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Background: Sepsis is a leading cause of acute kidney injury requiring continuous kidney replacement therapy (CKRT) and CKRT can alter drug pharmacokinetics (PK). Cefepime is used commonly in critically ill children and is cleared by CKRT, yet data regarding cefepime PK and pharmacodynamic (PD) target attainment in children receiving CKRT are scarce, so we performed Monte Carlo simulations (MCS) of cefepime dosing strategies in children receiving CKRT. Methods: We developed a CKRT "module" in the precision dosing software Edsim++. The module was added into a pediatric cefepime PK model. 1000-fold MCS were performed using six dosing strategies in patients aged 2–25 years and ≥ 10 kg with differing residual kidney function (estimated glomerular filtration rate of 5 vs 30 mL/min/1.73 m2), CKRT prescriptions, (standard-dose total effluent flow of 2500 mL/h/1.73 m2 vs high-dose of 8000 mL/h/1.73 m2), and fluid accumulation (0–30%). Probability of target attainment (PTA) was defined by percentage of patients with free concentrations exceeding bacterial minimum inhibitory concentration (MIC) for 100% of the dosing interval (100% fT > 1xMIC) and 4xMIC using an MIC of 8 mg/L for Pseudomonas aeruginosa. Results: Assuming standard-dose dialysis and minimal kidney function, > 90% PTA was achieved for 100% fT > 1x MIC with continuous infusions (CI) of 100–150 mg/kg/day (max 4/6 g) and 4-h infusions of 50 mg/kg (max 2 g), but > 90% PTA for 100% fT > 4x MIC was only achieved by 150 mg/kg CI. Decreased PTA was seen with less frequent dosing, shorter infusions, higher-dose CKRT, and higher residual kidney function. Conclusions: Our new CKRT-module was successfully added to an existing cefepime PK model for MCS in young patients on CKRT. When targeting 100% fT > 4xMIC or using higher-dose CKRT, CI would allow for higher PTA than intermittent dosing. [ABSTRACT FROM AUTHOR]

Abstract Background Sepsis is a leading cause of acute kidney injury requiring continuous kidney replacement therapy (CKRT) and CKRT can alter drug pharmacokinetics (PK). Cefepime is used commonly in critically ill children and is cleared by CKRT, yet data regarding cefepime PK and pharmacodynamic (PD) target attainment in children receiving CKRT are scarce, so we performed Monte Carlo simulations (MCS) of cefepime dosing strategies in children receiving CKRT. Methods We developed a CKRT “module” in the precision dosing software Edsim++. The module was added into a pediatric cefepime PK model. 1000-fold MCS were performed using six dosing strategies in patients aged 2–25 years and ≥ 10 kg with differing residual kidney function (estimated glomerular filtration rate of 5 vs 30 mL/min/1.73 m2), CKRT prescriptions, (standard-dose total effluent flow of 2500 mL/h/1.73 m2 vs high-dose of 8000 mL/h/1.73 m2), and fluid accumulation (0–30%). Probability of target attainment (PTA) was defined by percentage of patients with free concentrations exceeding bacterial minimum inhibitory concentration (MIC) for 100% of the dosing interval (100% fT > 1xMIC) and 4xMIC using an MIC of 8 mg/L for Pseudomonas aeruginosa. Results Assuming standard-dose dialysis and minimal kidney function, > 90% PTA was achieved for 100% fT > 1x MIC with continuous infusions (CI) of 100–150 mg/kg/day (max 4/6 g) and 4-h infusions of 50 mg/kg (max 2 g), but > 90% PTA for 100% fT > 4x MIC was only achieved by 150 mg/kg CI. Decreased PTA was seen with less frequent dosing, shorter infusions, higher-dose CKRT, and higher residual kidney function. Conclusions Our new CKRT-module was successfully added to an existing cefepime PK model for MCS in young patients on CKRT. When targeting 100% fT > 4xMIC or using higher-dose CKRT, CI would allow for higher PTA than intermittent dosing.

Background: Continuous renal replacement therapy (CKRT) is delivered to some of the most critically ill patients in hospitals. This therapy is expensive and requires coordination of multidisciplinary teams to ensure the prescribed dose is delivered. With increased demands on the critical care nursing staff and increased complexities of patients admitted to critical care units, we evaluated the role of specialized renal technologists in ensuring the prescribed dose is delivered. Therefore, the aim of this study is to investigate the impact of supporting intensive care unit nurses with specialized renal technologists on optimizing efficiency of CKRT sessions in the United Arab Emirates. Methods: This is a retrospective study that compared critically ill patients on CKRT overseen by specialized renal technologists versus who are non‐covered in the year 2021. Results: A total of 331 sessions on 158 patients were included in the study. The mean filter life was longer in specialized renal technologists—covered patients compared to the non‐covered group (66 vs. 59 h, p = 0.019). After adjustment by multiple regression analysis for risk factors (i.e., age, gender, mechanical ventilation, sepsis, mean arterial pressure, vasopressors, and SOFA) that may affect CKRT machines' filter life, presence of a specialized renal technologists resulted in significantly longer filter life (co‐efficient 0.129; CI 95% 1.080, 11.970; p‐value: 0.019). Conclusion: Our study suggests that specialized renal technologists play a vital role in prolonging CKRT machine's filter life span and optimizing CKRT machine's efficiency. Further research should focus on other potential benefits of having specialized renal technologists performing CKRT sessions, and to confirm the finding of this study. Additionally, a cost–benefit analysis could be conducted to determine the economic impact of having specialized teams performing CKRT. [ABSTRACT FROM AUTHOR]

