill children in terms of fluid balance and fluid overload and its effects on patients' outcomes. The review describes current evidence surrounding definitions, monitoring, and treatment of positive fluid balance. In particular, the review focuses on specific patient conditions, including perioperative cardiac surgery, severe acute respiratory failure, and extracorporeal membrane oxygenation therapy, as the ones at highest risk of developing fluid overload and poor clinical outcomes. Gaps in understanding include specific thresholds at which fluid overload occurs in all critically ill children or specific populations and optimal timing of decongestion of positive fluid balance., Summary: Current evidence on fluid balance in critically ill children is mainly based on retrospective and observational studies, and intense research should be recommended in this important field. In theory, active decongestion of patients with fluid overload could improve mortality and other clinical outcomes, but randomized trials or advanced pragmatic studies are needed to better understand the optimal timing, patient characteristics, and tools to achieve this., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Objectives: Multisystem inflammatory syndrome in children (MIS-C) manifests with heart dysfunction and respiratory failure some weeks after a severe acute respiratory syndrome coronavirus disease 2 infection. The aim of our study was to explore the prevalence, severity, timing, and duration of acute kidney injury (AKI) in MIS-C patients. Furthermore, we evaluated which clinical variables and outcomes are associated with AKI., Design: Multicenter retrospective study., Setting: Five tertiary hospital PICUs in Italy. Data were collected in the first 7 days of PICU admission and renal function was followed throughout the hospital stay., Patients: Patients less than 18 years old admitted to the PICU for greater than 24 hours with MIS-C., Interventions: None., Measurements and Main Results: We collected the following data, including: demographic information, inflammatory biomarkers, lactate levels, Pa o2 /F io2 , ejection fraction, N-terminal pro-B-type natriuretic peptide (NT-proBNP), renal function (serum creatinine, urinary output, fluid balance, and percentage fluid accumulation), Vasoactive-Inotropic Score (VIS), pediatric Sequential Organ Failure Assessment (pSOFA), and Pediatric Index of Mortality 3. AKI was diagnosed in eight of 38 patients (21%) and severe AKI was present in four of eight patients. In all cases, AKI was present at PICU admission and its median (interquartile range) duration was 3.5 days (1.5-5.7 d). We did not identify differences between AKI and no-AKI patients when not making correction for multiple comparisons, for example, in weight, ejection fraction, pSOFA, Pa o2 /F io2 , and lactates. We failed to identify any difference in these groups in urine output and fluid balance. Exploratory analyses of serial data between no-AKI and AKI patients showed significant differences on lymphocyte count, NT-proBNP value, ejection fraction, pSOFA, Pa o2 /F io2 , and VIS., Conclusions: In this multicenter Italian PICU experience, MIS-C is associated with AKI in one-in-five cases. In general, AKI is characterized by an associated reduction in glomerular filtration rate with a self-limiting time course., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: The most severely ill neonates and infants with AKI who need kidney replacement therapy have had to rely upon peritoneal dialysis, or adaptations of veno-venous continuous kidney replacement therapy (CKRT) devices for adults. Data from the Prospective Pediatric CRRT (ppCRRT) registry observed children < 10 kg had a lower survival rate than children > 10 kg (44% vs. 64%, p < 0.001). A CKRT device designed specifically for small children could improve outcomes. The Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM™) is specifically dedicated to providing CKRT for newborns and small infants., Methods: We performed a retrospective cohort analysis comparing patient severity of illness and outcomes between the ppCRRT and CARPEDIEM registries, involving 6 Italian pediatric intensive care units. Thirty-eight subjects from the CARPEDIEM registry and 84 subjects from the ppCRRT registry < 10 kg were screened for comparison. We compared patient outcomes with a weight-matched cohort (< 5 kg) of 34 patients from the CARPEDIEM registry and 48 patients from the ppCRRT registry., Results: The ppCRRT subjects had higher rates of vasoactive medication at CKRT initiation. Survival to CKRT termination was higher for CARPEDIEM subjects (33/34 vs. 21/48, p < 0.0001). Multivariable logistic regression showed that CARPEDIEM registry cohort was the only variable to retain an association with survival to CKRT discontinuation., Conclusions: We suggest children receiving CKRT using CARPEDIEM have excellent survival. Our data should be interpreted with caution given the retrospective comparison across two eras more than a decade apart., (© 2021. IPNA.)

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.

