MXene Sorbents for Removal of Urea from Dialysate: A Step toward the Wearable Artificial Kidney.

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 Ti3C2T x, where T x 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. Ti3C2T x 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 biocompatibility of Ti3C2T x and its selectivity for urea adsorption from dialysate open a new opportunity in designing a miniaturized dialysate regeneration system for a wearable artificial kidney.

A wearable artificial kidney for patients with end-stage renal disease.

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 ß2-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 NCT02280005. FUNDING: The Wearable Artificial Kidney Foundation and Blood Purification Technologies Inc.

From wearable ultrafiltration device to wearable artificial kidney.

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 devices to improve both quality of therapy delivered and patient quality of life. METHODS: We conducted a pilot proof- of- concept study in 8 stable adult hemodialysis patients using a wearable hemodialysis device with a sorbent-based regeneration dialysate system. RESULTS: All patients were safely treated for 4-8 h. Ultrafiltration was successfully performed without any cardiovascular effects, with a reduction in extracellular fluid to total body fluid ratio (from 0.339 ± 0.003 to 0.335 ± 0.003 after treatment; p=0.002). Respective clearances (ml/min) were: 22.6 ± 1.8 for urea, 20.7 ± 1.8 for creatinine, 21.7 ± 1.8 for phosphate and 11.6 ± 1.8 for ß(2)-microglobulin. Although the small solute clearances are much lower than for conventional intermittent hemodialysis, this device has been designed to operate for sustained periods, and therefore would be predicted to have equivalent small solute clearances to continuous dialysis treatments (CRRT) in the intensive setting. Safety mechanisms were shown to operate promptly in a case of a venous needle disconnection, and in cases of circuit clotting. CONCLUSION: This was a pilot study designed to demonstrate the safety of a wearable hemodialysis device. In addition to confirming safety, we were able to confirm that the device not only had similar clearances to CRRT used in the intensive-care setting, but also increased clearances of middle molecules, such as ß(2)-microglobulin and phosphate.

Portable and wearable dialysis: where are we now?

Although dialysis is a life-saving treatment for patients with acute and chronic kidney disease, mortality remains high, with the survival of patients treated by regular hemodialysis similar to that of some solid organ tumors. Recent reports have suggested that a major increase in the dose of dialysis, delivered by frequent nocturnal dialysis, may improve survival. Unfortunately, only a minority of centers can offer this type of therapy, and only to a minority of their patients. Thus, to improve access to dialysis as well as increase the delivered dose of dialysis, a major change in the current paradigm of dialysis delivery is required. For many years, the "holy grail" of dialysis has been to develop a wearable or portable system, allowing patients to be treated while performing their normal activities of daily living. It is only recently with the advances in technology that such dialysis devices have been possible. Prototype devices for both hemodialysis and peritoneal dialysis have been studied with favorable results. Typically, these have been short-term studies, and longer term trials are eagerly awaited, to determine whether the current generation of wearable continuous dialysis devices cannot only remove waste products of metabolism and control volume but also maintain acid-base and electrolyte homeostasis and actually improve outcomes. In addition, a novel generation of dialysis devices based on nanotechnologies are being developed. Hopefully, these wearable continuous devices will be available as an option for routine clinical practice in the not-too-distant future.

Technical breakthroughs in the wearable artificial kidney (WAK).

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. Beta(2) microglobulin (beta(2)M) was removed from human blood in vitro. Activated charcoal adsorbed most beta(2)M 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.

Beta2-microglobulin and phosphate clearances using a wearable artificial kidney: a pilot study.

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 beta(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 beta(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 beta(2)-microglobulin and phosphate clearances and, by analogy, middle-molecule clearances.

The wearable artificial kidney, why and how: from holy grail to reality.

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.

Ultrafiltration for the management of acute decompensated heart failure.

Heart failure is a major public health problem and is increasing in incidence throughout the industrialized world. Despite recent advances in pharmacotherapy, the overall mortality remains high and largely unchanged. Ultrafiltration has received increased attention in the treatment of acute decompensated congestive heart failure, and recent clinical trials suggest its usefulness in removing volume while preserving renal function. This review will focus on the background of ultrafiltration in the treatment of acute decompensated heart failure as well as the current evidence regarding its efficacy and safety.

A wearable artificial kidney: dream or reality?

The development of a wearable device that can replace conventional dialysis in patients needing chronic renal replacement therapy is not as far-fetched as it once was. Ronco et al. describe technological achievements, propose future research directions and discuss the clinical, technical and socioeconomic reasons for continuing the push to realize the wearable artificial kidney.

