Use of Fluoride as a Marker Solute to Quantify the Current Effective Delivered Dose in Continuous Renal Replacement Therapy: An "in vitro" Study.

BACKGROUND: The current effective delivered dose is a quality indicator for continuous renal replacement therapy. Its periodic assessment might enable physicians to deliver personalised treatments. Yet, its quantification as by extracorporeal urea clearance (Cl) is cumbersome and thus often neglected in routine practice. The aim of this in vitro study is to demonstrate the non-inferior effectiveness of assessing the current effective delivered dose using a simpler, cheaper and faster approach based on measurement of fluoride rather than urea extracorporeal Cl. METHODS: We compared urea and fluoride removal in 3 post-dilution continuous veno-venous haemofiltration (CVVH) and 3 continuous veno-venous haemodialysis (CVVHD) in vitro experimental models. Experiments ran for 180 min, using 3 L of human blood, heparin anticoagulation and a machine dose of 30 mL/kg/h. Urea and fluoride were measured in the inflow, outflow and effluent lines to compare sieving coefficients (SC), saturation coefficients (SA) and transmembrane Cls. RESULTS: In CVVH, the median SC values were 1.06 (1.02-1.07) and 1.02 (1.01-1.04) for fluoride and urea, respectively (discrepancy of 4.3%), while transmembrane convective Cls were 31.28 (30.01-31.31) mL/kg/h and 30.30 (29-31.85) mL/kg/h (discrepancy of 3.13%), respectively. In CVVHD, the median SA values were 1.01 (0.96-1.02) and 1 (0.95-1.01) for fluoride and urea, respectively (discrepancy of 1.6%), while transmembrane dialytic Cls were 30.26 (29.52-31.32) mL/kg/h and 31.16 (30-31.75) mL/kg/h (discrepancy of -2.97%), respectively. CONCLUSION: Fluoride transmembrane removal was close to that observed with urea, in terms of SC, SA and transmembrane Cl. Fluoride seems as much accurate as urea in assessing the current effective delivered dose during both CVVH and CVVHD and might therefore be adopted for dose measurement. Besides accuracy, fluoride bedside assessment could present many advantages over urea, particularly in terms of availability, costs, time requirement and rapidity of assessment.

Choice of Catheter Size for Infants in Continuous Renal Replacement Therapy: Bigger Is Not Always Better.

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.

International Survey on the Management of Acute Kidney Injury and Continuous Renal Replacement Therapies: Year 2018.

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

Fluid Dynamics Analysis by CT Imaging Technique of New Sorbent Cartridges for Extracorporeal Therapies.

BACKGROUND: Recent innovations in biomaterials technology have led to the development of innovative sorbents adopted as adsorbing devices in the field of extracorporeal blood purification therapies. As removal mechanism, adsorption allows to remove specific molecules, selectively binding them to sorbent materials. In addition to the material properties, a quintessential aspect influencing device properties is blood flow distribution within the sorbent particles. OBJECTIVES: In order to adequately characterize the potential adsorbing properties for an effective blood purification therapy, an in vitro study assessing the fluid dynamics inside 3 new cartridges, HA130, HA230 and HA330 (Jafron, Zhuhai City, -China) was conducted through CT imaging technique. -Methods: The cartridges were placed in vertical position in the CT -gantry. Dye solution was circulated through the cartridges at 250 mL/min, longitudinal sections, 0.5 cm thick, were recorded for 60 s. Furthermore, an in vitro test was conducted to build pressure drop profiles. Blood was circulated at a different flow rate, 100-400 mL/min, step 50 mL/min. Pre and post cartridges pressures were acquired and pressure drop calculated. RESULTS: Sequential images demonstrated an excellent distribution of the flow inside the cartridges. Average flow velocity was 0.37 cm/s for the 3 cartridges. HA130 had a homogeneous flow profile along the entire length of the device; HA230 and HA330 showed minimal differences between central and peripheral regions. Pressure drop profiles resulted linear, increasing proportionally with blood flow rate and packing density. CONCLUSIONS: We may conclude that the structural and functional design of the studied cartridges is adequate for haemoperfusion with no channelling phenomena. This ensures maximum and optimal utilization of the sorbent contained in the devices.

oXirisNet Registry: A Prospective, National Registry on the oXiris Membrane.