Objectives: To describe the incidence, associated characteristics, and outcomes of the maximum severity of acute kidney injury (AKI) in a heterogeneous population of critically ill children with cardiac disease., Design: Retrospective cohort study., Setting: Pediatric cardiac intensive care unit (PCICU)., Participants: Patients admitted to the PCICU., Interventions: None., Measurements and Main Results: From January 2018 to July 2020 all patients admitted to a tertiary PCICU were included. Only the first admission was considered. Neonates ≤seven days old were excluded. Of 742 patients, 53 were medical cases, 69 catheterization laboratory cases, and 620 surgical cases (with five subgroups). The median age was 2.47 years (interquartile range [IQR], 0.38-9.85 years), with a median Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score of 2 (IQR, 1-3). Median PCICU length of stay was three days (IQR, 2-7 days), and 21 (2.8%) patients died. Any incidence of AKI occurred in 70% of patients, 26% of which were classified as mild (stage 1) and 43% as severe (stages 2 and 3). AKI was diagnosed by urine output criteria in 56%, serum creatinine in 28%, and both in 16% of patients. Severe AKI occurred in subgroups as follows: medical (38%), catheterization laboratory (45%), correction (35%), palliation (55%), transplantation (85%), mechanical assistance (70%), and redo surgery (58%). Severe AKI patients were significantly older (p = 0.004), had a higher Pediatric Index of Mortality 3 score (p = 0.0004), had a higher cumulative fluid balance (p < 0.0001), and had a longer cardiopulmonary bypass time (p < 0.0001). Early AKI (≤24 hours from admission) was the most frequent presentation, with a greater proportion of severe cases in the early group compared with the intermediate (>24 and ≤48 hours) and late (>48 hours) (p < 0.0001) groups. Presentation of late severe AKI had a higher mortality (odds ratio, 4.9; 95% confidence interval, 1.8-15; p = 0.001)., Conclusions: Severe AKI occurs in 43% of cardiac children and is diagnosed early, most often by urine output criteria. Severe AKI incidence varies significantly within subgroups of cardiac patients. Late AKI is associated with worse outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Children seem to be less severely affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as compared to adults. Little is known about the prevalence and pathogenesis of acute kidney injury (AKI) in children affected by SARS-CoV-2. Dehydration seems to be the most common trigger factor, and meticulous attention to fluid status is imperative. The principles of initiation, prescription, and complications related to renal replacement therapy are the same for coronavirus disease (COVID) patients as for non-COVID patients. Continuous renal replacement therapy (CRRT) remains the most common modality of treatment. When to initiate and what modality to use are dependent on the available resources. Though children are less often and less severely affected, diversion of all hospital resources to manage the adult surge might lead to limited CRRT resources. We describe how these shortages might be mitigated. Where machines are limited, one CRRT machine can be used for multiple patients, providing a limited number of hours of CRRT per day. In this case, increased exchange rates can be used to compensate for the decreased duration of CRRT. If consumables are limited, lower doses of CRRT (15-20 mL/kg/h) for 24 h may be feasible. Hypercoagulability leading to frequent filter clotting is an important issue in these children. Increased doses of unfractionated heparin, combination of heparin and regional citrate anticoagulation, or combination of prostacyclin and heparin might be used. If infusion pumps to deliver anticoagulants are limited, the administration of low-molecular-weight heparin might be considered. Alternatively in children, acute peritoneal dialysis can successfully control both fluid and metabolic disturbances. Intermittent hemodialysis can also be used in patients who are hemodynamically stable. The keys to successfully managing pediatric AKI in a pandemic are flexible use of resources, good understanding of dialysis techniques, and teamwork., (© 2020 S. Karger AG, Basel.)

Purpose of Review: This article reviews the current evidence supporting the use of precision medicine in the delivery of acute renal replacement therapy (RRT) to critically ill patients, focusing on timing, solute control, anticoagulation and technologic innovation., Recent Findings: Precision medicine is most applicable to the timing of RRT in critically ill patients. As recent randomized controlled trials have failed to provide consensus on when to initiate acute RRT, the decision to start acute RRT should be based on individual patient clinical characteristics (e.g. severity of the disease, evolution of clinical parameters) and logistic considerations (e.g. organizational issues, availability of machines and disposables). The delivery of a dynamic dialytic dose is another application of precision medicine, as patients may require different and varying dialysis doses depending on individual patient factors and clinical course. Although regional citrate anticoagulation (RCA) is recommended as first-line anticoagulation for continuous RRT, modifications to RCA protocols and consideration of other anticoagulants should be individualized to the patient's clinical condition. Finally, the evolution of RRT technology has improved precision in dialysis delivery through increased machine accuracy, connectivity to the electronic medical record and automated reduction of downtime., Summary: RRT has become a complex treatment for critically ill patients, which allows for the prescription to be precisely tailored to the different clinical requirements.