Background: Infants with kidney failure (KF) demonstrate poor growth partly due to obligate fluid and protein restrictions. Delivery of liberalized nutrition on continuous kidney replacement therapy (CKRT) is impacted by clinical instability, technical dialysis challenges, solute clearance, and nitrogen balance. We analyzed delivered nutrition and growth in infants receiving CKRT with the Cardio-Renal, Pediatric Dialysis Emergency Machine (Carpediem™). Methods: Single-center observational study of infants receiving CKRT with the Carpediem™ between June 1 and December 31, 2021. We collected prospective circuit characteristics, delivered nutrition, anthropometric measurements, and illness severity Score for Neonatal Acute Physiology-II. As a surrogate to normalized protein catabolic rate in maintenance hemodialysis, we calculated normalized protein nitrogen appearance (nPNA) using the Randerson II continuous dialysis model. Descriptive statistics, Spearman correlation coefficient, Mann Whitney, Wilcoxon signed rank, receiver operating characteristic curves, and Kruskal–Wallis analysis were performed using SAS version 9.4. Results: Eight infants received 31.9 (22.0, 49.7) days of CKRT using mostly (90%) regional citrate anticoagulation. Delivered nutritional volume, protein, total calories, enteral calories, nPNA, and nitrogen balance increased on CKRT. Using parenteral nutrition, 90 ml/kg/day should meet caloric and protein needs. Following initial weight loss of likely fluid overload, exploratory sensitivity analysis suggests weight gain occurred after 14 days of CKRT. Despite adequate nutritional delivery, goal weight (z-score = 0) and growth velocity were not achieved until 6 months after CKRT start. Most (5 infants, 62.5%) survived and transitioned to peritoneal dialysis (PD). Conclusions: Carpediem™ is a safe and efficacious bridge to PD in neonatal KF. Growth velocity of infants on CKRT appears delayed despite delivery of adequate calories and protein. [ABSTRACT FROM AUTHOR]

The accurate interpretation of CRRT machine alarms is crucial in the intensive care setting. ChatGPT, with its advanced natural language processing capabilities, has emerged as a tool that is evolving and advancing in its ability to assist with healthcare information. This study is designed to evaluate the accuracy of the ChatGPT-3.5 and ChatGPT-4 models in addressing queries related to CRRT alarm troubleshooting. This study consisted of two rounds of ChatGPT-3.5 and ChatGPT-4 responses to address 50 CRRT machine alarm questions that were carefully selected by two nephrologists in intensive care. Accuracy was determined by comparing the model responses to predetermined answer keys provided by critical care nephrologists, and consistency was determined by comparing outcomes across the two rounds. The accuracy rate of ChatGPT-3.5 was 86% and 84%, while the accuracy rate of ChatGPT-4 was 90% and 94% in the first and second rounds, respectively. The agreement between the first and second rounds of ChatGPT-3.5 was 84% with a Kappa statistic of 0.78, while the agreement of ChatGPT-4 was 92% with a Kappa statistic of 0.88. Although ChatGPT-4 tended to provide more accurate and consistent responses than ChatGPT-3.5, there was no statistically significant difference between the accuracy and agreement rate between ChatGPT-3.5 and -4. ChatGPT-4 had higher accuracy and consistency but did not achieve statistical significance. While these findings are encouraging, there is still potential for further development to achieve even greater reliability. This advancement is essential for ensuring the highest-quality patient care and safety standards in managing CRRT machine-related issues. [ABSTRACT FROM AUTHOR]

Background: In a group of children admitted to the paediatric intensive care unit (PICU) receiving continuous kidney replacement therapy (CKRT), we aim to evaluate the data about their hemodynamic, ventilation and analgo-sedation profile in the first 24 h of treatment and possible associations with mortality. Methods: Retrospective cohort study of children admitted to the PICU of the University Hospital of Padova undergoing CKRT between January 2011 and March 2021. Data was collected at baseline (T0), after 1 h (T1) and 24 h (T24) of CKRT treatment. The differences in outcome measures were compared between these time points, and between survivors and non-survivors. Results: Sixty-nine patients received CKRT, of whom 38 (55%) died during the PICU stay. Overall, the vasoactive inotropic score and the adrenaline dose increased at T1 compared to T0 (p = 0.012 and p = 0.022, respectively). Compared to T0, at T24 patients showed an improvement in the following ventilatory parameters: Oxygenation Index (p = 0.005), Oxygenation Saturation Index (p = 0.013) PaO2/FiO2 ratio (p = 0.005), SpO2/FiO2 ratio (p = 0.002) and Mean Airway Pressure (p = 0.016). These improvements remained significant in survivors (p = 0.01, p = 0.027, p = 0.01 and p = 0.015, respectively) but not in non-survivors. No changes in analgo-sedative drugs have been described. Conclusions: CKRT showed a significant impact on hemodynamics and ventilation in the first 24 h of treatment. We observed a significant rise in the inotropic/vasoactive support required after 1 h of treatment in the overall population, and an improvement in the ventilation parameters at 24 h only in survivors. [ABSTRACT FROM AUTHOR]

Advancements in pediatric dialysis generally rely on adaptation of technology originally developed for adults. However, in the last decade, particular attention has been paid to neonatal extracorporeal therapies for acute kidney care, an area in which technology has made giant strides in recent years. Peritoneal dialysis (PD) is the kidney replacement therapy (KRT) of choice in the youngest age group because of its simplicity and effectiveness. However, extracorporeal blood purification provides more rapid clearance of solutes and faster fluid removal. Hemodialysis (HD) and continuous KRT (CKRT) are thus the most used dialysis modalities for pediatric acute kidney injury (AKI) in developed countries. The utilization of extracorporeal dialysis for small children is associated with a series of clinical and technical challenges which have discouraged the use of CKRT in this population. The revolution in the management of AKI in newborns has started recently with the development of new CKRT machines for small infants. These new devices have a small extracorporeal volume that potentially prevents the use of blood to prime lines and dialyzer, allow a better volume control and the use of small-sized catheter without compromising the blood flow amount. Thanks to the development of new dedicated devices, we are currently dealing with a true "scientific revolution" in the management of neonates and infants who require an acute kidney support. [ABSTRACT FROM AUTHOR]

