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Victor Gura - One of the best experts on this subject based on the ideXlab platform.
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mxene sorbents for removal of urea from dialysate a step toward the wearable Artificial Kidney
2018Co-Authors: Victor Gura, Fayan Meng, Mykola Seredych, Chi Chen, Sergey V Mikhalovsky, Susan Sandeman, Ganesh IngavleAbstract:The wearable Artificial Kidney can deliver continuous ambulatory dialysis for more than 3 million patients with end-stage renal disease. However, the efficient removal of urea is a key challenge in miniaturizing the device and making it light and small enough for practical use. Here, we show that two-dimensional titanium carbide (MXene) with the composition of Ti3C2Tx, where Tx represents surface termination groups such as −OH, −O–, and −F, can adsorb urea, reaching 99% removal efficiency from aqueous solution and 94% from dialysate at the initial urea concentration of 30 mg/dL, with the maximum urea adsorption capacity of 10.4 mg/g at room temperature. When tested at 37 °C, we achieved a 2-fold increase in urea removal efficiency from dialysate, with the maximum urea adsorption capacity of 21.7 mg/g. Ti3C2Tx showed good hemocompatibility; it did not induce cell apoptosis or reduce the metabolizing cell fraction, indicating no impact on cell viability at concentrations of up to 200 μg/mL. The biocompatibi...
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a wearable Artificial Kidney for patients with end stage renal disease
2016Co-Authors: Victor Gura, Matthew B Rivara, Scott D Bieber, Raj Munshi, Nancy Colobong Smith, Lori Linke, John Kundzins, Masoud BeizaiAbstract:BACKGROUND. Stationary hemodialysis machines hinder mobility and limit activities of daily life during dialysis treatments. New hemodialysis technologies are needed to improve patient autonomy and enhance quality of life. METHODS. We conducted a FDA-approved human trial of a wearable Artificial Kidney, a miniaturized, wearable hemodialysis machine, based on dialysate-regenerating sorbent technology. We aimed to determine the efficacy of the wearable Artificial Kidney in achieving solute, electrolyte, and volume homeostasis in up to 10 subjects over 24 hours. RESULTS. During the study, all subjects remained hemodynamically stable, and there were no serious adverse events. Serum electrolytes and hemoglobin remained stable over the treatment period for all subjects. Fluid removal was consistent with prescribed ultrafiltration rates. Mean blood flow was 42 ± 24 ml/min, and mean dialysate flow was 43 ± 20 ml/min. Mean urea, creatinine, and phosphorus clearances over 24 hours were 17 ± 10, 16 ± 8, and 15 ± 9 ml/min, respectively. Mean β2-microglobulin clearance was 5 ± 4 ml/min. Of 7 enrolled subjects, 5 completed the planned 24 hours of study treatment. The trial was stopped after the seventh subject due to device-related technical problems, including excessive carbon dioxide bubbles in the dialysate circuit and variable blood and dialysate flows. CONCLUSION. Treatment with the wearable Artificial Kidney was well tolerated and resulted in effective uremic solute clearance and maintenance of electrolyte and fluid homeostasis. These results serve as proof of concept that, after redesign to overcome observed technical problems, a wearable Artificial Kidney can be developed as a viable novel alternative dialysis technology. TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02280005","term_id":"NCT02280005"}}NCT02280005. FUNDING. The Wearable Artificial Kidney Foundation and Blood Purification Technologies Inc.