Worldwide, the widespread use of extracorporeal blood purification therapies (EBPTs) is progressively increasing in everyday clinical practice, particularly in critical care settings. The efficacy of EBPTs on removal of inflammatory mediators is already well established in the literature. Nonetheless, clinical research is particularly cumbersome in this setting, and many clinical trials aiming at exploring the effect of EBPTs on outcomes have failed in demonstrating consistent results regarding 28-day- or hospital-mortality rates. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of EBPTs. The philosophy behind this Italian Registry is a renewal of the concept of "clinical research" in the field of EBPTs applied to critically ill, septic patients with or without acute kidney injury. The platform used for the registry - specifically designed for research purposes and fed by clinical data prospectively observed - promotes good practice with a positive and active interaction with the physician/researcher. This interaction has favorable real-time effects for the specific patient, providing "bed-side clinical feedbacks," similarly to the decision support system. Examples of these issues are bundles reminders, suggestions for drug adjustment according to the extracorporeal clearance, clinical calculator for body mass index, or mechanical ventilation setting. The platform-physician interaction has additional useful effects on the single utilizing center, providing "mid-term, center-specific clinical feedbacks." These generally consist of clusters of data taken over a certain period, for example, regarding patients' outcome, microbiological data, or use of disposable for EBPTs.

A New Series of Sorbent Devices for Multiple Clinical Purposes: Current Evidence and Future Directions.

Adsorption is an extracorporeal technique utilized for blood purification. It complements convection and diffusion (the main modalities of solute removal). It involves the passage of blood (or plasma) through an adsorption cartridge, where solutes are removed by direct binding to the sorbent material. Over the years, new adsorption cartridges, with improved characteristics have been developed. Furthermore, the therapeutic applications of adsorption have expanded. These now involve the treatment of inflammatory conditions, chronic uremic symptoms, and autoimmune disease, in addition to intoxication, which was once considered the classical indication for adsorption therapy. HA130, HA230, and HA330 (Jafron, Zhuhai City, China) are among the widely used adsorption cartridges in China. There has been sufficient body of evidence to support their effectiveness and safety. In this review, we aim to highlight their main clinical applications.

ACUsmart Continuous Renal Replacement Therapy Platform: Multicenter Pilot Study for Technical and Clinical Assessment (A.M.P. Study).

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.

Expanded haemodialysis: from operational mechanism to clinical results.

Recent advances in chemical composition and new production techniques resulted in improved biocompatibility and permeability of dialysis membranes. Among these, the creation of a new class of membranes called medium cut-off (MCO) represents an important step towards improvement of clinical outcomes. Such membranes have been developed to improve the clearance of medium to high molecular weight (MW) solutes (i.e. uraemic toxins in the range of 5-50 kDa). MCO membranes have peculiar retention onset and cut-off characteristics. Due to a modified sieving profile, MCO membranes have also been described as high-retention onset. The significant internal filtration achieved in MCO haemodialysers provides a remarkable convective clearance of medium to high MW solutes. The marginal loss of albumin observed in MCO membranes compared with high cut-off membranes is considered acceptable, if not beneficial, producing a certain clearance of protein-bound solutes. The application of MCO membranes in a classic dialysis modality characterizes a new technique called expanded haemodialysis. This therapy does not need specific software or dedicated hardware, making its application possible in every setting where the quality of dialysis fluid meets current standards.

Extracorporeal techniques for the treatment of critically ill patients with sepsis beyond conventional blood purification therapy: the promises and the pitfalls.

Sepsis is one of the leading causes of morbidity and mortality worldwide. It is characterized by a dysregulated immune response to infections that results in life-threatening organ dysfunction and even death. Bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns (PAMPs), as well as damage-associated molecular patterns (DAMPs) released by host injured cells, are well-recognized triggers resulting in the elevation of both pro-inflammatory and anti-inflammatory cytokines. Understanding this complex pathophysiology has led to the development of therapeutic strategies aimed at restoring a balanced immune response by eliminating/deactivating these inflammatory mediators. Different extracorporeal techniques have been studied in recent years in the hope of maximizing the effect of renal replacement therapy in modulating the exaggerated host inflammatory response, including the use of high volume hemofiltration (HVHF), high cut-off (HCO) membranes, adsorption alone, and coupled plasma filtration adsorption (CPFA). These strategies are not widely utilized in practice, depending on resources and local expertise. The literature examining their use in septic patients is growing, but the evidence to support their use at this stage is considered of low level. Our aim is to provide a comprehensive overview of the technical aspects, clinical applications, and associated side effects of these techniques.