Importance: In the last decade, new biomarkers for acute kidney injury (AKI) have been identified and studied in clinical trials. Guidance is needed regarding how best to incorporate them into clinical practice., Objective: To develop recommendations on AKI biomarkers based on existing data and expert consensus for practicing clinicians and researchers., Evidence Review: At the 23rd Acute Disease Quality Initiative meeting, a meeting of 23 international experts in critical care, nephrology, and related specialties, the panel focused on 4 broad areas, as follows: (1) AKI risk assessment; (2) AKI prediction and prevention; (3) AKI diagnosis, etiology, and management; and (4) AKI progression and kidney recovery. A literature search revealed more than 65 000 articles published between 1965 and May 2019. In a modified Delphi process, recommendations and consensus statements were developed based on existing data, with 90% agreement among panel members required for final adoption. Recommendations were graded using the Grading of Recommendations, Assessment, Development and Evaluations system., Findings: The panel developed 11 consensus statements for biomarker use and 14 research recommendations. The key suggestions were that a combination of damage and functional biomarkers, along with clinical information, be used to identify high-risk patient groups, improve the diagnostic accuracy of AKI, improve processes of care, and assist the management of AKI., Conclusions and Relevance: Current evidence from clinical studies supports the use of new biomarkers in prevention and management of AKI. Substantial gaps in knowledge remain, and more research is necessary.

Background: Providing extracorporeal renal support to neonates and infants involves a number of technical and clinical issues, possibly discouraging early utilization. This report aims to describe a multicenter experience of continuous kidney replacement therapy (CKRT) delivery to small infants using a device specifically designed for this age group., Methods: A retrospective cohort analysis of all patients treated with the Carpediem™ machine (Bellco-Medtronic, Mirandola, Italy) in 6 centers between June 2013 and December 2016., Results: Twenty-six neonates and small infants received 165 CKRT sessions in convective modality. Median age at neonatal intensive care unit admission 1 day (IQR 1-11), median body weight 2.9 kg (IQR 2.2-3.6). Median circuit duration 14 h (IQR 10-22), with delivered/prescribed time ratio of 84%. CKRT was conducted using 4 Fr (27%), 5 Fr (35%), 6.5 Fr (11%), and 7 Fr (3%) vascular access, and with umbilical and peripheral accesses (11% each) allowing overall median blood flow of 4.5 ml/kg/min (IQR 3.4-6) and median effluent flow rate 35 ml/kg/h (IQR 28-42). Circuits were primed with normal saline in 58% of treatments, colloids in 31%, and packed red blood cells in 11%. No serious adverse events directly related to machine application were reported by any center. Twenty-five (96%) patients survived their CKRT course and 13 patients (50%) survived to ICU discharge., Conclusions: CKRT in neonates was easy to initiate and conduct when performed with small central vascular accesses coupled with this device. A dedicated technology for infant CKRT delivery enables patients to be safely treated avoiding technical complications. Graphical abstract.

Background: Multi-organ dysfunction in critical illness is common and frequently involves the lungs and kidneys, often requiring organ support such as invasive mechanical ventilation (IMV), renal replacement therapy (RRT) and/or extracorporeal membrane oxygenation (ECMO)., Methods: A consensus conference on the spectrum of lung-kidney interactions in critical illness was held under the auspices of the Acute Disease Quality Initiative (ADQI) in Innsbruck, Austria, in June 2018. Through review and critical appraisal of the available evidence, the current state of research, and both clinical and research recommendations were described on the following topics: epidemiology, pathophysiology and strategies to mitigate pulmonary dysfunction among patients with acute kidney injury and/or kidney dysfunction among patients with acute respiratory failure/acute respiratory distress syndrome. Furthermore, emphasis was put on patients receiving organ support (RRT, IMV and/or ECMO) and its impact on lung and kidney function., Conclusion: The ADQI 21 conference found significant knowledge gaps about organ crosstalk between lung and kidney and its relevance for critically ill patients. Lung protective ventilation, conservative fluid management and early recognition and treatment of pulmonary infections were the only clinical recommendations with higher quality of evidence. Recommendations for research were formulated, targeting lung-kidney interactions to improve care processes and outcomes in critical illness.

Objectives: Renal replacement therapy in infants and small children is the treatment of choice for severe oligoanuric renal dysfunction, with an increasing consensus that early initiation might contribute to preventing acute kidney injury complications. Safer renal replacement therapy devices specifically designed for neonates may contribute to ameliorating outcomes and increasing chances of survival. One of the crucial factors to achieve an effective renal replacement therapy in small infants is adequate vascular access. The interaction of small size central vascular catheters with renal replacement therapy devices has never been investigated. The aim of this study was to characterize both the operating conditions and performance of three different central vascular catheters sizes (4F, 5F, and 7F) connected to two different extracorporeal blood circulation models (adult and pediatric). The rheologic performance of each vascular access size in combination with the adult and pediatric renal replacement therapy models was described., Design: Series of experimental extracorporeal circulation circuit tests were conducted with different setups. A two-roller pump was used to simulate a standard adult dialysis machine, whereas a small three-roller pump served as pediatric renal replacement therapy device., Setting: A pressure-flow setup aimed to collect pressure and flow values under different test conditions. A second experiment focused on hemolysis estimation induced by the extracorporeal system. Hemolysis exclusively induced by the 4F catheter was also evaluated. Finally, our data were applied to estimate the optimal catheter size theoretically capable of delivering adequate doses basing on anthropometric data (patient weight and cannulation site) in absence of direct ultrasound vessel measurement., Subjects: In vitro tests conducted on simulated extracorporeal circuit models of continuous pediatric and neonatal renal replacement therapy., Interventions: None., Measurements and Main Results: When 4F and 5F catheters are used, maximal blood flows within safe circuit pressures can be set at the values of 13 and 29 mL/min, respectively, when a small pump is used. Differently, when using adult roller pumps, only maximal flows of 10 and 20 mL/min are reached. However, hemolysis is higher when using a three-roller pump compared with the two-roller. The clinical impact of this increased hemolytic burden is likely not relevant., Conclusions: Small size central vascular catheters display optimal rheologic performances in terms of pressures and flows particularly when the renal replacement therapy device is equipped with pumps proportional to central vascular catheters sizes, and even when relatively high blood flows are set. This is achieved at the risk of a higher hemolysis rate.