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the future of the Artificial Kidney moving towards wearable and miniaturized devices
2011Co-Authors: C Ronco, Andrew Davenport, Victor GuraAbstract:New directions in dialysis research include cheaper treatments, home based therapies and simpler methods of blood purification. These objectives may be probably obtained with innovations in the field of Artificial Kidney through the utilization of new disciplines such as miniaturization, microfluidics, nanotechnology. This research may lead to a new era of dialysis in which the new challenges are transportability, wearability and why not the possibility to develop implantable devices. Although we are not there yet, a new series of papers have recently been published disclosing interesting and promising results on the application of wearable ultrafiltration systems (WUF) and wearable Artificial Kidneys (WAK). Some of them use extracorporeal blood cleansing as a method of blood purification while others use peritoneal dialysis as a treatment modality (ViWAK and AWAK.) A special mention deserves the wearable/portable ultrafiltration system for the therapy of overhydration and congestive heart failure (WAKMAN). This system will allow dehospitalization and treatment of patients with less comorbidity and improved tolerance. On the way to the wearable Artificial Kidney, new discoveries have been made such as a complete system for hemofiltration in newborns (CARPEDIEM). The neonate in fact is the typical patient who may benefit from miniaturization of the dialysis circuit. This review analyzes the rationale for such endeavour and the challenges to overcome in order to make possible a true ambulatory dialysis treatment. Some initial results with these new devices are presented. We would like to stimulate a collaborative effort to make a quantum leap in technology making the wearable Artificial Kidney a reality rather than a dream.
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from wearable ultrafiltration device to wearable Artificial Kidney
2011Co-Authors: Andrew Davenport, Claudio Ronco, Victor GuraAbstract:Introduction : Since the inception of hemodialysis as a treatment for patients with chronic Kidney disease, there have been designs created for portable, wearable or implantable devi
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technical breakthroughs in the wearable Artificial Kidney wak
2009Co-Authors: Victor Gura, Masoud Beizai, Carlos Ezon, Alexandra S Macy, Thomas A GolperAbstract:Background: The wearable Artificial Kidney (WAK) has been a holy grail in Kidney failure for decades. Described herein are the breakthroughs that made possible the creation of the WAK V1.0 and its advanced versions V 1.1 and 1.2. Design: The battery-powered WAK pump has a double channel pulsatile counter phase flow. This study clarifies the role of pulsatile blood and dialysate flow, a high-flux membrane with a larger surface area, and the optimization of the dialysate pH. Flows and clearances from the WAK pump were compared with conventional pumps and with gravity steady flow. Results: Raising dialysate pH to 7.4 increased adsorption of ammonia. Clearances were higher with pulsatile flow as compared with steady flow. The light WAK pump, geometrically suitable for wearability, delivered the same clearances as larger and heavier pumps that cannot be battery operated. Beta2 microglobulin (2M) was removed from human blood in vitro. Activated charcoal adsorbed most 2M in the dialysate. The WAK V1.0 delivered an effective creatinine clearance of 18.5 3.2 ml/min and the WAK V1.1 27.0 4.0 ml/min in uremic pigs. Conclusions: Half-cycle differences between blood and dialysate, alternating transmembrane pressures (TMP), higher amplitude pulsations, and a push-pull flow increased convective transport. This creates a yet undescribed type of hemodiafiltration. Further improvements were achieved with a larger surface area high-flux dialyzer and a higher dialysate pH. The data suggest that the WAK might be an efficient way of providing daily dialysis and optimizing end stage renal disease (ESRD) treatment. Clin J Am Soc Nephrol 4: 1441–1448, 2009. doi: 10.2215/CJN.02790409
Claudio Ronco - One of the best experts on this subject based on the ideXlab platform.
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wearable Artificial Kidney and wearable ultrafiltration device vascular access future directions
2019Co-Authors: Ana Castro, Mauro Neri, Akash Nayak Karopadi, Anna Lorenzin, Nicola Marchionna, Claudio RoncoAbstract: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.