Abstract Background On December 29, 2021, during the delta wave of the Coronavirus Disease 2019 (COVID-19) pandemic, the stock of premanufactured solutions used for continuous kidney replacement therapy (CKRT) at the University of New Mexico Hospital (UNMH) was nearly exhausted with no resupply anticipated due to supply chain disruptions. Within hours, a backup plan, devised and tested 18 months prior, to locally produce CKRT dialysate was implemented. This report describes the emergency implementation and outcomes of this on-site CKRT dialysate production system. Methods This is a single-center retrospective case series and narrative report describing and reporting the outcomes of the implementation of an on-site CKRT dialysate production system. All adults treated with locally produced CKRT dialysate in December 2021 and January 2022 at UNMH were included. CKRT dialysate was produced locally using intermittent hemodialysis machines, hemodialysis concentrate, sterile parenteral nutrition bags, and connectors made of 3-D printed biocompatible rigid material. Outcomes analyzed included dialysate testing for composition and microbiologic contamination, CKRT prescription components, patient mortality, sequential organ failure assessment (SOFA) scores, and catheter-associated bloodstream infections (CLABSIs). Results Over 13 days, 22 patients were treated with 3,645 L of locally produced dialysate with a mean dose of 20.0 mL/kg/h. Fluid sample testing at 48 h revealed appropriate electrolyte composition and endotoxin levels and bacterial colony counts at or below the lower limit of detection. No CLABSIs occurred within 7 days of exposure to locally produced dialysate. In-hospital mortality was 81.8% and 28-day mortality was 68.2%, though illness severity was high, with a mean SOFA score of 14.5. Conclusions Though producing CKRT fluid with IHD machines is not novel, this report represents the first description of the rapid and successful implementation of a backup plan for local CKRT dialysate production at a large academic medical center in the U.S. during the COVID-19 pandemic. Though conclusions are limited by the retrospective design and limited sample size of our analysis, our experience could serve as a guide for other centers navigating similar severe supply constraints in the future.

Introduction: Tumor lysis syndrome (TLS) is often diagnosed in children with hematological malignancies and can be life threatening due to metabolic disturbances. Continuous renal replacement therapy (CKRT) can reverse these disturbances relatively quickly when conventional medical management fails. Our objective was to investigate the benefit of CKRT in the management of TLS in children admitted to the intensive care unit with hematologic malignancies. In addition, we sought to assess risk factors for acute kidney injury (AKI) in the setting of TLS. Methods: Retrospective review of all children admitted to the intensive care unit with TLS who received CKRT from January 2012 to August 2022. Results: Among 222 children hospitalized with TLS from January 2012 to August 2022, 20 (9%) underwent CKRT to manage TLS in the intensive care unit. The patients' median age was 13 years (range 3-17 y), and most were males (18/20). Tcell acute lymphoblastic leukemia was the most common diagnosis (n=10), followed by acute myeloid leukemia (n=4), Burkitt lymphoma (n=4), and B-cell acute lymphoblastic leukemia (n=2). Five patients required mechanical ventilation, and 2 required vasopressors. The most common indication for CKRT was hyperphosphatemia, followed by, hyperuricemia, and hyperkalemia. All metabolic abnormalities corrected within 12 h of initiation of CKRT. CKRT courses were brief, with a median duration of 2 days (range 1-7 days). Having higher serum phosphorus levels 12 h preceding CKRT was significantly associated with severe acute kidney injury (AKI). The median phosphorus level was 6.4 mg/dL in children with no/mild AKI and 10.5 mg/dL in children with severe AKI (p=0.0375). Serum uric acid levels before CKRT were not associated with AKI. All children survived to hospital discharge, and the one-year survival rate was 90%. Conclusion: CKRT is safe in children with hematologic malignancies with severe TLS and reverses metabolic derangements within 6-12 h. Most patients had AKI at the initiation of CKRT but did not require long-term kidney replacement therapy. Hyperphosphatemia before initiation of CKRT is associated with higher risk of AKI. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal therapies (ET) are increasingly used in pediatric settings as adjuvant therapeutic strategies for overwhelming inflammatory conditions. Although these treatments seem to be effective for removing inflammatory mediators, their influence on antimicrobials pharmacokinetic should not be neglected. Methods: A prospective observational study of children admitted to the pediatric intensive care unit (PICU) with a diagnosis of sepsis/septic shock. All critically ill children received hemoadsorption treatment with CytoSorb (CS) in combination with CKRT. Therapeutic drug monitoring has been performed on 10 critically ill children, testing four antimicrobial molecules: meropenem, ceftazidime, amikacin and levofloxacin. In order to evaluate the total and isolated CKRT and CS contributions to antibiotic removal, blood samples at each circuit point (post-hemofilter, post-CS and in the effluent line) were performed. Therefore, the clearance and mass Removal (MR) of the hemofilter and CS were calculated. Results: Our preliminary report describes a different impact of CS on these target drugs removal: CS clearance was low for amikacine (6–12%), moderate for ceftazidime (43%) and moderate to high for levofloxacine (52–72%). Higher MR and clearance were observed with CKRT compared to CS. To the best of our knowledge, this is the first report regarding pharmacokinetic dynamics in critically ill children treated with CKRT and CS for septic shock. [ABSTRACT FROM AUTHOR]

Background: On December 29, 2021, during the delta wave of the Coronavirus Disease 2019 (COVID-19) pandemic, the stock of premanufactured solutions used for continuous kidney replacement therapy (CKRT) at the University of New Mexico Hospital (UNMH) was nearly exhausted with no resupply anticipated due to supply chain disruptions. Within hours, a backup plan, devised and tested 18 months prior, to locally produce CKRT dialysate was implemented. This report describes the emergency implementation and outcomes of this on-site CKRT dialysate production system. Methods: This is a single-center retrospective case series and narrative report describing and reporting the outcomes of the implementation of an on-site CKRT dialysate production system. All adults treated with locally produced CKRT dialysate in December 2021 and January 2022 at UNMH were included. CKRT dialysate was produced locally using intermittent hemodialysis machines, hemodialysis concentrate, sterile parenteral nutrition bags, and connectors made of 3-D printed biocompatible rigid material. Outcomes analyzed included dialysate testing for composition and microbiologic contamination, CKRT prescription components, patient mortality, sequential organ failure assessment (SOFA) scores, and catheter-associated bloodstream infections (CLABSIs). Results: Over 13 days, 22 patients were treated with 3,645 L of locally produced dialysate with a mean dose of 20.0 mL/kg/h. Fluid sample testing at 48 h revealed appropriate electrolyte composition and endotoxin levels and bacterial colony counts at or below the lower limit of detection. No CLABSIs occurred within 7 days of exposure to locally produced dialysate. In-hospital mortality was 81.8% and 28-day mortality was 68.2%, though illness severity was high, with a mean SOFA score of 14.5. Conclusions: Though producing CKRT fluid with IHD machines is not novel, this report represents the first description of the rapid and successful implementation of a backup plan for local CKRT dialysate production at a large academic medical center in the U.S. during the COVID-19 pandemic. Though conclusions are limited by the retrospective design and limited sample size of our analysis, our experience could serve as a guide for other centers navigating similar severe supply constraints in the future. [ABSTRACT FROM AUTHOR]