Introduction: Definition, prevention, and management of acute kidney injury (AKI) and the optimal prescription and delivery of renal replacement therapy (RRT) are currently matters of ongoing discussion. Due to the lack of definitive published literature, a wide gap might exist between routine clinical practice and available recommendations. The aim of this survey was to explore the clinical approach to AKI and RRT in a broad population of nephrologists and intensivists participating in the 36th International course on AKI and Continuous RRT (CRRT), held in Vicenza in June 2018. The responses of the 369 participants to a questionnaire on several aspects of critical care nephrology were analyzed and detailed., Results: Approximately 450 participants attended the course; of these, 369 (82%) correctly filled the survey forms. According to the reported answers, the average incidence of AKI in respondents' intensive care units (ICU) was 26.8% (SD ±15.99) and AKI requiring dialysis was 13% (SD ±29.7). Sixty-four percent of participants defined AKI as an increase in serum creatinine (SCr) up to 0.99 mg/dL (SD ±0.88 mg/dL); 2.4% defined AKI as an increase in urea nitrogen up to 83.6 mg/dL (SD ±36.6 mg/dL); 33.6% defined AKI as decreased urine output to less than 1 mL/kg/h (SD ±0.6 mL/kg/h). The most common answer to classify AKI was Kidney Disease: Improving Global Outcomes (KDIGO; 41%) criteria. Most of the participants (25%) think novel biomarkers should replace SCr on daily routine laboratory screening, and Cystatin C was the most commonly used biomarker (19%). The use of diuretics in AKI patients was high (62%). Continuous RRT (59%) and heparin anticoagulation (42%) appeared to be the most common approaches in ICU., Conclusions: KDIGO appeared to be widely applied. The use of novel biomarkers has also emerged in recent years even if some consistent cost-benefit evidence is still lacking. There is a trend of increased awareness about AKI and extracorporeal treatments seem to be increasingly applied, when compared to previous surveys. Educational efforts and AKI management standardization still appear to be a fundamental aspect to harmonize therapeutic approaches and improve patients' outcomes., (© 2018 S. Karger AG, Basel.)

Background: ACUsmart (Medica S.P.A., Italy) is a new-generation, continuous renal replacement therapy (CRRT) machine for critically ill patients with acute kidney injury. We designed a multicenter international pilot study to provide a description of outlines of the ACUsmart system, evaluation aspects of functionality, usability, and feasibility, discriminating reasons of possible treatment's withdrawals or discontinuations and highlighting strong and weak points of the machine., Methods: Data of 23 CRRT (and 11 plasma exchange) treatments were collected from 4 intensive care units. Parameters such as treatment duration, downtime, delivered dose, and number and type of alarms were recorded. The general perception of the machine was quantified through the administration of a survey to each component of the evaluating staff., Results: A total treatment time of 447 h was carried with ACUsmart. Eleven continuous veno-venous hemofiltration, 4 continuous veno-venous hemodialysis , and 8 continuous veno-venous hemodiafiltration were performed. The average percentage of net treatment duration with respect to total treatment duration was 92.37%. The mean prescribed dose and delivered dose were 26.33 and 24.10 mL/kg/h, respectively. In general, the machine was rated by users involved as practical and easy to use, although few components need to be slightly improved., Conclusion: ACUsmart is a new multifunctional machine that meets most of the features required in a fourth-generation CRRT equipment., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Purpose of Review: Sepsis-induced acute kidney injury (SI-AKI) represents the first cause of AKI in ICUs, and renal replacement therapy (RRT) is frequently applied in advanced AKI stages. The debate between 'rescue' indications for RRT start in patients with severe AKI (acidosis, hyperkalemia, uremia, oliguria/anuria, volume overload) and a proactive RRT initiation is still ongoing. In addition, current SI-AKI pathophysiologic theory has identified the toxic effects of soluble middle-molecules released during sepsis and inflammation (pathogen and damaged associated molecular patterns).The purpose of the present review is to summarize the recent literature on RRT for patients with SI-AKI. Supportive or replacement measures for severe stages of renal dysfunction and blood purification techniques for sepsis syndrome will be reviewed., Recent Findings: Anticipated RRT for SI-AKI does not seem to improve survival or renal recovery. There is no clinical advantage by delivering continuous RRT at high doses for blood purification purposes. Similarly, specific applications with dedicated devices and membranes have yielded no clinical benefit in these patients, so far., Summary: In the present review, the recent insights and results from large randomized and nonrandomized trials in the area of RRT applied both as supportive measures for kidney failure and blood purification techniques are described.