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personal daily dialysis the evolution of the Artificial Kidney
2013Co-Authors: Jeong Chul Kim, Claudio RoncoAbstract:To improve hemodialysis (HD) patients' clinical tolerance and quality of life, a new paradigm of technological evolution of the Artificial Kidney needs to be addressed at this point. Compared to the second law of thermodynamics, if HD is a barrier against entropy increase, personal daily dialysis (PDD), taking account of multidimensional treatment parameters specific to the patient, can be a new treatment option. Here, we review currently used HD equipment and competing technologies of the wearable Artificial Kidney (WAK) for future application to PDD. Biofeedback control during HD personalizes treatment parameters such as blood volume changes, thermal energy balance and biochemical variables in well-defined ranges and tries to deliver the targeted treatment dose without intradialytic hypotension. Miniaturized devices such as WAK could also meet the needs of patients by providing mobility, the possibility of normal social activities and flexibility of treatment schedule. So far, many studies have shown the future direction of renal replacement therapy for chronic patients: personalization and daily treatment. PDD might require a new index including a biological plan for recovery of homeostasis and a strategy toward long-term rehabilitation of the patient. The concept of entropy includes these multidimensional factors, and the Artificial Kidney should be evolved to minimize the increase in entropy of the patient.
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a wearable Artificial Kidney technical requirements and potential solutions
2011Co-Authors: Jeong Chul Kim, Francesco Garzotto, Federico Nalesso, Dinna N Cruz, Ji Hyun Kim, Eungtaek Kang, Hee Chan Kim, Claudio RoncoAbstract:Recently, new approaches for miniaturization and transportability of medical devices have been developed, paving the way for wearability and the possibility of implantation, for renal replacement therapies. A wearable Artificial Kidney (WAK) is a medical device that supports renal function during ambulation or social activities out of hospital. With the aim of improving dialysis patients’ quality of life, WAK systems have been developed for several decades. However, at present there are a lot of technical issues confronting the attempt to apply WAK systems in clinical practice. This article focuses on technical requirements and potential solutions for WAKs and reviews up-to-date approaches related to dialysis membrane, dialysate regeneration, vascular access, patient-monitoring systems and power sources for WAKs.
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current technological approaches for a wearable Artificial Kidney
2011Co-Authors: Jeong Chul Kim, Claudio RoncoAbstract:A wearable Artificial Kidney (WAK) is a device that continuously supports renal function during ambulation or social activities out of hospital. With the aim of improving dialysis patients' quality of life, WAK systems have been in development for several decades. Technological evolutions in dialysis membrane and dialysate regeneration have been paving the way to wearability, and the possibility of implantation, for renal replacement therapies. However, at present, there are many technical issues confronting the attempts to apply WAK systems in clinical practice. Here, we have reviewed the necessary technical requirements and the WAKs currently being developed that are trying to meet these. Aside from technical issues, ethical, legal and economic aspects should be also considered together, in order to minimize trial and error in the development of the WAK. Continuous follow- up, integration with emerging new technologies, and multidisciplinary approaches involving clinicians, engineers, economists and social scientists are required for the realization of WAK in clinical practice.
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from wearable ultrafiltration device to wearable Artificial Kidney
2011Co-Authors: Andrew Davenport, Claudio Ronco, Victor GuraAbstract:Introduction : Since the inception of hemodialysis as a treatment for patients with chronic Kidney disease, there have been designs created for portable, wearable or implantable devi
William H Fissell - One of the best experts on this subject based on the ideXlab platform.
