Continuous Replacement Research Articles

Study protocol for a consortium linking health medical records, biospecimens, and biosignals in Korean patients with acute kidney injury (LINKA cohort).

Acute kidney injury (AKI) may transition into acute kidney disease (AKD) or chronic kidney disease (CKD), leading to subacute and chronic deterioration, respectively. Despite extensive research on AKI, a significant gap exists in understanding the specific biomarkers and development of individualized treatments prior to progression to AKD and CKD. As a consortium linking health medical records, biospecimens, and biosignals, eight Korean tertiary hospitals participated in the establishment of a retrospective and prospective cohort, each comprising approximately 1,500 patients with AKI receiving continuous kidney replacement therapy (CKRT). Other information included AKI-related information, CKRT prescriptions, and patient outcomes. Follow-up timeframes were set at baseline, 1 week, 3 months, and 1 year after the initiation of CKRT. Human biospecimens will be collected from the prospective cohort. An artificial intelligence model was developed using the retrospective cohort to predict the prognosis of AKD and its subsequent sequelae and to formulate patient-individualized treatments, with validation planned in a prospective cohort. Follow-up studies are scheduled to identify biomarkers related to outcomes using biospecimens. Finally, based on the results and literature review, decision-making on the prevention and management of diseases, as well as the development of treatment guidelines, are being planned. This study will provide scientific evidence on clinical insights and appropriate management targets for AKI and AKD, which will form the basis for relevant treatment guidelines. Additionally, these findings may facilitate a more personalized approach to patient care, enabling clinicians to tailor treatments based on individual biomarker profiles and predictive models.

Dynamic Data-Driven Deterioration Model for Sugarcane Shredder Hammers Oriented to Lifetime Extension

Several sugar mills operate as waste-to-energy plants. The shredder is the initial high-energy machine in the production chain and prepares sugarcane. Its hammers, essential spare parts, require continuous replacement. Then, the search for intelligent strategies to extend the lifetime of these hammers is fundamental. This paper presents (a) a dynamic data-driven model for estimating the deterioration and predicting remaining life of the sugarcane shredder hammers during operation, for which the real data of the entering sugarcane flow and the power required to prepare the sugarcane are analyzed, and (b) a management architecture intended for online decision-making assistance to extend the hammers’ life by making a trade-off between the desired lifetime, along with a nominal shredder work satisfaction criterion. The deterioration model is validated with real data achieving an accuracy of 84.41%. The remaining life prognostic is within a confidence zone calculated from the historical sugarcane flow, with a probability close to 99%, fitting a lognormal probability distribution. A numerical example is also provided to illustrate a closed loop control, where the proposed architecture is used to extend the useful life of the hammers during operation, adjusting the incoming sugarcane flow while maintaining the nominal work satisfaction of the shredder.

Albumin and platelet loss during the application of CytoSorb® in critically ill patients: a post-hoc analysis of the Cyto-SOLVE trial.

Adsorption devices like CytoSorb® (CS) are increasingly used in critically ill patients. However, potential adverse effects have not been sufficiently investigated. The aim of this post-hoc analysis of the monocentric prospective Cyto-SOLVE study was to examine albumin concentration and platelet count during the application of CS in intensive care unit (ICU) patients with different indications for CS therapy. 29 Adult ICU patients receiving continuous kidney replacement therapy and CS application for 12 hours were included. Albumin concentration and platelet count were measured before, during, and after application. Changes in albumin concentration and platelet count were investigated. Since 10/29 patients were substituted with platelets during CS therapy and 20/29 received albumin, subgroup analysis was performed in patients receiving no platelet concentrate and <20g albumin substitution during CS application. The dependent sample t-test was used to detect significant (p<0.05) changes over time and multivariate models were investigated. We observed a significant reduction in platelets (p=0.005, mean 14 G/l, 95% confidence interval (CI) 4 - 23G/l) during CS therapy with an even more pronounced drop in those 19 patients without platelet substitution (p=0.001, mean 22G/l, 95% CI 10 - 34). No significant change was detected in the albumin concentration of all patients. However, a significant albumin decrease was observed in those 17 patients with less than 20g albumin substitution during CS therapy (p=0.007, mean 0.17g/dL, 95% CI 0.05 - 0.29). No other potential covariates for the decrease could be identified in a multivariate model. Since a drop in albumin and platelets occurred during the use of CS, an increased substitution might be necessary. Knowledge of potential side effects is of great importance to prevent harm during the use of extracorporeal procedures. This knowledge should be considered for a reliable risk-benefit assessment in the future.

Fluid Overload in Children Following Hematopoietic Cell Transplant: A Comprehensive Review.