The complex nature of single organ failure potentially leading to multiple organ dysfunction syndrome (MODS) in critically ill patients necessitates integrated supportive therapy. Rather than a primary disease, acute kidney injury (AKI) is considered a window to a potentially serious underlying systemic disease, which may partially explain the high morbidity and mortality rates associated with the condition. Renal replacement therapy (RRT) has been routinely used for more than a decade in various intensive care settings and there has also been an increase in the use of extracorporeal membrane oxygenation and extracorporeal carbon dioxide removal. When these renal and cardiopulmonary modalities are used together, a multidisciplinary approach is necessary to minimize negative interactions and unwanted adverse effects. In this review, we describe the patterns of organ crosstalk between the native and artificial organs, the incidence of AKI and need for RRT and associated mortality after extracorporeal organ support (ECOS) therapy, including the potential short- and long-term advantages and disadvantages of organ support in terms of renal function. We also review potential indications of RRT outside its conventional indications in patients with MODS, as well as technical considerations when RRT is used alongside other organ support therapies. Overall, available literature has not definitely established the ideal timing of these interventions, and whether early implementation impacts organ recovery and optimizes resource utilization is still a matter of open debate: it is possible that future research will be devoted to identify patient groups that may benefit from short- and long-term multiple organ support.

Background: Acute kidney injury (AKI) is a frequent complication of both cardiac and major non-cardiac surgery. AKI is independently associated with morbidity, mortality, and long-term adverse events including chronic kidney disease in postsurgical patients. Since specific treatment options for kidney failure are very limited, early identification, diagnosis, and renal support strategies are key steps to improve patients' outcome., Summary: According to current Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, AKI diagnosis is based on 2 functional markers, serum creatinine increase and urine output decrease, that are not renal-specific and have important limitations. However, preoperative risk stratification for postoperative AKI and/or early diagnosis after surgery could be the best way to apply preventive or timely supportive therapeutic measures. Clinical prediction scores, renal functional reserve assessment, and new biomarkers of kidney stress (suppression of tumorigenicity-2, insulin-like growth factor binding protein-7, tissue inhibitor metalloproteinase-2) may help the clinicians to identify patients at risk of AKI and that could benefit from the application of nephroprotective bundles suggested by the KDIGO guidelines. In severe AKI patients with oligoanuria and fluid accumulation, renal replacement therapy is the only supportive measure even if mode and timing remain open to investigation. Key messages: Perioperative AKI is an important and underdiagnosed complication. Identifying patients at high risk of AKI and diagnosing AKI early are major goals. Preventive interventions are mainly based on the KDIGO guidelines and bundles. Furthermore, a personalized multidisciplinary approach should always be considered to minimize the progression of disease and the complications related to kidney damage., (© 2018 S. Karger AG, Basel.)

Background: Acute kidney injury (AKI) in children is a serious condition with an important impact on morbidity and mortality. Onset can be insidious and it is frequently unrecognized in the early phase when the therapeutic opportunities are theoretically more effective., Summary: The present review focuses on the most recent epidemiology studies and the progress in pediatric AKI (pAKI) research. Standardization of definition (presented in the Kidney Disease: Improving Global Outcomes) and novel biomarkers have been developed to help clinicians recognize kidney injury in a timely manner, both in adult and pediatric populations. Strengths and weaknesses of these diagnostic tools are discussed and the clinical scoring system (Renal Angina Index), which aims to provide a rational context for biomarker utilization, is also presented. Even if effective treatments are not currently available for established AKI, specific preventive approaches and some promising pharmacological treatments will be detailed. Renal replacement therapy is currently considered the most effective way to manage fluid balance when severe AKI occurs. Key Messages: Great efforts in pAKI research have today led to new strategies for early AKI detection and prevention strategies. Further studies have to be conducted in the next future in order to definitely improve the outcomes of pediatric patients experiencing this deadly syndrome., (© 2018 S. Karger AG, Basel.)