Biocompatibility and Cytotoxic Evaluation of New Sorbent Cartridges for Blood Hemoperfusion.

BACKGROUND/AIMS: The use of adsorption cartridges for hemoperfusion (HP) is rapidly evolving. For these devices, the potential induced cytotoxicity is an important issue. The aim of this study was to investigate potential in vitro cytotoxic effects of different sorbent cartridges, HA130, HA230, HA330, HA380 (Jafron, China), on U937 monocytes. METHODS: Monocytes were exposed to the sorbent material in static and dynamic manners. In static test, cell medium samples were collected after 24 h of incubation in the cartridges. In dynamic test, HP modality has been carried out and samples at 30, 60, 90, and 120 min were collected. RESULTS: Compared to control samples, there was no evidence of increased necrosis or apoptosis in monocytes exposed to the cartridges both in the static and dynamic tests. CONCLUSION: Our in vitro testing suggests that HA cartridges carry an optimal level of biocompatibility and their use in HP is not associated with adverse reactions or signs of cytotoxicity.

How Does Continuous Renal Replacement Therapy Affect Septic Acute Kidney Injury?

Sepsis is the leading cause of acute kidney injury (AKI) in the intensive care unit. As the most common treatment of septic AKI, it is believed that continuous renal replacement therapy (CRRT) can not only maintain the water balance and excrete the metabolic products but also regulate the inflammation and promote kidney recovery. CRRT can remove the inflammatory cytokines to regulate the metabolic adaption in kidney and restore the kidney recovery to protect the kidney in septic AKI. Second, CRRT can provide extra energy supply in septic AKI to improve the kidney energy balance in septic AKI. Third, the anticoagulant used in CRRT also regulates the inflammation in septic AKI. CRRT is not only a treatment to deal with the water balance and metabolic products, but also a method to regulate the inflammation in septic AKI.

Quantification of Internal Filtration in Hollow Fiber Hemodialyzers with Medium Cut-Off Membrane.

BACKGROUND: Inadequate removal of molecules between 5 and 50 KDa may cause long-term complication in chronic hemodialysis. Medium cut-off (MCO) is a new class of membranes with enhanced sieving properties and negligible albumin loss. MCO membrane makes it possible to perform expanded hemodialysis (HDx), a technique based on high internal filtration (IF).The present study is designed to quantify IF in 2 MCO dialyzers (Theranova 400 and 500, Baxter, Deerfield, USA) using a nuclear imaging technique previously validated. METHODS: Blood and dialysate compartment pressure drop along with transmembrane pressure; they were measured in a closed in vitro circuit with human blood (blood flow [QB] = 300 and 400 mL/min; dialysate flow 500 mL/min; net ultrafiltration rate 0 mL/min). A non-diffusible marker molecule (albumin macro-aggregates labeled with 99Tc metastable) was injected in the blood compartment and nuclear emission was recorded by a gamma camera. Relative variations in the concentration of the marker molecule along the length of the filter were used to calculate local cross filtration. RESULTS: Based on marker concentration profiles, IF was estimated. For Theranova 400, IF were 29.7 and 41.6 mL/min for QB of 300 and 400 mL/min. For Theranova 500, IF were 31.6 and 53.1 mL/min for QB of 300 and 400 mL/min respectively. CONCLUSIONS: MCO membrane provides significant amounts of IF due to the particular combination between hydraulic permeability of the membrane and reduced inner diameter of the fibers. High IF combined with enhanced sieving profile of MCO membrane leads to improved removal of a wider spectrum of uremia retention molecules in HDx, without requiring complex equipment.

Albumin Loss and Citrate Load in Pre-Dilution High Cut-Off-CVVHDF with Regional Citrate (18 mmol/L) and High Cut-Off CVVHD with Systemic Heparin: An in vitro Study.

