Department of Nephrology and Hypertension, University Medical Center Utrecht and Regenerative Medicine Utrecht, Utrecht University , Utrecht , The Netherlands.
Nanodialysis B.V., Oirschot, The Netherlands.
Am J Physiol Renal Physiol. 2018 Nov 1;315(5):F1385-F1397. doi: 10.1152/ajprenal.00094.2018. Epub 2018 Jul 11.
The key to success in developing a wearable dialysis device is a technique to safely and efficiently regenerate and reuse 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. A miniature dialysis device was built, containing 1 or 2 "EO units," each with 10 graphite electrodes, with a cumulative electrode surface of 585 cm per 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. Urea removal was dependent on total electrode surface area [removal of 8 mmol/h (SD 1) and 16 mmol/h (SD 2) and clearance of 12 ml/min (SD 1) and 20 ml/min (SD 3) 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 releasewas 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. 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.
开发可穿戴透析设备的关键在于一种技术,该技术能够在闭环系统中安全有效地再生和再利用小体积的透析液。我们在山羊血液透析模型中探索了电氧化 (EO) 是否可以有效地安全应用于体内。构建了一种微型透析设备,其中包含 1 个或 2 个“EO 单元”,每个单元包含 10 个石墨电极,每个单元的累积电极表面积为 585cm²。这些单元还包含聚苯乙烯-二乙烯基苯磺酸珠、FeOOH 珠和活性炭,分别用于去除钾、磷和氯。输注尿素、钾和磷以产生“尿毒症”条件。尿素的去除取决于总电极表面积[分别使用 1 个和 2 个 EO 单元时,去除率为 8mmol/h(SD1)和 16mmol/h(SD2),清除率为 12ml/min(SD1)和 20ml/min(SD3)]和血浆尿素浓度,但与流速无关。根据 2 个 EO 单元的尿素去除情况推断,如果要去除每天的尿素生成量,则需要 24 小时,但对于间歇性透析,则需要额外的单元。EO 对钾和磷的去除或电解质平衡几乎没有影响。然而,观察到轻微的铵释放,并且在较高的透析液流速下会释放一些氯。观察到酸碱平衡的轻微变化,可能部分是由于氯离子的输注。还观察到轻微的溶血,这似乎与尿素输注有关。总之,体内通过电氧化实现了临床相关的尿素去除。现在需要在尿毒症的大动物模型中进行功效和安全性测试。