Background: The acute reduction of kidney function in critically and noncritically ill patients (regardless of their age) is one of the deadliest clinical conditions ever reported in modern medicine. Acute kidney injury (AKI) symptoms are sneaky and potentially difficult to be identified at the right time at the bedside. One of the greatest efforts of the recent history of critical care nephrology has been to find a common classification for AKI definition and staging with the purpose of allowing a timely diagnosis and push forward epidemiologic research., Summary: AKI is currently defined by the Kidney Disease Improving Global Outcomes (KDIGO) consensus classification that applies conventional serum creatinine and urine output (UO) criteria. According to a recent large epidemiologic study, this classification led to the confirmation that AKI occurs in about half of adult critically ill patients admitted to the intensive care unit and that a stepwise increase in mortality is associated with the severity of AKI along KDIGO stages. Both serum creatinine and UO have inherent limitations in accurately diagnosing abrupt decreases of renal function, but their common and easy application in routine clinical practice is currently considered the standard of care for AKI diagnosis. Pediatric and neonatal AKI have recently been described and specific staging with KDIGO modification has been proposed. Key Messages: AKI is frequent in critically ill patients and significantly affects intensive outcomes independent of other clinical factors. AKI can be diagnosed and its severity accurately staged by the KDIGO classification and its modification for pediatric patients. Serum creatinine and UO criteria are applied in order to diagnose and stage AKI. Despite some significant limitations of these commonly applied biomarkers, their application has made it possible to clearly appraise the importance of accurate AKI identification in clinical practice in several studies for prognostic and therapeutic purposes., (© 2018 S. Karger AG, Basel.)

Innovation in continuous renal replacement therapies (CRRT) utilized to treat acute kidney injury (AKI) and sepsis, has brought new machines and techniques. Part of these new advances are due to the availability of innovative biomaterials and the construction of membranes with larger pores and wide distribution of pore sizes. This includes the creation of a new generation of high cut-off membranes whose utilization in clinical practice is promising for the wide spectrum of solutes that are removed during extracorporeal therapies.However, the enlargement of pore diameters brings some loss of albumin during treatment and this effect is still under evaluation, since there is a possibility that this is detrimental for the patient. A thorough review of the available clinical literature is reported in this paper with a reappraisal of the potential application of these new technologies.

Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious clinical disorder in the intensive care unit (ICU), occurring in a significant proportion of critically ill patients. However, many questions remain about the optimal administration of RRT with regard to several important considerations, including treatment dose, timing of treatment initiation and cessation, therapy mode, type of anticoagulation, and management of fluid overload. While Level 1 evidence exists for RRT dosing in AKI, all the studies contributing to this evidence base employed fixed-dose regimens throughout a patient's continuous RRT (CRRT) course, without regard for the possibility of individualizing treatment dose according to the clinical status of a given patient at a specific time. As opposed to CRRT dose, no consensus about the timing of RRT in critically ill AKI patients exists currently. While numerous clinical trials over the past 40 years have attempted to assess "early" versus "late" initiation of RRT, they have been plagued by a myriad of methodological problems, including their largely observational nature and the widely varying definitions of early and late initiation. Although questions about the appropriate timing of CRRT discontinuation arise very frequently in clinical practice, even less information is available in the literature to guide this important decision. The aim of this review is to provide a comprehensive update on RRT delivery to critically ill AKI patients, with specific attention paid to treatment dose and timing and emphasis on addressing the practical questions that arise in daily clinical practice., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: Renal replacement therapy may be required for acute kidney injury treatment in neonates with complex cardiac conditions. Continuous veno-venous hemofiltration is applied safely in this population but no published recommendations for dose prescription in neonates currently exist. The aim of our study was to evaluate the effects of a relatively small dialysis dose on critically ill neonates., Design: Retrospective analysis of clinical charts., Setting: Pediatric Cardiac ICU., Patients: Ten critically ill neonates with severe acute kidney injury were analyzed. The primary indication for continuous veno-venous hemofiltration initiation was severe fluid overload with oligoanuria., Interventions: None., Measurements and Main Results: The median (range) age and weight were 3 days (1-12 d) and 2.6 kg (2.1-4.2 kg), respectively, whereas the median continuous veno-venous hemofiltration duration was 17 days (3-63 d). Median prescribed blood flow rate, replacement fluid rate, and net ultrafiltration rate were 12 mL/min (9-50 mL/min), 100 mL/hr (40-200 mL/hr), and 20 mL/hr (5-45 mL/hr), respectively. The median effluent-based continuous veno-venous hemofiltration dose was 35 mL/kg/hr (11-66 mL/kg/hr), whereas the median delivered daily Kt/V per session (24 hr) was 0.5 (0.01-1.8). However, for treatment sessions lasting less than or equal to 12 versus greater than or equal to 12 hours per session, the median prescribed effluent dose was 41 (11-66) and 32 (17-60) mL/kg/hr, respectively (p = 0.06), whereas the delivered creatinine daily Kt/V values were 0.3 (0.01-0.9) and 0.9 (0.5-1.8), respectively (p < 0.0001). An inverse correlation was found between delivered daily Kt/V and the blood concentration differences of both creatinine (r = -0.3; p = 0.0093) and urea (r = -0.3; p = 0.0028) measured at the end and the beginning of a 24-hour treatment. The decrease of creatinine concentration was significantly greater during 24-hour treatment sessions with a delivered daily Kt/V greater than 0.9 than during those with daily Kt/V less than 0.9., Conclusions: Based on these findings, we propose on a provisional basis the use of daily Kt/V as a measure of continuous renal replacement therapy adequacy for critically ill neonates.

