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

Abstract

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 NCT02280005.

Funding: The Wearable Artificial Kidney Foundation and Blood Purification Technologies Inc.

Figures

Figure 1. Study enrollment.

WAK, wearable artificial kidney.

Figure 2. Mean plasma concentrations of blood urea nitrogen and β2-microglobulin during conventional hemodialysis before WAK and paired WAK treatment study periods.

Data are presented as mean ± SD for each time point. (A) Blood urea nitrogen (mg/dl). (B) Plasma β2-microglobulin (mg/l). HD, hemodialysis; WAK, wearable artificial kidney.

Figure 3. Summary of small solute and middle molecule clearance, blood flow, and dialysate flow.

(A) Plasma urea, creatinine, phosphorus, and β2-microglobulin clearance (ml/min). (B) Blood and dialysate flow (ml/min). Horizontal lines within boxes indicate median values, diamonds indicate mean values, top and bottom margins of boxes represent 25th and 75th percentile values, and whiskers indicate the range of values within 1.5 multiples of the interquartile range.

Figure 4. Mean small solute and middle molecule clearances, blood flow, and dialysate flow over the 24-hour wearable artificial kidney treatment period.

Mean plasma creatinine, urea, phosphorus, and β2-microglobulin clearance (ml/min) calculated using the blood-based Fick equation are shown as solid lines, with values corresponding to the left-sided y axis. Blood and dialysate flow (ml/min) are shown as dashed lines, with values corresponding to the right-sided y axis.

Figure 5. Time-varying small solute and middle molecule clearances, blood flow, and dialysate flow for individual subjects over the 24-hour wearable artificial kidney treatment period.

Plasma creatinine, urea, phosphorus, and β2-microglobulin clearance calculated using the blood-based Fick equation are shown as solid lines, with values corresponding to the left-sided y axis. Blood and dialysate flow are shown as dashed lines, with values corresponding to the right-sided y axis. Data are shown for the 6 individuals who completed ≥8 hours of study treatment.

Figure 6. Prototype wearable artificial kidney.

The prototype device assembled and worn and fastened in position.

Figure 7. Detailed schematic flow diagram of WAK blood and dialysate circuits.

ZP, zirconium phosphate; HZO, hydrous zirconium oxide; CO2EF, semipermeable degassing bubble removal mechanism; WAK, wearable artificial kidney.