BACKGROUND: Convective therapies with high cut-off membranes (HCO) are usually not recommended because of theoretical excessive albumin loss. The aim of this in vitro study is to demonstrate the noninferior safety of pre-dilution hemodiafiltration with HCO (HCO-CVVHDF) with isotonic citrate anticoagulation (18 mmol/L) with respect to heparin anticoagulated hemodialysis with HCO (HCO-CVVHD) in terms of albumin removal and citrate load. METHOD: -Albumin removal was compared in vitro between 3 pre--dilution-HCO-CVVHDF with citrate anticoagulation and 3 -HCO-CVVHD with heparin anticoagulation during 30-min single-pass and 180-min recirculation phases. RESULTS: Considering concentrations and flows in the extracorporeal circuit, the transmembrane albumin removal was 2.06 (1.51; 2.09) g and 2.09 (1.9; 2.8) g respectively for HCO-CVVHDF and HCO-CVVHD, during the single-pass phase; 2.8 (2.67; 4.59) g and 2.54 (2.35; 4.67) g, respectively, for HCO-CVVHDF and HCO-CVVHD during the recirculation phase. Based on the citrate saturation coefficients, a citrate metabolic load of 8.86 mmol/h has been calculated for HCO-CVVHDF. CONCLUSION: HCO-CVVHDF performed with regional anticoagulation with 18 mmol/L citrate solution does not induce higher -albumin transmembrane removal compared to HCO-CVVHD.

The future of critical care: renal support in 2027.

Since its inception four decades ago, both the clinical and technologic aspects of continuous renal replacement therapy (CRRT) have evolved substantially. Devices now specifically designed for critically ill patients with acute kidney injury are widely available and the clinical challenges associated with treating this complex patient population continue to be addressed. However, several important questions remain unanswered, leaving doubts in the minds of many clinicians about therapy prescription/delivery and patient management. Specifically, questions surrounding therapy dosing, timing of initiation and termination, fluid management, anticoagulation, drug dosing, and data analytics may lead to inconsistent delivery of CRRT and even reluctance to prescribe it. In this review, we discuss current limitations of CRRT and potential solutions over the next decade from both a patient management and a technology perspective. We also address the issue of sustainability for CRRT and related therapies beyond 2027 and raise several points for consideration.

Nomenclature for renal replacement therapy and blood purification techniques in critically ill patients: practical applications.

This article reports the conclusions of the second part of a consensus expert conference on the nomenclature of renal replacement therapy (RRT) techniques currently utilized to manage acute kidney injury and other organ dysfunction syndromes in critically ill patients. A multidisciplinary approach was taken to achieve harmonization of definitions, components, techniques, and operations of the extracorporeal therapies. The article describes the RRT techniques in detail with the relevant technology, procedures, and phases of treatment and key aspects of volume management/fluid balance in critically ill patients. In addition, the article describes recent developments in other extracorporeal therapies, including therapeutic plasma exchange, multiple organ support therapy, liver support, lung support, and blood purification in sepsis. This is a consensus report on nomenclature harmonization in extracorporeal blood purification therapies, such as hemofiltration, plasma exchange, multiple organ support therapies, and blood purification in sepsis.

Nomenclature for renal replacement therapy in acute kidney injury: basic principles.

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

CVVHD treatment with CARPEDIEM: small solute clearance at different blood and dialysate flows with three different surface area filter configurations.

BACKGROUND: The CARdiorenal PEDIatric EMergency (CARPEDIEM) machine was originally designed to perform only continuous venovenous hemofiltration (CVVH) in neonatal and pediatric patients. In some cases, adequate convective clearance may not be reached because of a limited blood flow. In such conditions, the application of diffusive clearance [continuous venovenous hemodialysis (CVVHD)] would help optimize blood purification. In this study, the CARPEDIEM™ machine was modified to enable the circulation of dialysis through the filter allowing testing of the performance of CARPEDIEM™ machine in CVVHD. METHODS: Three different polyethersulfone hemodialyzers (surface area = 0.1 m(2), 0.2 m(2), and 0.35 m(2), respectively) were tested in vitro with a scheduled combination of plasma flow rates (Qp = 10-20-30 ml/min) and dialysis fluid flow rate (Qd = 5-10-15 ml/min). Three sessions were performed in co-current and one in counter-current configuration (as control) for each filter size. Clearance was measured from the blood and dialysate sides and results with mass balance error greater than 5 % were discarded. RESULTS: Urea and creatinine clearances for each plasma/dialysate combination are reported: clearance increase progressively for every filter proportionally to plasma flow rates. Similarly, clearances increase progressively with dialysate flow rates at a given plasma flow. The clearance curve tends to present a steep increase for small increases in plasma flow in the range below 10 ml/min, while the curve tends to plateau for values averaging 30 ml/min. As expected, the plateau is reached earlier with the smaller filter showing the effect of membrane surface-area limitation. At every plasma flow, the effect of dialysate flow increase is evident and well defined, showing that saturation of effluent was not achieved completely in any of the experimental conditions explored. No differences (p > 0.05 for all values) were obtained in experiments using whole blood instead of plasma or using co-current versus counter-current dialysate flow configuration. CONCLUSIONS: Although plasma flow and filter surface give an important contribution to the level of clearance urea and creatinine, it appears evident that dialysate flow plays an essential role in the blood purification process, justifying the use of CVVHD versus CVVH in case of high dialysis dose requirement and/or limited blood flow rate.