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a scalable hierarchical rib design for larger area higher porosity nanoporous membranes for the implantable bio Artificial Kidney
2020Co-Authors: Benjamin W Chui, William H Fissell, Nathan Wright, David A Maginnis, Tariq M Haniff, Charles Blaha, Shuvo RoyAbstract:Silicon nanoporous membranes provide the fundamental underlying technology for the development of an implantable bio-Artificial Kidney. These membranes, which are comprised of micromachined slit-pores that are nominally 10 nm wide, allow for high-efficiency blood filtration as well as immunoprotection for encapsulated cells. Our approach takes advantage of well-established semiconductor fabrication technology to give us precise dimensional control over pore widths, thereby enabling a highly selective filtration function and a clear path towards further miniaturization. This work builds on our prior results on “ribbed nanoporous membranes” by adding a second-level hierarchy of significantly taller “mega-ribs” to further strengthen the membranes. Relying on a two-step Deep Reactive Ion Etch (DRIE) process, we etch $4~\mu \text{m}$ -deep as well as $40~\mu \text{m}$ -deep trenches into a silicon substrate, grow a thermal oxide liner, and deposit a layer of polysilicon into this “mold” to form membranes which, when released after a backside DRIE etch, feature a network of reinforcing ribs on the underside. We have fabricated and tested freestanding membrane spans that are up to 14 times wider than before, with approximately double the measured permeability per unit area. The new architecture can also improve cross-membrane mass-transfer rates and reduce chip-fabrication costs. [2020-0170]
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genome engineering renal epithelial cells for enhanced volume transport function
2020Co-Authors: Matthew H Wilson, Ruth Ann Veach, Wentian Luo, R Welch, Shuvo Roy, William H FissellAbstract:Introduction Bioengineering an implantable Artificial Kidney (IAK) will require renal epithelial cells capable of reabsorption of salt and water. We used genome engineering to modify cells for improved Na+/H+ exchange and H2O reabsorption. The non-viral piggyBac transposon system enables genome engineering cells to stably overexpress one or more transgenes simultaneously. Methods We generated epitope-tagged human sodium hydrogen exchanger 3 (NHE3) and aquaporin-1 (AQP1) cDNA expressing piggyBac transposon vectors. Transgene expression was evaluated via western blot and immunofluorescence. Flow cytometry analysis was used to quantitate transporter expression in a library of genome engineered clones. Cell surface biotinylation was used evaluate surface protein localization. Blister formation assays were used to monitor cellular volumetric transport. Results piggyBac enabled stable transposon integration and overexpression of cumate-inducible NHE3 and/or constitutively expressing AQP1 in cultured renal (MDCK) epithelial cells. Cell surface delivery of NHE3 and AQP1 was confirmed using cell surface biotinylation assays. Flow cytometry of a library of MDCK clones revealed varying expression of AQP1 and NHE3. MDCK cells expressing AQP1 and cumate-inducible NHE3 demonstrated increased volumetric transport. Conclusions Our results demonstrate that renal epithelial cells an be genome engineered for enhanced volumetric transport that will be needed for an IAK device. Our results lay the foundation for future studies of genome engineering human Kidney cells for renal tubule cell therapy.
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original article submission platelet stress accumulation analysis to predict thrombogenicity of an Artificial Kidney
2018Co-Authors: Amanda K W Buck, Steven G Goebel, Mark S Goodin, Nathan Wright, Joseph J Groszek, Jarrett Moyer, Sukhveer Singh, Danny Bluestein, William H FissellAbstract:Abstract An implantable Artificial Kidney using a hemofilter constructed from an array of silicon membranes to provide ultrafiltration requires a suitable blood flow path to ensure stable operation in vivo . Two types of flow paths distributing blood to the array of membranes were evaluated: parallel and serpentine. Computational fluid dynamics (CFD) simulations were used to guide the development of the blood flow paths. Pressure data from animal tests were used to obtain pulsatile flow conditions imposed in the transient simulations. A key consideration for stable operation in vivo is limiting platelet stress accumulation to avoid platelet activation and thrombus formation. Platelet stress exposure was evaluated by CFD particle tracking methods through the devices to provide distributions of platelet stress accumulation. The distributions of stress accumulation over the duration of a platelet lifetime for each device revealed that stress accumulation for the serpentine flow path exceeded levels expected to cause platelet activation while the accumulated stress for the parallel flow path was below expected activation levels.
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achieving more frequent and longer dialysis for the majority wearable dialysis and implantable Artificial Kidney devices
2013Co-Authors: William H Fissell, Shuvo Roy, Andrew DavenportAbstract:The long-term survival for many chronic Kidney failure patients who remain treated by dialysis in economically advanced countries remains similar to that of those with solid-organ malignancy, despite a disproportionate amount of health-care expenditure. As such, the current paradigm of three times weekly in-center hemodialysis for 4h or shorter sessions needs to change to improve patient outcomes. Although more frequent and longer dialysis sessions have been reported to improve cardiovascular risk surrogates and short-term outcomes, these options are only practically available to a very small fraction of the total dialysis population. As such, radically new approaches are required to improve patient outcomes and quality of life for the majority of dialysis patients. Currently, two different approaches are being developed, wearable devices based on current dialysis techniques and more futuristic implantable devices modeled on the natural nephron.