Regional Citrate Anticoagulation (RCA) is considered the first-line anticoagulation for Continuous Kidney Replacement Therapy (CKRT). The RCA requires strict protocols and trained staff to avoid unsafe use and ensure its benefit. We have analyzed all our CKRT prescriptions from December 2020 to April 2022 anonymously, collecting data on CKRT, lab tests, clinical conditions, and complications of RCA. In addition, in order to better detect citrate accumulation, we have performed an RCA protocol by reducing the CaTot/Ca2+ ratio cut-off from 2.50 to 2.40 and increasing the number of calcium checks according to its trend. Among the 374 patients in CKRT, 104 received RCA prescriptions, of which 11 (10.6%) were discontinued: 4 for the suspicion of citrate accumulation, 1 for the development of metabolic alkalosis, 1 for the shift to a different CKRT procedure due to the need for a higher bicarbonate dose, 4 for the elevation of hepatocytolysis indexes, and 1 due to a preemptive discontinuation following massive post-surgery bleeding. None of the patients have had citrate toxicity as indicated by a CaTot/Ca2+ greater than 2.50, and our protocol has allowed the early identification of patients who might develop clinical citrate toxicity. [ABSTRACT FROM AUTHOR]

Kidney support therapy (KST), previously referred to as Renal Replacement Therapy, is utilized to treat children and adults with severe acute kidney injury (AKI), fluid overload, inborn errors of metabolism, and kidney failure. Several forms of KST are available including peritoneal dialysis (PD), intermittent hemodialysis (iHD), and continuous kidney support therapy (CKST). Traditionally, extracorporeal KST (CKST and iHD) in neonates has had unique challenges related to small patient size, lack of neonatal-specific devices, and risk of hemodynamic instability due to large extracorporeal circuit volume relative to patient total blood volume. Thus, PD has been the most commonly used modality in infants, followed by CKST and iHD. In recent years, CKST machines designed for small children and novel filters with smaller extracorporeal circuit volumes have emerged and are being used in many centers to provide neonatal KST for toxin removal and to achieve fluid and electrolyte homeostasis, increasing the options available for this unique and vulnerable group. These new treatment options create a dramatic paradigm shift with recalibration of the benefit: risk equation. Renewed focus on the infrastructure required to deliver neonatal KST safely and effectively is essential, especially in programs/units that do not traditionally provide KST to neonates. Building and implementing a neonatal KST program requires an expert multidisciplinary team with strong institutional support. In this review, we first describe the available neonatal KST modalities including newer neonatal and infant-specific platforms. Then, we describe the steps needed to develop and sustain a neonatal KST team, including recommendations for provider and nursing staff training. Finally, we describe how quality improvement initiatives can be integrated into programs. [ABSTRACT FROM AUTHOR]

Abstract Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid–base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong (“we recommend”) or weak/conditional (“we suggest”), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8–12 mmol/L or anion gap 23–27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is

IntroductionTumor lysis syndrome (TLS) is often diagnosed in children with hematological malignancies and can be life threatening due to metabolic disturbances. Continuous renal replacement therapy (CKRT) can reverse these disturbances relatively quickly when conventional medical management fails. Our objective was to investigate the benefit of CKRT in the management of TLS in children admitted to the intensive care unit with hematologic malignancies. In addition, we sought to assess risk factors for acute kidney injury (AKI) in the setting of TLS.MethodsRetrospective review of all children admitted to the intensive care unit with TLS who received CKRT from January 2012 to August 2022.ResultsAmong 222 children hospitalized with TLS from January 2012 to August 2022, 20 (9%) underwent CKRT to manage TLS in the intensive care unit. The patients’ median age was 13 years (range 3-17 y), and most were males (18/20). T-cell acute lymphoblastic leukemia was the most common diagnosis (n=10), followed by acute myeloid leukemia (n=4), Burkitt lymphoma (n=4), and B-cell acute lymphoblastic leukemia (n=2). Five patients required mechanical ventilation, and 2 required vasopressors. The most common indication for CKRT was hyperphosphatemia, followed by, hyperuricemia, and hyperkalemia. All metabolic abnormalities corrected within 12 h of initiation of CKRT. CKRT courses were brief, with a median duration of 2 days (range 1-7 days). Having higher serum phosphorus levels 12 h preceding CKRT was significantly associated with severe acute kidney injury (AKI). The median phosphorus level was 6.4 mg/dL in children with no/mild AKI and 10.5 mg/dL in children with severe AKI (p=0.0375). Serum uric acid levels before CKRT were not associated with AKI. All children survived to hospital discharge, and the one-year survival rate was 90%.ConclusionCKRT is safe in children with hematologic malignancies with severe TLS and reverses metabolic derangements within 6-12 h. Most patients had AKI at the initiation of CKRT but did not require long-term kidney replacement therapy. Hyperphosphatemia before initiation of CKRT is associated with higher risk of AKI.

Rationale & Objective: Continuous kidney replacement therapy (CKRT) is the predominant form of acute kidney replacement therapy used for critically ill adult patients with acute kidney injury (AKI). Given the variability in CKRT practice, a contemporary understanding of its epidemiology is necessary to improve care delivery. Study Design: Multicenter, prospective living registry. Setting & Population: 1,106 critically ill adults with AKI requiring CKRT from December 2013 to January 2021 across 5 academic centers and 6 intensive care units. Patients with pre-existing kidney failure and those with coronavirus 2 infection were excluded. Exposure: CKRT for more than 24 hours. Outcomes: Hospital mortality, kidney recovery, and health care resource utilization. Analytical Approach: Data were collected according to preselected timepoints at intensive care unit admission and CKRT initiation and analyzed descriptively. Results: Patients’ characteristics, contributors to AKI, and CKRT indications differed among centers. Mean (standard deviation) age was 59.3 (13.9) years, 39.7% of patients were women, and median [IQR] APACHE-II (acute physiologic assessment and chronic health evaluation) score was 30 [25-34]. Overall, 41.1% of patients survived to hospital discharge. Patients that died were older (mean age 61 vs. 56.8, P

Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid–base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong ("we recommend") or weak/conditional ("we suggest"), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8–12 mmol/L or anion gap 23–27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR. [ABSTRACT FROM AUTHOR]

Background: Continuous kidney replacement therapy (CKRT) is a mainstay of therapy for management of severe acute kidney injury (AKI) in critically ill pediatric patients. There is limited data on the risk of chronic kidney disease (CKD) after discharge in this population. Methods: This is a single-center, retrospective cohort study of all pediatric patients ages 0–17 years who received CKRT from 2013 to 2017. The study excluded patients with pre-existing CKD, those who died prior to discharge, and those who had insufficient follow-up data. Patients were followed after hospital discharge and electronic health record data was collected and analyzed to assess for incidence of and risk factors for kidney sequelae. Results: A total of 42 patients were followed at a median time of 27 months (IQR 17.2, 39.8). Of these, 26.2% had evidence of CKD and 19% were at risk for CKD. Lower eGFR at hospital discharge was associated with increased odds of kidney sequelae (aOR 0.985; 95% CI 0.972, 0.996). Ages 0– < 1 and 12–17 were not significantly different (aOR 0.235, 95% CI 0.024, 1.718) and had the highest incidence of kidney sequelae (50% and 77%, respectively). Ages 1–5 and 6–11 had a decreased odds of kidney sequelae compared to the 12–17 year age group (aOR 0.098; 95% CI 0.009, 0.703 and aOR 0.035; 95% CI 0.001, 0.39, respectively). Only 54.8% of patients (n = 23) were seen in the nephrology clinic after discharge. Conclusions: Patients who receive CKRT for AKI have a significant risk of CKD, while follow-up with a pediatric nephrologist in these high-risk patients is sub-optimal. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Background: Extracorporeal therapies (ET) are increasingly used in pediatric settings as adjuvant therapeutic strategies for overwhelming inflammatory conditions. Although these treatments seem to be effective for removing inflammatory mediators, their influence on antimicrobials pharmacokinetic should not be neglected. Methods: A prospective observational study of children admitted to the pediatric intensive care unit (PICU) with a diagnosis of sepsis/septic shock. All critically ill children received hemoadsorption treatment with CytoSorb (CS) in combination with CKRT. Therapeutic drug monitoring has been performed on 10 critically ill children, testing four antimicrobial molecules: meropenem, ceftazidime, amikacin and levofloxacin. In order to evaluate the total and isolated CKRT and CS contributions to antibiotic removal, blood samples at each circuit point (post-hemofilter, post-CS and in the effluent line) were performed. Therefore, the clearance and mass Removal (MR) of the hemofilter and CS were calculated. Results: Our preliminary report describes a different impact of CS on these target drugs removal: CS clearance was low for amikacine (6–12%), moderate for ceftazidime (43%) and moderate to high for levofloxacine (52–72%). Higher MR and clearance were observed with CKRT compared to CS. To the best of our knowledge, this is the first report regarding pharmacokinetic dynamics in critically ill children treated with CKRT and CS for septic shock.

Abstract Background Regional citrate anticoagulation (RCA) for the prevention of clotting of the extracorporeal blood circuit during continuous kidney replacement therapy (CKRT) has been employed in limited fashion because of the complexity and complications associated with certain protocols. Hypertonic citrate infusion to achieve circuit anticoagulation results in variable systemic citrate- and sodium load and increases the risk of citrate accumulation and hypernatremia. The practice of “single starting calcium infusion rate for all patients” puts patients at risk for clinically significant hypocalcemia if filter effluent calcium losses exceed replacement. A fixed citrate to blood flow ratio, personalized effluent and pre-calculated calcium infusion dosing based on tables derived through kinetic analysis enable providers to use continuous veno-venous hemo-diafiltration (CVVHDF)-RCA in patients with liver citrate clearance of at least 6 L/h. Methods This was a single-center prospective observational study conducted in intensive care unit patients triaged to be treated with the novel pre-calculated CVVHDF-RCA “Non-shock” protocol. RCA efficacy outcomes were time to first hemofilter loss and circuit ionized calcium (iCa) levels. Safety outcomes were surrogate of citrate accumulation (TCa/iCa ratio) and the incidence of acid-base and electrolyte complications. Results Of 53 patients included in the study, 31 (59%) had acute kidney injury and 12 (22.6%) had the diagnosis of cirrhosis at the start of CVVHDF-RCA. The median first hemofilter life censored for causes other than clotting exceeded 70 h. The cumulative incidence of hypernatremia (Na > 148 mM), metabolic alkalosis (HCO3- > 30 mM), hypocalcemia (iCa 1.5 mM) were 1/47 (1%), 0/50 (0%), 1/53 (2%), 1/53 (2%) respectively and were not clinically significant. The median (25th–75th percentile) of the highest TCa/iCa ratio for every 24-h interval on CKRT was 1.99 (1.91–2.13). Conclusions The fixed citrate to blood flow ratio, as opposed to a titration approach, achieves adequate circuit iCa (

Objective: Continuous kidney replacement therapy (CKRT) is the primary therapeutic modality utilized in hemodynamically unstable patients with severe acute kidney injury. As the circuit is extracorporeal, it poses an increased risk of blood clotting and circuit loss; frequent circuit losses affect the provider's ability to provide optimal treatment. The objective of this meta-analysis is to evaluate the safety and efficacy of the extracorporeal anticoagulants in the pediatric CKRT population. Data Sources: We conducted a literature search on PubMed/Medline and Embase for relevant citations. Study Selection: Studies were included if they involved patients under the age of 18 years undergoing CKRT, with the use of anticoagulation (heparin, citrate, or prostacyclin) as a part of therapy. Only English articles were included in the study. Data Extraction: Initial search yielded 58 articles and a total of 24 articles were included and reviewed. A meta-analysis was performed focusing on the safety and effectiveness of regional citrate anticoagulation (RCA) vs unfractionated heparin (UFH) anticoagulants in children. Data Synthesis: RCA had statistically significantly longer circuit life of 50.65 hours vs. UFH of 42.10 hours. Two major adverse effects metabolic alkalosis and electrolyte imbalance seen more commonly in RCA compared to UFH. There was not a significant difference in the risk of systemic bleeding when comparing RCA vs. UFH. Conclusion: RCA is the preferred anticoagulant over UFH due to its significantly longer circuit life, although vigilant circuit monitoring is required due to the increased risk of electrolyte disturbances. Prostacyclin was not included in the meta-analysis due to the lack of data in pediatric patients. Additional studies are needed to strengthen the study results further. [ABSTRACT FROM AUTHOR]

