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.

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.

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.