Con-Current versus Counter-Current Dialysate Flow during CVVHD. A Comparative Study for Creatinine and Urea Removal.

BACKGROUND: Dialysate fluid connection to the membrane in continuous dialysis may affect solute clearance. Although circuit connections are routinely made counter-current to blood flow in intermittent dialysis, no study has assessed the effect of this dialysate fluid flow direction on removal of small solutes creatinine and urea during treatment using continuous veno-venous haemodialysis (CVVHD). AIMS: To assess if dialysate flow direction during CVVHD affects small solute removal. METHODS: This ethics-approved study recruited a convenience sample of 26 adult ICU patients requiring continuous dialysis to assess urea and creatinine removal for con-current vs. counter-current dialysate flow direction. The circuit was adjusted from continuous veno-venous haemodiafiltration to CVVHD 20 min prior to sampling with no fluid removal. Blood (b) and spent dialysate fluid (f) were taken in both concurrent and counter-current fluid flow at 1 (T1) and 4 (T4) hours with a new treatment. Blood flow was 200 ml/min. Dialysate flow 33 ml/min. Removal of urea and creatinine was expressed as the diafiltrate/plasma concentration ratio: Uf/b and Cf/b respectively. Data lacking normal distribution are presented as median with 25th and 75th interquartile ranges (IQR), otherwise as mean with SD and assessed with the independent t test for paired data. p < 0.5 was considered significant. RESULTS: Fifteen male patients were included with a median (IQR) age of 67 years (52-75), and APACHE x0399;x0399; score 17 (14-19) with all patients meeting RIFLE criteria 'F'. At both times, the counter-current dialysate flow was associated with higher mean (SD) diafiltrate/plasma concentration ratios: T1 0.87 (0.16) vs. 0.77 (0.10), p = 0.006; T2 0.96 (0.16) vs. 0.76 (0.09), p < 0.001 for creatinine and T1 0.98 (0.09) vs. 0.81 (0.09), p < 0.001; T2 0.99 (0.07) vs. 0.82 (0.08), p < 0.001 for urea. CONCLUSION: Counter-current dialysate flow during CVVHD for ICU patients is associated with an approximately 20% increase in removal of small solutes creatinine and urea. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=441270.

Wearable devices for blood purification: principles, miniaturization, and technical challenges.

The prevalences of end-stage renal disease (ESRD) and renal replacement therapy (RRT) continue to increase across the world imposing staggering costs on providers. Therefore, strategies to optimize the treatment and improve survival are of fundamental importance. Despite the benefits of daily dialysis, its implementation is difficult and wearable hemodialysis might represent an alternative by which frequent treatments can be delivered to ESRD patients with much less interference in their routines promoting better quality of life. The development of the wearable artificial kidney (WAK) requires incorporation of basic components of a dialysis system into a wearable device that allows mobility, miniaturization, and above all, patient-oriented management. The technical requirements necessary for WAK can be divided into the following broad categories: dialysis membranes, dialysis regeneration, vascular access, patient monitoring systems, and power sources. Pumping systems for blood and other fluids are the most critical components of the entire device.

Wak engineering evolution.

The wearable artificial kidney (WAK) is a device that allows prolonged and frequent dialysis treatments for patients with end stage renal disease. It potentially provides a practical and feasible solution to satisfy the need for an optimal delivered dialysis. Until now, the WAK has already been presented in several models, proposing different therapeutic modalities and engineering approaches. The ideal solution of a WAK may come from a combination of all the prototypes developed and/or those currently in development. Consequently, it is important to have a complete overview and a deep knowledge of the possible engineering solutions in order to achieve the incremental steps necessary to solve the remaining issues of wearable extracorporeal blood purification devices. Since technical advances are continuously evolving and it is important to focus on clinical requirements and needs, a multidisciplinary collaboration has to be coordinated to achieve the final objective of the practical realization of a wearable artificial kidney. In such a context, the main aim of this article was to analyze more in detail the WAK Engineeristic Development.