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the implantable Artificial Kidney
2009Co-Authors: William H Fissell, Shuvo RoyAbstract:The confluence of an increasing prevalence of end-stage renal disease (ESRD), clinical trial data suggestive of benefit from quotidian dialysis, and ongoing cost/benefit reanalysis of healthcare spending have stimulated interest in technological improvements in provision of ESRD care. For the last decade, our group has focused on enabling technologies that would permit a paradigm shift in dialysis care similar to that brought by implantable defibrillators to arrhythmia management. Two significant barriers to wearable or implantable dialysis persist: package size of the dialyzer and water requirements for preparation of dialysate. Decades of independent research into highly efficient membranes and cell-based bioreactors culminated in a team effort to develop an implantable version of the University of Michigan Renal Assist Device. In this review, the rationale for the design of the implantable Artificial Kidney is described.
Andrew Davenport - One of the best experts on this subject based on the ideXlab platform.
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achieving more frequent and longer dialysis for the majority wearable dialysis and implantable Artificial Kidney devices
2013Co-Authors: William H Fissell, Shuvo Roy, Andrew DavenportAbstract:The long-term survival for many chronic Kidney failure patients who remain treated by dialysis in economically advanced countries remains similar to that of those with solid-organ malignancy, despite a disproportionate amount of health-care expenditure. As such, the current paradigm of three times weekly in-center hemodialysis for 4h or shorter sessions needs to change to improve patient outcomes. Although more frequent and longer dialysis sessions have been reported to improve cardiovascular risk surrogates and short-term outcomes, these options are only practically available to a very small fraction of the total dialysis population. As such, radically new approaches are required to improve patient outcomes and quality of life for the majority of dialysis patients. Currently, two different approaches are being developed, wearable devices based on current dialysis techniques and more futuristic implantable devices modeled on the natural nephron.
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the future of the Artificial Kidney moving towards wearable and miniaturized devices
2011Co-Authors: C Ronco, Andrew Davenport, Victor GuraAbstract:New directions in dialysis research include cheaper treatments, home based therapies and simpler methods of blood purification. These objectives may be probably obtained with innovations in the field of Artificial Kidney through the utilization of new disciplines such as miniaturization, microfluidics, nanotechnology. This research may lead to a new era of dialysis in which the new challenges are transportability, wearability and why not the possibility to develop implantable devices. Although we are not there yet, a new series of papers have recently been published disclosing interesting and promising results on the application of wearable ultrafiltration systems (WUF) and wearable Artificial Kidneys (WAK). Some of them use extracorporeal blood cleansing as a method of blood purification while others use peritoneal dialysis as a treatment modality (ViWAK and AWAK.) A special mention deserves the wearable/portable ultrafiltration system for the therapy of overhydration and congestive heart failure (WAKMAN). This system will allow dehospitalization and treatment of patients with less comorbidity and improved tolerance. On the way to the wearable Artificial Kidney, new discoveries have been made such as a complete system for hemofiltration in newborns (CARPEDIEM). The neonate in fact is the typical patient who may benefit from miniaturization of the dialysis circuit. This review analyzes the rationale for such endeavour and the challenges to overcome in order to make possible a true ambulatory dialysis treatment. Some initial results with these new devices are presented. We would like to stimulate a collaborative effort to make a quantum leap in technology making the wearable Artificial Kidney a reality rather than a dream.