Background: In critically ill children with acute kidney injury (AKI), continuous kidney replacement therapy (CKRT) enables nutrition provision. The magnitude of amino acid loss during continuous venovenous hemodiafiltration (CVVHDF) is unknown and needs accurate quantification. We investigated the mass removal and clearance of amino acids in pediatric CVVHDF. Methods: This is a prospective observational cohort study of patients receiving CVVHDF from August 2014 to January 2016 in the pediatric intensive care unit (PICU) of a tertiary children's hospital. Results: Fifteen patients (40% male, median age 2.0 (IQR 0.7, 8.0) years) were enrolled. Median PICU and hospital lengths of stay were 20 (9, 59) and 36 (22, 132) days, respectively. Overall survival to discharge was 66.7%. Median daily protein prescription was 2.00 (1.25, 2.80) g/kg/day. Median daily amino acid mass removal was 299.0 (174.9, 452.0) mg/kg body weight, and median daily amino acid mass clearance was 18.2 (13.5, 27.9) ml/min/m2, resulting in a median 14.6 (8.3, 26.7) % protein loss. The rate of amino acid loss increased with increasing dialysis dose and blood flow rate. Conclusion: CVVHDF prescription and related amino acid loss impact nutrition provision, with 14.6% of the prescribed protein removed. Current recommendations for protein provision for children requiring CVVHDF should be adjusted to compensate for circuit-related loss. [ABSTRACT FROM AUTHOR]

Background: Ongoing measures to improve pediatric continuous kidney replacement therapy (CKRT) have lowered mortality rates, shifting the focus to survivor functional status. While septic acute kidney injury generates new morbidity in pediatric critically ill patients, acquired morbidities and functional status of CKRT population are unknown. We predicted that CKRT survivors are at risk for new morbidity and would have worse functional status at PICU discharge compared to baseline, and aimed to describe associated factors. Methods: Retrospective cohort study over 24 months of CKRT patients surviving to PICU discharge in a quaternary children's hospital. Functional outcome was determined by Functional Status Scale (FSS). Results: FSS scores were higher at PICU and hospital discharge compared to baseline. Of 45 CKRT survivors, 31 (69%) had worse FSS score at PICU discharge and 51% had new morbidity (≥3 increase in FSS); majority qualified as moderate to severe disability (FSS ≥10). Four patients (9%) had new tracheostomy, 3 (7%) were ventilator dependent, and 10 (22%) were dialysis dependent. Most (23/45, 51%) required outpatient rehabilitation. Cumulative days on sedation, controlled for illness severity, were independently associated with worse FSS at PICU discharge (aOR 25.18 (3.73, 169.92)). In adjusted analyses, duration of sedation was associated with new morbidity, while neurologic comorbidity, percent fluid overload at CKRT start, and nonrenal comorbidity were associated with moderate to severe disability at PICU discharge when controlled for baseline FSS. Conclusions: CKRT survivors, with new morbidity and worse functional outcomes at PICU discharge, are a newly described vulnerable population requiring targeted follow-up. Deliberate decrease of sedation exposure in patients with decreased clearance due to organ dysfunction needs to be studied as a modifiable risk factor. [ABSTRACT FROM AUTHOR]

Background: Current guidelines for initiation of kidney replacement do not include specific recommendations for prescription parameters and monitoring. Case outline: A 16-year-old girl presented with kidney failure with creatinine of 19.8 mg/dL and BUN of 211 mg/dL. She initiated continuous kidney replacement therapy (CKRT) with clearance of 1,300 mL/min/1.73 m2 which was increased to 1,950 mL/min/1.73 m2 at 17 h of stable therapy. Complications: At 31 h of therapy, she developed generalized seizure activity. CT imaging was negative for acute intracranial process, and EEG demonstrated diffuse encephalopathy. CKRT was discontinued, and BUN was noted to be 47 mg/dL at that time (a 79% reduction from presenting BUN). Key management points: • The potential for development of DDS is not isolated to intermittent hemodialysis and may occur later in presentation. • A decreased clearance rate should be considered in those with risk factors for development of dialysis disequilibrium syndrome (DDS). • Frequent monitoring of BUN/serum osmolality is important to allow for adjustment of the KRT prescription following initiation of therapy. • Additional research is needed to guide risk assessment for DDS and therapeutic timing and goals in the early stages of KRT initiation. • Inclusion of more specific guidelines surrounding DDS would assist in providing important support for nephrologists. List of relevant guidelines: KDIGO clinical practice guideline for acute kidney injury [1] Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease [2] The Renal Association Clinical Practice Guideline Acute Kidney Injury (AKI) [3] The Japanese Clinical Practice Guideline for Acute Kidney Injury [4] [ABSTRACT FROM AUTHOR]

Background: Regional citrate anticoagulation (RCA) for the prevention of clotting of the extracorporeal blood circuit during continuous kidney replacement therapy (CKRT) has been employed in limited fashion because of the complexity and complications associated with certain protocols. Hypertonic citrate infusion to achieve circuit anticoagulation results in variable systemic citrate- and sodium load and increases the risk of citrate accumulation and hypernatremia. The practice of "single starting calcium infusion rate for all patients" puts patients at risk for clinically significant hypocalcemia if filter effluent calcium losses exceed replacement. A fixed citrate to blood flow ratio, personalized effluent and pre-calculated calcium infusion dosing based on tables derived through kinetic analysis enable providers to use continuous veno-venous hemo-diafiltration (CVVHDF)-RCA in patients with liver citrate clearance of at least 6 L/h.Methods: This was a single-center prospective observational study conducted in intensive care unit patients triaged to be treated with the novel pre-calculated CVVHDF-RCA "Non-shock" protocol. RCA efficacy outcomes were time to first hemofilter loss and circuit ionized calcium (iCa) levels. Safety outcomes were surrogate of citrate accumulation (TCa/iCa ratio) and the incidence of acid-base and electrolyte complications.Results: Of 53 patients included in the study, 31 (59%) had acute kidney injury and 12 (22.6%) had the diagnosis of cirrhosis at the start of CVVHDF-RCA. The median first hemofilter life censored for causes other than clotting exceeded 70 h. The cumulative incidence of hypernatremia (Na > 148 mM), metabolic alkalosis (HCO3- > 30 mM), hypocalcemia (iCa < 0.9 mM) and hypercalcemia (iCa > 1.5 mM) were 1/47 (1%), 0/50 (0%), 1/53 (2%), 1/53 (2%) respectively and were not clinically significant. The median (25th-75th percentile) of the highest TCa/iCa ratio for every 24-h interval on CKRT was 1.99 (1.91-2.13).Conclusions: The fixed citrate to blood flow ratio, as opposed to a titration approach, achieves adequate circuit iCa (< 0.4 mm/L) for any hematocrit level and plasma flow. The personalized dosing approach for calcium supplementation based on pre-calculated effluent calcium losses as opposed to the practice of "one starting dose for all" reduces the risk of clinically significant hypocalcemia. The fixed flow settings achieve clinically desirable steady state systemic electrolyte levels. [ABSTRACT FROM AUTHOR]

