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Removal of urea by electro-oxidation in a miniature dialysis device: a study in awake goats.
American Journal of Physiology. Renal Physiology 2018 July 12
BACKGROUND: The key to success in developing a wearable dialysis device is a technique to safely and efficiently regenerate and re-use a small volume of dialysate in a closed-loop system. In a hemodialysis model in goats, we explored whether urea removal by electro-oxidation (EO) could be effectively and safely applied in vivo.
METHODS: A miniature dialysis device was built, containing 1 or 2 'EO unit(s)', each with 10 graphite electrodes, with a cumulative electrode surface of 585 cm2/unit. The units also contained poly(styrene-divinylbenzene) sulfonate beads, FeOOH beads and activated carbon for respective potassium, phosphate and chlorine removal. Urea, potassium and phosphate were infused to create 'uremic' conditions.
RESULTS: Urea removal depended on total electrode surface area (removal of 8±1 and 16±2 mmol/h and clearance of 12±1 and 20±3 mL/min with 1 and 2 EO units, respectively) and plasma urea concentration, but not on flow rate. Extrapolating urea removal with 2 EO units to 24 h would suffice to remove daily urea production, but for intermittent dialysis additional units would be required. EO had practically no effects on potassium and phosphate removal or electrolyte balance. However, slight ammonium release was observed and some chlorine release at higher dialysate flow rates. Minor effects on acid-base balance were observed, possibly partly due to infusion of chloride. Mild hemolysis occurred, which seemed related to urea infusion.
CONCLUSIONS: In conclusion, clinically relevant urea removal was achieved in vivo by electro-oxidation. Efficacy and safety testing in a large animal model with uremia is now indicated.
METHODS: A miniature dialysis device was built, containing 1 or 2 'EO unit(s)', each with 10 graphite electrodes, with a cumulative electrode surface of 585 cm2/unit. The units also contained poly(styrene-divinylbenzene) sulfonate beads, FeOOH beads and activated carbon for respective potassium, phosphate and chlorine removal. Urea, potassium and phosphate were infused to create 'uremic' conditions.
RESULTS: Urea removal depended on total electrode surface area (removal of 8±1 and 16±2 mmol/h and clearance of 12±1 and 20±3 mL/min with 1 and 2 EO units, respectively) and plasma urea concentration, but not on flow rate. Extrapolating urea removal with 2 EO units to 24 h would suffice to remove daily urea production, but for intermittent dialysis additional units would be required. EO had practically no effects on potassium and phosphate removal or electrolyte balance. However, slight ammonium release was observed and some chlorine release at higher dialysate flow rates. Minor effects on acid-base balance were observed, possibly partly due to infusion of chloride. Mild hemolysis occurred, which seemed related to urea infusion.
CONCLUSIONS: In conclusion, clinically relevant urea removal was achieved in vivo by electro-oxidation. Efficacy and safety testing in a large animal model with uremia is now indicated.
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