The relationship between intra-parenchymal renal resistive index variation and renal functional reserve in healthy subjects.

BACKGROUND: Renal functional reserve can be used as a clinical tool for risk stratification of patients undergoing potentially nephrotoxic procedures. Ultrasound assessment of intra-parenchymal renal resistive index variation-IRRIV test-has been recently proposed as a safe, reproducible, inexpensive and easy to perform technique to identify the presence of renal functional reserve. The present study has been designed to externally validate the IRRIV test in a validation cohort of healthy subjects. METHODS: We examined data from a group of 47 healthy subjects undergoing protein loading and IRRIV testing. The correlation between IRRIV and renal functional reserve was tested using Pearson correlation analysis. Concordance between presence of renal functional reserve (i.e. a value of renal functional reserve ≥ 15 ml/min/1.73 m2) and IRRIV was evaluated using logistic regression analysis. RESULTS: We found a significant correlation between IRRIV and renal functional reserve (Pearson correlation coefficient = 0.83 [95% confidence interval (CI) 0.71-0.90; p < 0.01]). Concordance between the presence of renal functional reserve and the IRRIV test was described in 45 (95.7%) subjects. In particular, a negative IRRIV test correctly predicted the absence of renal functional reserve in 5 subjects, while a positive IRRIV test correctly predicted the presence of renal functional reserve in 40 subjects. Only two subjects were incorrectly classified by the IRRIV test. IRRIV predicts renal functional reserve with a ROC-AUC of 0.86 [CI 95% 0.68-1]. CONCLUSIONS: The IRRIV test is an ultrasound technique that significantly predicts the presence and the degree of renal functional reserve in healthy subjects.

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.

How can we advance in renal replacement therapy techniques? / ¿Cómo podemos progresar en las técnicas de sustitución de la función renal?

End-Stage Renal Disease (ESRD) is one of the major causes of morbidity and mortality worldwide. Although the incidence of ESRD is relatively stable, the prevalence of maintenance dialysis is increasing, and it is expected to reach a staggering 5439 million patients worldwide by 2030. Despite the great technological evolution that has taken place in recent years, most patients are still treated with in-centre haemodialysis and their prognosis remains far from desirable. Since 1980, there has been an increasing interest in the development of a portable device for renal replacement therapy (RRT), which ultimately led to the creation of the Wearable Artificial Kidney (WAK) and the Wearable Ultrafiltration (WUF) system. Portable RRT devices may be acceptable alternatives that deal with several unmet clinical needs of ESRD patients. So far, 3 important human studies with WAK and WUF have been carried out and, although these devices require considerable technological improvement, their safety and efficacy in solute clearance and fluid removal is undeniable. In this article, we review the evolution of the WAK and the WUF and the main clinical trials performed, highlighting some of their technical features. Some of the main possible clinical advantages that could be achieved with these devices, as well as some economic aspects, are also pointed out. In the future, all renal replacement therapy techniques should evolve to perfectly match the clinical and personal needs of each patient, allowing for an improved health-related quality of life

La enfermedad renal crónica terminal (ERCT) es una de las principales causas de morbimortalidad mundial. Aunque la incidencia de esta enfermedad es relativamente estable, la prevalencia en diálisis está aumentando, y se espera que llegue a la cifra de 5.439 millones de pacientes en todo el mundo en el año 2030. A pesar de la gran evolución tecnológica ocurrida en los últimos años, la mayoría de los pacientes continúan siendo tratados con hemodiálisis, y su pronóstico queda lejos de lo deseable. Desde 1980, existe un interés creciente en el desarrollo de dispositivos portátiles para la terapia de sustitución de la función renal (TSFR), y que llevaron a la creación del Wearable Artificial Kidney (WAK) y del Wearable Ultrafiltration (WUF) system. Estos pueden ser alternativas aceptables que permiten alcanzar las necesidades de los pacientes con ERCT, que hasta ahora no se han alcanzado. A pesar de que estos dispositivos necesitan mejoras tecnológicas, su seguridad y eficacia en el aclaramiento de solutos y la eliminación de fluidos es innegable. Revisamos la evolución del WAK y del WUF, y los principales ensayos clínicos desarrollados, destacando algunas de sus particularidades tecnológicas. Adicionalmente, señalamos algunas de las posibles ventajas clínicas que podrían ser alcanzadas con estos dispositivos, así como algunos aspectos económicos. En el futuro, todas las TSFR deben evolucionar para satisfacer todas las necesidades clínicas y personales de cada paciente, permitiendo una mejor calidad de vida relacionada con la salud

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.