Background: The objectives of the study are to describe tandem therapeutic plasma exchange (TPE) and continuous kidney replacement therapy (CKRT) patients' outcomes in a large institution. Methods: We reviewed pediatric patients receiving tandem TPE and CKRT from 2013 to 2016. Over the study period, 63 discrete patients received tandem TPE and CKRT for a total of 378 TPE procedures on 1676 days on CKRT. Results: Patient age ranged from newborn to 19 years old with weights ranging from 2.31 to 112.3 kg (17 patients were < 10 kg and less than 1 year old). All procedures were completed in intensive care units (ICU) as CKRT can only be done in this environment. All treatments completed successfully; majority of patients (90%) developed hypocalcemia though none were symptomatic. Case mortality rate was 40%. Disease severity scores at ICU admission were higher and time to TPE and CKRT start was longer in the deceased group. Conclusions: As a conclusion, though complications including hypocalcemia are common with tandem TPE and CKRT in pediatrics, patients remained asymptomatic. Such treatments have to be carefully planned with interdisciplinary teams to address indications, technicalities, and complications. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common complication of critically ill adult patients with COVID-19. However, currently, no studies investigate kidney impairment in children with COVID-19. We investigated incidence and treatment of AKI in pediatric patients with COVID-19 in Wuhan Children's Hospital during the early stages of the COVID-19 pandemic and discuss possible mechanisms of AKI related to SARS-CoV-2 infection. Methods: By extracting data from electronic medical records, we conducted a retrospective observational study of kidney involvement in confirmed pediatric COVID-19 cases in Wuhan Children's Hospital during the coronavirus outbreak, from January 24 to March 20, 2020. Clinical presentations, clinical courses, laboratory findings, and medical interventions are described below. Results: Among 238 confirmed COVID-19 cases, only three were critically ill and needed intensive care unit (ICU) admission. All three developed AKI, but AKI was not detected in any non-critically ill patients outside the ICU. Two of the three patients with AKI had prodromal gastrointestinal symptoms. Significantly elevated interleukin-6 (IL-6) levels and complement activation were observed in these patients with AKI. The three patients with AKI were treated with plasma exchange (PE) and continuous kidney replacement therapy (CKRT), resulting in one complete recovery, one partial recovery, and one mortality due to critical illness. Conclusions: Critically ill children with COVID-19 may develop AKI, especially following prodromal gastrointestinal symptoms. An inflammatory storm and complement-mediated injury may underlie AKI development in children with COVID-19. Our study supports implantation of PE and CKRT in management of critically ill patients with AKI. [ABSTRACT FROM AUTHOR]

Background: Continuous kidney replacement therapy (CKRT) is a common modality for treatment of severe acute kidney injury (AKI) in children. Adult technologies routinely utilized to provide this therapy have a large extracorporeal volume. The Prismaflex™ HF20 filter set has a relatively low extracorporeal blood volume of 60 mL, which provides technological benefit for smaller children compared with current filter sets available in the USA. Methods: We conducted a multicenter, open-label single group study to evaluate whether the Prismaflex™ HF20 filter set delivers efficacious and safe CKRT to support patients with AKI, fluid overload, or both in pediatric patients weighing ≥ 8 to 20 kg. Results: Twenty-three patients were enrolled between April 24, 2016 and April 8, 2018. The mean reduction in blood urea nitrogen from baseline to 24 h was 58.12 ± 20.08% (95% CI, − 68.45 and − 47.79 (p = 0.0008)). Median cumulative normalized effluent rate at 24 h was 60.8 mL/kg/h (25.9, 83.7). None of the patients participating in the study suffered a serious adverse event; thus, no obvious safety concerns were noted. Conclusions: We suggest that the Prismaflex HF20™ filter set used in conjunction with the Prismaflex™ System Software Version 7.10 or 7.20 is a suitable alternative to larger filter sets for use in pediatric patients weighing less than 20 kg. [ABSTRACT FROM AUTHOR]

Rationale & Objective: Continuous kidney replacement therapy (CKRT) is the predominant form of acute kidney replacement therapy used for critically ill adult patients with acute kidney injury (AKI). Given the variability in CKRT practice, a contemporary understanding of its epidemiology is necessary to improve care delivery., Study Design: Multicenter, prospective living registry., Setting & Population: 1,106 critically ill adults with AKI requiring CKRT from December 2013 to January 2021 across 5 academic centers and 6 intensive care units. Patients with pre-existing kidney failure and those with coronavirus 2 infection were excluded., Exposure: CKRT for more than 24 hours., Outcomes: Hospital mortality, kidney recovery, and health care resource utilization., Analytical Approach: Data were collected according to preselected timepoints at intensive care unit admission and CKRT initiation and analyzed descriptively., Results: Patients' characteristics, contributors to AKI, and CKRT indications differed among centers. Mean (standard deviation) age was 59.3 (13.9) years, 39.7% of patients were women, and median [IQR] APACHE-II (acute physiologic assessment and chronic health evaluation) score was 30 [25-34]. Overall, 41.1% of patients survived to hospital discharge. Patients that died were older (mean age 61 vs. 56.8, P  < 0.001), had greater comorbidity (median Charlson score 3 [1-4] vs. 2 [1-3], P < 0.001), and higher acuity of illness (median APACHE-II score 30 [25-35] vs. 29 [24-33], P  = 0.003). The most common condition predisposing to AKI was sepsis (42.6%), and the most common CKRT indications were oliguria/anuria (56.2%) and fluid overload (53.9%). Standardized mortality ratios were similar among centers., Limitations: The generalizability of these results to CKRT practices in nonacademic centers or low-and middle-income countries is limited., Conclusions: In this registry, sepsis was the major contributor to AKI and fluid management was collectively the most common CKRT indication. Significant heterogeneity in patient- and CKRT-specific characteristics was found in current practice. These data highlight the need for establishing benchmarks of CKRT delivery, performance, and patient outcomes. Data from this registry could assist with the design of such studies., (© 2023 The Authors.)