Fluid overload significantly increases morbidity and mortality in critically ill children. Following hematopoietic cell transplant (HCT), children are at a high risk of fluid accumulation due to essential increased fluid intake for nutrition, blood products, and antimicrobials. In addition, many complications predispose these children to capillary leak and fluid overload (FO), such as sinusoidal obstruction syndrome, engraftment syndrome, sepsis, and acute kidney injury (AKI). FO > 10% occurs in nearly half of children following HCT and is associated with a lower PICU survival rate. In addition, in children with acute respiratory failure post HCT, each 1% increase in cumulative fluid balance on d 3 increases the odds of PICU mortality by 3%. Furthermore, FO worsens AKI. Tools such as the renal angina index and urinary biomarkers such as neutrophil gelatinase-associated lipocalin can help identify patients at risk of AKI and FO. Early detection, prevention, and intervention are crucial to improving outcomes in this population. Management strategies include fluid restriction, diuretics, and continuous kidney replacement therapy (CKRT) when FO exceeds 10% and other measures have failed.

Encapsulation of Dexamethasone into mRNA–Lipid Nanoparticles Is a Promising Approach for the Development of Liver-Targeted Anti-Inflammatory Therapies

The objective of this study was to develop two lipid nanoparticle (LNP) formulations capable of efficiently expressing a reporter mRNA while co-delivering the anti-inflammatory drug dexamethasone (DX) to reduce inflammatory side effects in protein replacement therapies. Two types of LNPs were developed, in which 25% of cholesterol was replaced by DX. These LNPs contained either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as a helper lipid. The resulting LNPs exhibited high stability, homogeneity, and near-neutral Zeta potentials. SAXS experiments confirmed DX incorporation into the LNP core, with slow in vitro DX release observed over 48 h. The LNPs achieved high mRNA encapsulation efficiency (95–100%) and effectively transfected HepG2 cells, dendritic cells, and hPBMCs. While LNPs increased cytokine release (IL-1β, TNF-α, MCP-1), LNPs-DX significantly reduced cytokine levels, demonstrating enhanced anti-inflammatory properties while maintaining mRNA expression levels. In vivo biodistribution showed predominant liver localization post-intramuscular injection, regardless of the DSPC or DOPE composition. LNPs co-loaded with mRNA and DX are promising candidates for continuous protein replacement. Due to their ability to reduce treatment-related inflammation while maintaining significant mRNA expression levels, these LNPs are perfectly suited for the treatment of liver-related metabolic diseases.

Intensive care unit continuous kidney replacement therapy: time to change dosage recommendations?

Continuous kidney replacement therapy (CKRT) is the predominant form of acute kidney support used for hemodynamically unstable adult ICU patients with severe AKI (KDIGO stage 3). The success of CKRT depends on the achieved doses. Practice patterns worldwide are highly variable. A contemporary understanding of treatment adequacy is essential. The KDIGO AKI clinical guidelines recommend delivering effluent volumes of 20-25ml/kg/hour for CKRT in the ICU setting, with the caveat that higher prescribed doses (25-30ml(kg/h) may be necessary to achieve adequate delivered CKRT doses. The reference landmark trials provide definitive evidence that increases of delivered CKRT doses beyond the recommended dose are not beneficial for unselected ICU patients with severe AKI. However, the minimum delivered CKRT intensity at which underdosing becomes harmful remains unknown. The answer to this question has clinical relevance (dosing of critically ill patients with obesity or Covid-19 disease, minimizing adverse effects of CKRT) and a relevant impact on the costs of CKRT. The delivered dose of CKRT for Japanese ICU patients with severe AKI has been generally smaller (median 15ml/h/kg) than the recommended delivered KDIGO dose. The most recently published retrospective cohort study by Okamoto et al. demonstrated that low delivered CKRT doses were associated with a higher mortality among critically ill patients with severe AKI. These data challenge the nation-wide accepted hypothesis that a lower limit of delivered CKRT (< 20ml/ kg/h) may adequately control uremia/volume overload. Thus, there is an unmet clinical need for prospective randomized trials defining the minimal effective dose of CKRT. Given the dynamic nature of the precipitating critical illness and the natural course of most episodes of AKI, CKRT dose targets are likely to vary. Doses should be tailored to the needs of the individual patient within the limits of the KDIGO guideline recommendations. The Japanese experience with low-dose CKRT is not practice changing.

Development of a Nomogram for Predicting ICU Readmission.