Purpose of Review: The current review analyzes the current pharmacologic approaches in cardiac surgery-associated acute kidney injury and renal replacement/support therapies., Recent Findings: Hemodynamic management and promising therapies, including atrial natriuretic peptide, calcium sensitizer inodilators, and mesenchymal stem cells have been discussed. Encouraging results from pre-emptive renal replacement therapies have been also addressed., Summary: Cardiac surgery is responsible for the highest risk of renal dysfunction with respect to other surgical settings. A number of different and coacting insults, including toxins, renal hypoperfusion, ischemia-reperfusion injury, and systemic inflammation, are leading causes of this frequent complication. Intense research is ongoing on the treatment of established cardiac surgery-associated acute kidney injury and, in this view, a holistic approach including preoperative data, risk stratification, prevention, timely diagnosis, and aggressive intervention can limit the burdening consequences of renal dysfunction in these patients. Although no specific pharmacologic and nonpharmacologic strategy can be currently recommended outside clinical research, the prompt identification of renal dysfunction and the application of multimodal treatments are fundamental aspects. Right ventricular dysfunction and increased central venous pressure, frequently affecting cardiac surgery patients, potentially lead to congestive renal dysfunction. Hemodynamic management covers a central role in these cases.

Background/aims: Delivered dialysis therapy is routinely measured in the management of patients with end-stage renal disease; yet, the quantification of renal replacement prescription and delivery in acute kidney injury (AKI) is less established. While continuous renal replacement therapy (CRRT) is widely understood to have greater solute clearance capabilities relative to intermittent therapies, neither urea nor any other solute is specifically employed for CRRT dose assessments in clinical practice at present. Instead, the normalized effluent rate is the gold standard for CRRT dosing, although this parameter does not provide an accurate estimation of actual solute clearance for different modalities., Methods: Because this situation has created confusion among clinicians, we reappraise dose prescription and delivery for CRRT., Results: A critical review of RRT quantification in AKI is provided., Conclusion: We propose an adaptation of a maintenance dialysis parameter (standard Kt/V) as a benchmark to supplement effluent-based dosing of CRRT. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=475457., (© 2017 S. Karger AG, Basel.)

This article reports the conclusions of a consensus expert conference on the basic principles and nomenclature of renal replacement therapy (RRT) currently utilized to manage acute kidney injury (AKI). This multidisciplinary consensus conference discusses common definitions, components, techniques, and operations of the machines and platforms used to deliver extracorporeal therapies, utilizing a "machine-centric" rather than a "patient-centric" approach. We provide a detailed description of the performance characteristics of membranes, filters, transmembrane transport of solutes and fluid, flows, and methods of measurement of delivered treatment, focusing on continuous renal replacement therapies (CRRT) which are utilized in the management of critically ill patients with AKI. This is a consensus report on nomenclature harmonization for principles of extracorporeal renal replacement therapies. Devices and operations are classified and defined in detail to serve as guidelines for future use of terminology in papers and research.

Purpose: Acute kidney injury (AKI) is a frequent complication in high-risk patients undergoing major surgery and is associated with longer hospital stay, increased risk for nosocomial infection and significantly higher costs., Materials and Methods: A prospective observational study exploring the incidence of AKI (AKIN classification at any stage) in high-risk patients within 48 hours after major abdominal surgery was conducted. Patients' preoperative characteristics, intraoperative management, and outcome were evaluated for associations with AKI using a logistic regression model., Results: Data from 258 patients were analyzed. Thirty-one patients (12%) developed AKI, reaching the AKIN stage 1. No patient reached an AKIN stage higher than 1. AKI patients were older (75.2 vs 70.2 years; P = 0.0113) and had a higher body mass index (26.5 vs 25.1 kg/m(2)). In addition, AKI patients had a significantly longer ICU length of stay (3.4 vs 2.4 days; P= .0017). Creatinine levels of AKI patients increased significantly compared to the preoperative levels at 24 (P= .0486), 48 (P= .0011) and 72 hours (P= .0055), while after 72 hours it showed a downwards trend. At ICU discharge, 28 out of 31 patients (90.3%) recovered preoperative levels. Multivariate analysis identified age (OR 1.088; P= .002) and BMI (OR 1.124; P= .022) as risk factors for AKI development. Moreover, AKI development was an independent risk factor for ICU stays longer than 48 hours (OR 2.561; P= .019)., Conclusions: Mild AKI is a not rare complication in high-risk patients undergoing major abdominal surgery. Although in almost the totality of cases, the indicators of renal function recovered to preoperative levels, post-operative AKI represents a primary risk factor for a prolonged ICU stay., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The kidneys play a crucial role in the regulation of electrolytes and acid-base homeostasis. Urinary Strong Ion Difference (SIDu = NaU + KU-ClU) represents an important aspect of renal acid-base regulation. We evaluated the role of SIDu as a marker of renal dysfunction in critically ill patients., Materials and Methods: Patients admitted to the Medical Intensive Care Unit with a diagnosis of AKI for whom concomitant urinary samples available for SIDu calculation were retrospectively reviewed and staged according to KDIGO criteria for 3 days from inclusion. Patients were classified as Recovered (R-AKI) or Persistent-AKI (P-AKI) whether they exited KDIGO criteria within the 3-day observation period or not. A control group with normal renal function and normal serum acid-base and electrolytes was prospectively recruited in order to identify reference SIDu values., Results: One-hundred-and-forty-three patients with a diagnosis of AKI were included: 77 with R-AKI, and 66 with P-AKI. Thirty-six controls were recruited. Patients with P-AKI had more severe renal dysfunction and higher mortality than patients with R-AKI (SCr 2.23(IQR:1.68-3.45) and 1.81(IQR1.5-2.5) mg/dl respectively, p<0.001; 24-h UO 1297(950) and 2100(1094) ml respectively, p = 0.003); 30-d mortality, 39% and 13% respectively; p<0.001). SIDu significantly differed between groups, with rising values from controls to P-AKI groups (16.4(12), 30(24) and 47.3(21.5) mEq/l respectively, p<0.001)., Discussion: SIDu may be a simple and inexpensive tool in AKI patients' evaluation. Further research is needed to evaluate the ability of SIDu to identify patients with renal dysfunction before derangements in serum creatinine or urine output are observed.

