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Introduction: At the time of renal replacement therapy, approximately 20% of critically ill patients have septic shock. In this study, medium cutoff (MCO) continuous venovenous hemodialysis (CVVHD) was compared to high-flux membrane continuous venovenous hemodiafiltration (CVVHDF) in terms of hemodynamic improvement, efficiency, middle molecule removal, and inflammatory system activation., Methods: This is a monocenter crossover randomized study. Between December 31, 2017, and December 31, 2019, 20 patients with septic shock and stage 3 acute kidney injury (AKI) admitted to 2 Italian ICUs were enrolled. All patients underwent CVVHD with Ultraflux® EMiC®2 and CVVHDF with AV1000S® without washout. Each treatment lasted 24 h., Results: Compared to AV1000S®-CVVHDF, EMIC®2-CVVHD normalized cardiac index (β = -0.64; p = 0.02) and heart rate (β = 5.72; p = 0.01). Interleukin-8 and myeloperoxidase removal were greater with AV1000S®-CVVHDF than with EMiC®2-CVVHD (β = 0.35; p < 0.001; β = 0.43; p = 0.03, respectively). Leukocytosis improved over 24 h in EMiC®2-CVVHD-treated patients (β = 4.13; p = 0.03), whereas procalcitonin levels decreased regardless of the modality (β = 0.89; p = 0.01) over a 48-h treatment period. Reduction rates, instantaneous plasmatic clearance of urea, creatinine, and β2-microglobulin were similar across modalities. β2-Microglobulin removal efficacy was greater in the EMiC®2 group (β = 0-2.88; p = 0.002), while albumin levels did not differ. Albumin was undetectable in the effluent in both treatments., Discussion: In patients with septic shock and severe AKI, the efficacy of uremic toxin removal was comparable between MCO-CVVHD and CVVHDF. Further, MCO-CVVHD was associated with improved hemodynamics. Fraction of filtration and transmembrane pressure reduction and the maintenance of equal efficacy might be the key features of CVVHD with MCO membranes in critically ill patients., (© 2022 S. Karger AG, Basel.)

Sepsis-induced acute kidney injury (AKI) is a frequent complication in critically ill patients, refractory to conventional treatments. Aberrant activation of innate immune system may affect organ damage with poor prognosis for septic patients. Here, we investigated the efficacy of polymethyl methacrylate membrane (PMMA)-based continuous hemofiltration (CVVH) in modulating systemic and tissue immune activation in a swine model of LPS-induced AKI. After 3 h from LPS infusion, animals underwent to PMMA-CVVH or polysulfone (PS)-CVVH. Renal deposition of terminal complement mediator C5b-9 and of Pentraxin-3 (PTX3) deposits were evaluated on biopsies whereas systemic Complement activation was assessed by ELISA assay. Gene expression profile was performed from isolated peripheral blood mononuclear cells (PBMC) by microarrays and the results validated by Real-time PCR. Endotoxemic pigs presented oliguric AKI with increased tubulo-interstitial infiltrate, extensive collagen deposition, and glomerular thrombi; local PTX-3 and C5b-9 renal deposits and increased serum activation of classical and alternative Complement pathways were found in endotoxemic animals. PMMA-CVVH treatment significantly reduced tissue and systemic Complement activation limiting renal damage and fibrosis. By microarray analysis, we identified 711 and 913 differentially expressed genes with a fold change >2 and a false discovery rate <0.05 in endotoxemic pigs and PMMA-CVVH treated-animals, respectively. The most modulated genes were Granzyme B, Complement Factor B, Complement Component 4 Binding Protein Alpha, IL-12, and SERPINB-1 that were closely related to sepsis-induced immunological process. Our data suggest that PMMA-based CVVH can efficiently modulate immunological dysfunction in LPS-induced AKI., Competing Interests: GC reports research grant donation from TORAY (Toray Industries, Inc), during the conduct of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Stasi, Franzin, Divella, Sallustio, Curci, Picerno, Pontrelli, Staffieri, Lacitignola, Crovace, Cantaluppi, Medica, Ronco, de Cal, Lorenzin, Zanella, Pertosa, Stallone, Gesualdo and Castellano.)

The urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]∙[IGFBP7]) have been introduced to improve risk prediction of severe acute kidney injury (AKI) within 12 hours of measurement. We performed a prospective cohort study to evaluate if the predictive value of [TIMP-2]∙[IGFBP7] for AKI might continue after 12 hours. We enrolled 442 critically ill adult patients from June to December 2016. Urine samples were collected at admission for [TIMP-2]∙[IGFBP7] measurement. Baseline patient characteristics were recorded including patients' demographics, prior health history, and the main reason for admission to build a logistic regression model to predict AKI. AKI occurrence differed between patients with [TIMP-2]∙[IGFBP7] ≤0.3 and >0.3 (ng/ml) 2 /1000 (31.9% and 68.10% respectively; p < 0.001). Patients with AKI had higher biomarker values compared to those without AKI (0.66 (0.21-2.84) vs 0.22 (0.08-0.63) (ng/ml) 2 /1000; p < 0.001). [TIMP-2]∙[IGFBP7] at ICU admission had a lower performance in predicting AKI at any stage within 48 hours and 7 days after measurement (area under the receiver operating characteristic curve (AUC) equal to 0.70 (95%CI 0.65-0.76), AUC 0.68 (95%CI 0.63-0.73)). In the logistic regression model, 0.1 (ng/ml) 2 /1000-unit increment was likely to increase the risk of AKI by 2% (p = 0.002).