Background This study aims to develop and validate a comprehensive prediction model for ICU readmissions. Readmission following ICU discharge is associated with adverse outcomes such as increased mortality, prolonged hospital stays, and elevated healthcare costs. Consequently, predicting and preventing readmissions is crucial. Previous models for predicting ICU readmissions were primarily based on physiological indices; however, these indices fail to capture the complete nature of treatment or patient conditions beyond physiological measures, thereby limiting the accuracy of these predictions. Methodology A total of 1,400 patients who had an unplanned ICU admission at Sapporo Medical University Hospital from January 2015 to October 2022 were included; a single regression analysis was performed using unplanned ICU readmission as the dependent variable. After performing a single regression analysis, logistic regression analysis using the stepwise method was performed using variables with significant differences, and a predictive nomogram was created using the variables that remained in the final model. To internally validate the predictive nomogram model, nonparametric bootstrapping (1,000 replications) was performed on the original model. Results Of the 1,400 patients who had an unplanned admission to the ICU, 114 (8.1%) were readmitted to the ICU unplanned. Seven main variables (Sequential Organ Failure Assessment score, respiratory rate, Glasgow Coma Scale, sleep disturbance, Continuous Kidney Replacement Therapy, presence of tracheal suctioning, and Oxygen Saturation) were selected to be associated with ICU readmission. The evaluation of the models showed excellent discrimination with an area under the receiver operating characteristic of 0.805 (original model) and 0.796 (bootstrap model). Calibration plots also confirmed good agreement between observed and predicted reentry. Conclusions This new predictive model is more accurate than previous models because it includes physiological indicators as well as other patient conditions and procedures needed and is expected to be used in clinical practice. In particular, the inclusion of new factors, such as sleep disturbance and the need for tracheal suctioning, enabled a more comprehensive patient assessment. The use of this predictive nomogram as a criterion for discharging ICU patients may prevent unplanned ICU readmission.

Monte Carlo simulations of cefepime in children receiving continuous kidney replacement therapy support continuous infusions for target attainment

BackgroundSepsis 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.MethodsWe 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.ResultsAssuming 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.ConclusionsOur 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.

Optimizing Intracranial Pressure Management in AKI: A Novel Approach Using Enhanced Sodium Concentration in Continuous Kidney Replacement Therapy

Optimizing Intracranial Pressure Management in AKI: A Novel Approach Using Enhanced Sodium Concentration in Continuous Kidney Replacement Therapy

Multidisciplinary Inter-rater Reliability of Muscle Ultrasonography in Patients with AKI Requiring Continuous Kidney Replacement Therapy

Multidisciplinary Inter-rater Reliability of Muscle Ultrasonography in Patients with AKI Requiring Continuous Kidney Replacement Therapy

Oxiris Membrane Performance in Patients with Septic Shock and Continuous Kidney Replacement Therapy Requirement: A Randomized Controlled Trial

Oxiris Membrane Performance in Patients with Septic Shock and Continuous Kidney Replacement Therapy Requirement: A Randomized Controlled Trial

Successful Use of Droxidopa to Treat Intractable Hypotension Attributed to Vasodilatory Shock Due to Autonomic Failure in a Patient with ESKD Who Is Dependent on Continuous Kidney Replacement Therapy

Successful Use of Droxidopa to Treat Intractable Hypotension Attributed to Vasodilatory Shock Due to Autonomic Failure in a Patient with ESKD Who Is Dependent on Continuous Kidney Replacement Therapy

Machine-Learning Model for Predicting Early Mortality in Critically Ill Patients Requiring Continuous Kidney Replacement Therapy

Machine-Learning Model for Predicting Early Mortality in Critically Ill Patients Requiring Continuous Kidney Replacement Therapy

Comparison of Conventional and High-Dose Continuous Kidney Replacement Therapy in Critically Ill Patients with Septic AKI

Comparison of Conventional and High-Dose Continuous Kidney Replacement Therapy in Critically Ill Patients with Septic AKI

Use of Vasopressors in Patients with AKI on Continuous Kidney Replacement Therapy

Use of Vasopressors in Patients with AKI on Continuous Kidney Replacement Therapy

Impacts of Skeletal Muscle Mass and Quality on Kidney Recovery after AKI Receiving Continuous Kidney Replacement Therapy

Impacts of Skeletal Muscle Mass and Quality on Kidney Recovery after AKI Receiving Continuous Kidney Replacement Therapy

Towards a Greener Practice: Implementation of Continuous Kidney Replacement Therapy Waste Reduction

Towards a Greener Practice: Implementation of Continuous Kidney Replacement Therapy Waste Reduction

Hypotension at Initiation of Continuous Kidney Replacement Therapy: A Harbinger of Poor Outcomes

Hypotension at Initiation of Continuous Kidney Replacement Therapy: A Harbinger of Poor Outcomes

Troponin Clearance via Continuous Kidney Replacement Therapies in the Intensive Care Unit (ICU)

Troponin Clearance via Continuous Kidney Replacement Therapies in the Intensive Care Unit (ICU)

Correlation between Ionized and Total Magnesium in Children on Continuous Kidney Replacement Therapy

Correlation between Ionized and Total Magnesium in Children on Continuous Kidney Replacement Therapy