Acute renal replacement therapy (ARRT) is today routinely applied in critically ill patients with acute kidney injury. Nevertheless, differently from other therapies in the acute care setting which have specific posology, duration of treatment, serum through and peak levels and clearly predetermined continuous or intermittent way of administration, ARRT may appear difficult to dose, prescribe, deliver and monitor. Additionally, current literature has provided controversial results about many aspects of ARRT administration. This review will focus on the definition of dialytic dose, extensively detailing different dimensions of ARRT delivery: as a matter of fact, the provision of a dialytic session to a critically ill patient should not be limited to the simplistic mathematical calculation of an exact dose. Adequacy of ARRT implies the concomitant consideration of more complex issues such as timing, modality and techniques of ARRT delivery, anticoagulation and substitution fluids choice, membrane selection, monitor accuracy, the role of fluid overload and other patients' comorbidities. The capacity of clinicians of considering all these aspects, adapting the different dimensions of dose to the actual patients' needs, might be the fundamental missing element in the pathway towards significant outcome improvements of critically ill AKI patients needing ARRT.

Background: Continuous renal replacement therapy (CRRT) and peritoneal dialysis are the preferred forms of dialysis delivery in critically ill children for the treatment of severe acute kidney injury. The epidemiology and the outcome of acute pediatric dialysis will be reviewed., Summary: The prospective pediatric CRRT (pCRRT) registry has provided important epidemiologic information: pCRRT is required in about 5% of patients in pediatric intensive care units, and the mortality rate of these patients is about 60%. CRRT outcomes are significantly associated with age, the presence of multiple organ dysfunction syndrome and the amount of fluid overload in children before CRRT inception. The timing and the dose of pCRRT are to be further evaluated in prospective trials. A final aspect worthy of review is a technical issue: the accuracy of new-generation CRRT monitors and novel dedicated circuits that have been developed. In future years, the delivery and the outcome of pCRRT are expected to significantly improve, with the target of expanding and anticipating dialysis initiation in critically ill pediatric patients., (© 2016 S. Karger AG, Basel.)

In modern intensive care medicine, lungs and kidneys frequently are involved in the context of multiorgan failure. When organ dysfunction occurs, the primary clinical management of critically ill patients is based on support/replacement of organ function until recovery. Mechanical ventilation is the first-line intervention in case of respiratory failure, but in most severe cases may, itself, cause ventilator-induced lung injury. The same inflammatory mechanism also may harm the kidney through mediator spillover from the injured lungs into the bloodstream. To limit the deleterious effects of mechanical ventilation and avoid excessive carbon dioxide accumulation, devices for extracorporeal CO2 removal (ECCO2R), have been developed. Some consistent clinical experience currently has been reached in patients with obstructive pulmonary disease and acute respiratory distress syndrome. Interestingly, ECCO2R recently has been coupled with continuous renal replacement therapy systems into specific lung-renal support. The results from the first experimental and clinical applications are encouraging: it is expected that a system including continuous renal replacement therapy and ECCO2R will develop from the current pioneering attempts into a feasible multiple-organ support platform to become commonly used as a routine tool in intensive care units. This review focuses on recent literature and clinical applications of renal-pulmonary support with specific attention to technical aspects of the most recent materials and devices., (Copyright © 2016 Elsevier Inc. All rights reserved.)