The utilization of kidney replacement therapies (KRT) for fluid management of patients who are critically ill has significantly increased over the last years. Clinical studies have suggested that both fluid accumulation and high fluid removal rates are associated with adverse outcomes in the critically ill population receiving KRT. Importantly, the ideal indications and/or fluid management strategies that could favorably affect these patients are unknown; however, differentiating clinical scenarios in which effective fluid removal may provide benefit to the patient by avoiding congestive organ injury, compared with other settings in which this intervention may result in harm, is direly needed in the critical care nephrology field. In this review, we describe observational data related to fluid management with KRT, and examine the role of point-of-care ultrasonography as a potential tool that could provide physiologic insights to better individualize decisions related to fluid management through KRT., Competing Interests: W. Beaubien-Souligny reports receiving honoraria from Baxter, and being employed by Centre Hospitalier de l'Université de Montréal (CHUM). J.A. Neyra reports serving as guest editor and on the editorial board of Advances in Chronic Kidney Disease, as section editor of Clinical Nephrology, as guest editor of Critical Care Nephrology, and on the editorial board of Kidney360; having consultancy agreements with Baxter Healthcare Inc., Biomedical Insights, and Leadiant Biosciences; and being employed by the University of Alabama at Birmingham. The remaining author has nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Continuous kidney replacement therapy is commonly used in the critically ill population. Despite the recent development in continuous kidney replacement therapy technology and clinical informatics, many aspects of continuous kidney replacement therapy delivery are still not fully standardized, and quality assurance programs for the provision of continuous kidney replacement therapy are not fully developed. This is in part explained by practice variations, suboptimal integration between machine and clinical data, and the lack of validated continuous kidney replacement therapy quality indicators that are feasible for measurement and monitoring. The further development and sustainable implementation of quality assurance systems that support continuous kidney replacement therapy delivery rely on the collaborative work of the critical care nephrology community and the continuous evolution of clinical informatics. In this article, we describe the present status of information technology and quality assurance systems for continuous kidney replacement therapy delivery and provide a framework for technology development and implementation which is in the pipeline of enhanced continuous kidney replacement therapy delivery., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Regional citrate anticoagulation (RCA) is not recommended in patients with shock or severe liver failure. We designed a protocol with personalized precalculated flow settings for patients with absent citrate metabolism that abrogates risk of citrate toxicity, and maintains neutral continuous KRT (CKRT) circuit calcium mass balance and normal systemic ionized calcium levels., Methods: A single-center prospective cohort study of patients in five adult intensive care units triaged to the CVVHDF-RCA "Shock" protocol., Results: Of 31 patients included in the study, 30 (97%) had AKI, 16 (52%) had acute liver failure, and five (16%) had cirrhosis at the start of CKRT. The median lactate was 5 mmol/L (interquartile range [IQR], 3.2-10.7), AST 822 U/L (IQR, 122-2950), ALT 352 U/L (IQR, 41-2238), total bilirubin 2.7 mg/dl (IQR, 1.0-5.1), and INR two (IQR, 1.5-2.6). The median first hemofilter life censored for causes other than clotting exceeded 70 hours. The cumulative incidence of hypernatremia (Na >148 mM), metabolic alkalosis (HCO3- >30 mM), and hypophosphatemia ( P <2 mg/dl) were one out of 26 (4%), zero out of 30 (0%), and one out of 30 (3%), respectively, and were not clinically significant. Mild hypocalcemia occurred in the first 4 hours in two out of 31 patients, and corrected by hour 6 with no additional Ca supplementation beyond the per-protocol administered Ca infusion. The maximum systemic total Ca (tCa; mM)/ionized Ca (iCa; mM) ratio never exceeded 2.5., Conclusions: The Shock protocol can be used without contraindications and is effective in maintaining circuit patency with a high, fixed ACDA infusion rate to blood flow ratio. Keeping single-pass citrate extraction on the dialyzer >0.75 minimizes the risk of citrate toxicity even in patients with absent citrate metabolism. Precalculated, personalized dosing of the initial Ca-infusion rate from a table on the basis of the patient's albumin level and the filter effluent flow rate maintains neutral CKRT circuit calcium mass balance and a normal systemic iCa level., Competing Interests: M. Heung reports consultancy agreements with Baxter Inc, Potrero Medical Inc., and Wolters Kluwer (Lexicomp); reports receiving research funding from Centers for Disease Control, Patient-Centered Outcomes Research Institute, and Veterans Affairs; reports receiving honoraria from National Kidney Foundation; and is a scientific advisor or member of Associate Editor/Editorial board, Advances in CKD. D. Humes reports consultancy agreements with SeaStar Medical; having an ownership interest in Innovative BioTherapies, Inc. and SeaStar Medical, Inc.; reports receiving research funding from Innovative Biotherapies, Lowell Pharmaceuticals, Renal Research Institute, SeaStar Medical, and Sygin; reports being a scientific advisor or member of Innovative Biotherapies and SeaStar Medical. B. Szamosfalvi reports receiving research funding from Renal Research Institute. B. Wagner reports having an ownership interest in Able-Wagner, Inc. L. Yessayan reports receiving research funding from renal research institute and being a Section Editor for ASAIO Journal, Renal\Extracorporeal Blood Treatment. R. Sohaney reports being funded by a training grant from the National Institutes of Health (5T32DK007378-40). All remaining authors have nothing to disclose., (Copyright © 2021 by the American Society of Nephrology.)