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from wearable ultrafiltration device to wearable Artificial Kidney
2011Co-Authors: Andrew Davenport, Claudio Ronco, Victor GuraAbstract:Introduction : Since the inception of hemodialysis as a treatment for patients with chronic Kidney disease, there have been designs created for portable, wearable or implantable devi
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β2 microglobulin and phosphate clearances using a wearable Artificial Kidney a pilot study
2009Co-Authors: Victor Gura, Andrew Davenport, Masoud Beizai, Carlos Ezon, Claudio RoncoAbstract:Background Additional small-solute clearances during standard thrice-weekly hemodialysis treatments have not improved patient survival. However, these treatments have limited middle-molecule clearances. Thus, newer therapies designed to increase middle-molecule clearances need to be developed and evaluated. Study Design Pilot clinical trial to measure β 2 -microglobulin and phosphate clearances with a wearable hemodialysis device. Setting & Participants 8 regular hemodialysis patients under the care of a university teaching hospital. Intervention Patients were fitted with a wearable hemodialysis device for 4 to 8 hours. Outcomes All patients tolerated the treatment. Results Average amount of β 2 -microglobulin removed was 99.8 ± 63.1 mg, with mean clearance of 11.3 ± 2.3 mL/min, and an average of 445.2 ± 326 mg of phosphate was removed, with mean plasma phosphate clearance of 21.7 ± 4.5 mL/min. These clearances compared favorably with mean urea and creatinine plasma clearances (21.8 ± 1.6 and 20.0 ± 0.8 mL/min, respectively). Limitations Proof-of-concept preliminary trial. Additional studies are warranted to confirm these positive preliminary data. Conclusions This wearable Artificial Kidney potentially provides effective β 2 -microglobulin and phosphate clearances and, by analogy, middle-molecule clearances.
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the wearable Artificial Kidney why and how from holy grail to reality
2009Co-Authors: Victor Gura, Claudio Ronco, Andrew DavenportAbstract:Once hemodialysis had become established as a treatment for chronic Kidney disease, the early pioneers realized the limitations of the treatment, particularly in terms of the impact intermittent thrice weekly hemodialysis had on a patient's quality of life-not only time spent on dialysis and time traveling to and from treatment, but also dietary and fluid restrictions. This led to the search for the holy grail--a wearable hemodialysis device (WAK), that would allow patients to receive continuous treatment, while going on with the normal activities of daily life. Such a device would not only provide adequate solute clearances and control both electrolyte and acid-base status, but also improve blood pressure control--all while allowing a liberal diet. Despite many attempts, to develop such a wearable Artificial Kidney, it is only recently, with the advent of microtechnologies, that it has been possible to construct a truly wearable device, which can accurately regulate ultrafiltration and achieve adequate solute clearances. One such device has recently completed successful human pilot studies, designed to test device reliability, safety, and efficacy.
Ganesh Ingavle - One of the best experts on this subject based on the ideXlab platform.
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mxene sorbents for removal of urea from dialysate a step toward the wearable Artificial Kidney
2018Co-Authors: Victor Gura, Fayan Meng, Mykola Seredych, Chi Chen, Sergey V Mikhalovsky, Susan Sandeman, Ganesh IngavleAbstract:The wearable Artificial Kidney can deliver continuous ambulatory dialysis for more than 3 million patients with end-stage renal disease. However, the efficient removal of urea is a key challenge in miniaturizing the device and making it light and small enough for practical use. Here, we show that two-dimensional titanium carbide (MXene) with the composition of Ti3C2Tx, where Tx represents surface termination groups such as −OH, −O–, and −F, can adsorb urea, reaching 99% removal efficiency from aqueous solution and 94% from dialysate at the initial urea concentration of 30 mg/dL, with the maximum urea adsorption capacity of 10.4 mg/g at room temperature. When tested at 37 °C, we achieved a 2-fold increase in urea removal efficiency from dialysate, with the maximum urea adsorption capacity of 21.7 mg/g. Ti3C2Tx showed good hemocompatibility; it did not induce cell apoptosis or reduce the metabolizing cell fraction, indicating no impact on cell viability at concentrations of up to 200 μg/mL. The biocompatibi...