Toward the wearable artificial kidney.

The evolution of technology in hemodialysis has gone through several steps including the feasibility phase, the search for reliability, the implementation of automation to improve efficiency and the quest towards increased tolerance and treatment adequacy. Today, a new challenge is appearing on the scene and it concerns miniaturization, transportability, wearability and the possibility of developing implantable devices for renal replacement therapies. 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 these use extracorporeal blood cleansing as a method of blood purification while others use peritoneal dialysis as a treatment modality. This manuscript presents the initial results with these new devices and proposes an effort to make a quantum leap in technology making the wearable artificial kidney a reality rather than a dream.

A wearable haemodialysis device for patients with end-stage renal failure: a pilot study.

BACKGROUND: More frequent haemodialysis can improve both survival and quality of life of patients with chronic kidney disease. However, there is little capacity in the UK to allow patients to have more frequent haemodialysis treatments in hospital and satellite haemodialysis units. New means of delivering haemodialysis are therefore required. Our aim was to assess the safety and efficiency of a wearable haemodialysis device. METHODS: Eight patients with end-stage kidney failure (five men, three women, mean age 51.7 [SD 13.8] years) who were established on regular haemodialysis were fitted with a wearable haemodialysis device for 4-8 h. Patients were given unfractionated heparin for anticoagulation, as they would be for standard haemodialysis. FINDINGS: There were no important cardiovascular changes and no adverse changes in serum electrolytes or acid-base balance. There was no evidence of clinically significant haemolysis in any patient. Mean blood flow was 58.6 (SD 11.7) mL/min, with a dialysate flow of 47.1 (7.8) mL/min. The mean plasma urea clearance rate was 22.7 (5.2) mL/min and the mean plasma creatinine clearance rate was 20.7 (4.8) mL/min. Clotting of the vascular access occurred in two patients when the dose of heparin was decreased and the partial thromboplastin time returned towards the normal reference range in both of these patients. The fistula needle became dislodged in one patient, but safety mechanisms prevented blood loss, the needle was replaced, and treatment continued. INTERPRETATION: This wearable haemodialysis device shows promising safety and efficacy results, although further studies will be necessary to confirm these results.

Continuous renal replacement therapy for congestive heart failure: the wearable continuous ultrafiltration system.

Ultrafiltration is effective in the treatment of fluid and sodium overload in congestive heart failure. There is no available device to provide this therapy to ambulatory patients. We built and tested in vivo a wearable belt that can provide continuous ultrafiltration, 168 hours a week. Nine pigs underwent ureteral ligation and subsequently were allowed fluids ad lib, producing fluid overload. Next day, ultrafiltration was performed for 8 hours. The device consists of a hollow-fiber filter, a 9 V battery-operated pulsatile blood pump, a micro pump for heparin infusion, and another micro pump to control ultrafiltration rate. Blood flow was 65 ml/min and the weight of the device is less than 2.5 lb. Fluid removal rate ranged from 0 to 700 ml/h and averaged 106 ml/h. Salt removed was 7.6 g. No complications were observed. The potential impact on the quality of life of these patients by reducing the shortness of breath, leg swelling, and returning their ability to enjoy salt in their food might be significant, and a reduction in morbidity could be expected. The economic impact in reducing hospital admissions and length of stay, intensive care unit utilization, and drug consumption could be significant. Further studies are needed to compare this innovative approach with traditional drug-based therapy.

Continuous renal replacement therapy for end-stage renal disease. The wearable artificial kidney (WAK).

Daily dialysis offers many benefits but is difficult to implement. CRRT allows dialysis 24/7 but is not suitable for ESRD patients. Thus, the need for a miniaturized ambulatory CRRT device those patients can wear permanently. We report the feasibility, safety and efficiency in uremic pigs, of such a wearable artificial kidney (WAK) that can be worn as a belt, operated with batteries, and weights less than 5 lbs. We used a hollow fiber dialyzer with a surface area of 0.2 sqm. Dialysate was continuously regenerated by a series of cartridges containing several sorbents allowing the use of approximately 375 ml of dialysate. The device includes reservoirs with heparin and electrolytes. Average fluid removal was 100 ml/hr. The Creatinine was 25 ml/min. In 8 hrs the total Creatinine removed was 1 gr, Urea 12 gr, P0.8 gr and K 72 mEq. Weekly st kt/v was extrapolated to approximately 7. There were no side effects. The WAK can be operated safely and continuously 168 hr/week. This would allow for all the advantages of daily dialysis and reduce morbidity and mortality in the ESRD population. It will also reduce cost and manpower utilization.