AKI is associated with increased risk of death, prolonged length of stay and development of de-novo chronic kidney disease. The aim of our study is the development and validation of prediction models to identify the risk of AKI in ICU patients up to 7 days. We retrospectively recruited 692 consecutive patients admitted to the ICU at San Bortolo Hospital (Vicenza, Italy) from 1 June 2016 to 31 March 2017: 455 patients were treated as the derivation group and 237 as the validation group. Candidate variables were selected based on a literature review and expert opinion. Admission eGFR< 90 ml/min /1.73 mq (OR 2.78; 95% CI 1.78-4.35; p<0.001); SOFAcv ≥ 2 (OR 2.23; 95% CI 1.48-3.37; p<0.001); lactate ≥ 2 mmol/L (OR 1.81; 95% CI 1.19-2.74; p = 0.005) and (TIMP-2)•(IGFBP7) ≥ 0.3 (OR 1.65; 95% CI 1.08-2.52; p = 0.019) were significantly associated with AKI. For the q-AKI score, we stratified patients into different AKI Risk score levels: 0-2; 3-4; 5-6; 7-8 and 9-10. In both cohorts, we observed that the proportion of AKI patients was higher in the higher score levels., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: CR received compensation from Astute Medical, OCD, Asahi Medical, Baxter, and Toray Medical. AB is the founder, development manager and scientific referent of abcGo s.r.l. AMT is an employee and received compensation in the form of a salary from the RTS Colombia subsidiary of Baxter International. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials

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.

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.)

Renal replacement therapy (RRT) is a form of extracorporeal support for critical patients, especially for those with acute kidney injury. This therapy enables to gain adequate control over the great metabolic and fluids demand when kidneys are not able to do so; this condition is habitually present in patients who are admitted to intensive care units. However, it is also clear that these patients present a higher mortality rate and, in some cases, complications associated with the therapy. Therefore, it is fundamental to optimize and customize different aspects of RRT that range from the ideal timing including the modality and the dose until its suspension or ending. There currently is a great deal of controversy in all of these RRT-related topics. Although different predictive models have been proposed to determine the optimal timing of therapy discontinuation, nowadays urine output, serum and urine creatinine levels are perhaps the only variables associated with effective discontinuation. Future studies should focus on more accurately predicting renal recovery. This review provides an approach based on current evidence regarding effective discontinuation., (© 2018 S. Karger AG, Basel.)

For continuous renal replacement therapy (CRRT), the extracorporeal filter provides solute depuration, fluid removal, and control of electrolyte and acid-base balance in critically ill patients with acute kidney injury (AKI). The membranes comprising CRRT filters are almost exclusively based on hollow fiber designs and, while adapted from the chronic hemodialysis field, have features that are specific to the requirements of CRRT nevertheless. In addition, these devices have evolved through the 40 years of CRRT in response to changes in clinical practice and the desire to extend the solute removal spectrum. For some critically ill patients, more targeted removal of specific compounds poorly cleared by standard CRRT can be attempted with techniques based on adsorption. Sorbent hemoperfusion is now being applied more broadly in critically ill patients, especially in those with sepsis and systemic inflammation. In this review, the manner in which CRRT membranes and extracorporeal sorbents have evolved over the past 40 years for the treatment of critically ill patients with AKI and other disorders is described., (© 2018 S. Karger AG, Basel.)

Purpose: Dialysis is a highly quantitative therapy involving large volumes of both clinical and technical data. While automated data collection has been implemented for chronic dialysis, this has not been done for acute kidney injury patients treated with continuous renal replacement therapy (CRRT)., Methods: After a brief review of the fundamental aspects of electronic medical records (EMRs), a new tool designed to provide clinicians with individualized CRRT treatment data is analyzed, with emphasis on its quality assurance capabilities., Results: The first platform addressing the problem of data collection and management with current CRRT machines (Sharesource system; Baxter Healthcare) is described. The system provides connectivity for the Prismaflex CRRT machine and enables both EMR connectivity and therapy analytics with 2 basic components: the connect module and the report module., Conclusions: The enormous amount of data in CRRT should be collected and analyzed to enable adequate clinical decisions. Current CRRT technology presents significant limitations with consequent lack of rigorous analysis of technical data and relevant feedback. From a quality assurance perspective, these limitations preclude any systematic assessment of prescription and delivery trends that may be adversely affecting clinical outcomes. A detailed assessment of current practice limitations is provided together with several possible ways to address such limitations by a new technical tool.

Introduction: One of the top research priorities in acute kidney injury is related to the timing of renal replacement therapy (RRT) initiation. The purpose was to develop an index that might serve as a standardized concept of timing of initiation of RRT., Methods: A previously described database was used. We applied a multivariable Cox regression model with backward selection to characterize parameters present in those patients who received RRT compared with those who did not receive RRT., Results: We studied 590 patients. We identified independent risk factors for RRT and a risk score was devised. The Area Under the Curve of the receiver operating characteristic curve was 0.81 (95% CI 0.74-0.86) for predicting the need for RRT., Conclusions: We have developed a simple Score (IRRIV Score) to identify patients at high risk of requiring RRT. This score may serve as a standardized definition of the timing of initiation of RRT., (© 2015 S. Karger AG, Basel)