Wearable artificial kidney and wearable ultrafiltration device vascular access-future directions.

BACKGROUND: Since 2005, three human clinical trials have been performed with the Wearable Artificial Kidney (WAK) and Wearable Ultrafiltration (WUF) device. The lack of an adequate vascular access (VA) has been pointed out as the main limitation to their implementation. Based on the current level of understanding, we will make the first conceptual proposal of an adequate VA suitable for the WAK and the WUF. METHODS: All the literature related to WAK and WUF was reviewed. Based on eight main publications the VA major characteristics were defined: a mean blood flow of 100 mL/min; the capability to allow prolonged and frequent dialysis treatments, without interfering in activities of daily living (ADL); safe and convenient connection/disconnection systems; reduced risk of biofilm formation and coagulation; high biocompatibility. A research was done in order to answer to each necessary technological prerequisites. RESULTS: The use of a device similar to a CVC with a 5Fr lumen, seems to be the most feasible option. Totally subcutaneous port devices, like the LifeSite(R) or Dialock (R) systems can be a solution to allow WAK or WUF to operate continuously while patients carry out their ADL. Recently, macromolecules that reduce the risk of thrombosis and infection and are integrated into a CVC have been developed and have the capability of overcoming these major limitations. CONCLUSION: With an adequate VA, portable HD devices can be acceptable options to address several unmet clinical needs of HD patients.

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.

How can we advance in renal replacement therapy techniques?

End-Stage Renal Disease (ESRD) is one of the major causes of morbidity and mortality worldwide. Although the incidence of ESRD is relatively stable, the prevalence of maintenance dialysis is increasing, and it is expected to reach a staggering 5439 million patients worldwide by 2030. Despite the great technological evolution that has taken place in recent years, most patients are still treated with in-centre haemodialysis and their prognosis remains far from desirable. Since 1980, there has been an increasing interest in the development of a portable device for renal replacement therapy (RRT), which ultimately led to the creation of the Wearable Artificial Kidney (WAK) and the Wearable Ultrafiltration (WUF) system. Portable RRT devices may be acceptable alternatives that deal with several unmet clinical needs of ESRD patients. So far, 3 important human studies with WAK and WUF have been carried out and, although these devices require considerable technological improvement, their safety and efficacy in solute clearance and fluid removal is undeniable. In this article, we review the evolution of the WAK and the WUF and the main clinical trials performed, highlighting some of their technical features. Some of the main possible clinical advantages that could be achieved with these devices, as well as some economic aspects, are also pointed out. In the future, all renal replacement therapy techniques should evolve to perfectly match the clinical and personal needs of each patient, allowing for an improved health-related quality of life.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Prescription and Delivery of the Right Continuous Renal Replacement Therapies Dose.

This chapter focuses on the definitions and impact of prescription and delivery of the right dose of treatment in patients on continuous renal replacement therapy (CRRT). We define "dose" and the concepts of efficiency, intensity, and efficacy; differentiate their multiple components; and describe the practical application of those concepts to direct patient care. In the article, we emphasize the effects of delivered dose variation on solute control, and list the main factors affecting CRRT dose delivery. Finally, we summarize the main indicators of dose monitoring and emphasize the importance of an excellent quality control system to ensure appropriate delivery of care to critically ill patients with acute kidney injury.

Advances in Machine Technology.

Continuous renal replacement therapy (CRRT) machines have evolved into devices specifically designed for critically ill over the past 40 years. In this chapter, a brief history of this evolution is first provided, with emphasis on the manner in which changes have been made to address the specific needs of the critically ill patient with acute kidney injury. Subsequently, specific examples of technology developments for CRRT machines are discussed, including the user interface, pumps, pressure monitoring, safety features, and anticoagulation capabilities.

Discontinuation of Continuous Renal Replacement Therapy and Dialysis Dependence.

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.