Abstract Background and Aims Peritoneal dialysis has important disadvantages, including low plasma clearance and a limited technique survival. A new device for sorbent-assisted continuous flow peritoneal dialysis has been designed (Wearable Artificial KIDney, WEAKID) that is based on continuous recirculation (rapid cycling) of peritoneal dialysate via a single-lumen peritoneal catheter with regeneration of dialysate using sorbents. Anticipated benefits are a better plasma clearance a higher mass transfer area coefficient with continuous flow of dialysate and enhanced diffusion due to a higher time-averaged plasma-dialysate concentration gradient with sorbent-based dialysate regeneration, and a prolonged technique survival thanks to lower peritonitis risk (less (dis)connections) and a lower glucose exposure. Method This is a first-in-human, prospective, open-label, non-randomized, single-arm, multicenter study, that will be performed at the University Medical Center Utrecht (Utrecht, The Netherlands), Università degli studi di Modena e Reggio Emilia (Italy), and Instituto de Investigación Hospital Universitario La Paz, Servicio Madrileño de Salud (Spain). We aim to include 12 stable, adult PD patients. In the first week, blood, urine, and dialysate samples will be collected over three separate days to assess the efficacy of the patient's standard PD schedule. The WEAKID system will then be tested in a clinical setting on 6 days over a period of 2 weeks (three consecutive days per week). During the first week, participants will be treated with WEAKID without sorbents for 4h (first day) or 8h (second and third day). The second week, treatment will consist of WEAKID with sorbents for 4h (first day) or 8h (second and third day). This way, exposure to new components of the system is incremental and the effectiveness of continuous recirculation of dialysate and that the added effect of sorbent-based dialysate regeneration can be analyzed separately. Outcomes The primary aim of this first-in-human clinical trial is to evaluate the (short term) clinical safety and performance of WEAKID treatment in a clinical setting. The primary safety objective will be assessed by describing and examining the incidence of: Key secondary objectives include an evaluation of efficacy in terms of plasma clearance, ultrafiltration, net base release, and patient tolerance. Planning Inclusion of the first patient is expected in January 2024, the final inclusion is expected to take place in November 2024.

Abstract Background and Aims Chronic kidney disease is a growing problem worldwide with a growing number of patients requiring kidney replacement therapy. In recent years we have developed a novel device for peritoneal dialysis (PD), the WEarable Artificial KIDney (WEAKID); composed of a wearable device connected to a dialysate reservoir. WEAKID uses both sorbent technology and continuous flow PD to improve dialysis efficacy. Formative usability testing aids to the identification of design issues that may interfere with a device's safe and effective use and thus may influence decisions made in the design process. Here, we present the results of an international, multicentre, formative usability study of WEAKID among nurses and patients. Method This study used a mixed-methods design and was conducted in hospitals in Italy (Modena University Hospital), Spain (La Paz University Hospital, Madrid), and the Netherlands (University Medical Center Utrecht) between November 2021 and December 2022. An individual, formative usability testing session was conducted with each participant (nurse or patient) under the conditions of simulated use. Participants were asked to perform basic operational procedures (i.e. turning the device on/off, input of dialysis settings, handling an alarm) with the device according to a usability task list. Their performance was observed and use errors (i.e., something that a participant does or fails to do that results in an unexpected or unintended outcome) were noted. Furthermore, participants were asked for feedback, both verbally and by means of completing the system usability scale (SUS), reflecting perceived usability on a scale from 0 (worst) to 100 (best). Results We included 14 participants (n = 6 nurses, n = 8 patients) in three participating centres. All nurses were female and had a median experience with PD of 20.5 years (range 0.5-32). Patients were generally highly educated (n = 5, 63%). In total, 22 use errors occurred, 10 in nurses and 12 in patients. These use errors included factors not related to the device, e.g. not taking appropriate hygiene measures. In particular, use errors occurred during the priming/connection of catheter and handling the alarm. Participants’ feedback mainly concerned the small screen (and thus font) size, user interface (e.g. lack of colour-coded soft buttons), and (short) length of the patient line. The mean SUS score was 70 (range 57.5–85) for nurses, and 71.9 (range 55–87.5) for patients. Conclusion Despite the slightly above-average perceived usability of the device's current design stage, participants made a lot of suggestions for improvements, and usability must be improved to make the device ready for market introduction.

A major challenge for the development of a wearable artificial kidney (WAK) is the removal of urea from the spent dialysate, as urea is the waste solute with the highest daily molar production and is difficult to adsorb. Here we present results on glucose degradation products (GDPs) formed during electrooxidation (EO), a technique that applies a current to the dialysate to convert urea into nitrogen, carbon dioxide, and hydrogen gas. Uremic plasma and peritoneal effluent were dialyzed for 8 hours with a WAK with and without EO-based dialysate regeneration. Samples were taken regularly during treatment. GDPs (glyoxal, methylglyoxal, and 3-deoxyglucosone) were measured in EO- and non-EO-treated fluids. Glyoxal and methylglyoxal concentrations increased 26- and 11-fold, respectively, in uremic plasma (at [glucose] 7 mmol/L) and 209- and 353-fold, respectively, in peritoneal effluent (at [glucose] 100 mmol/L) during treatment with EO, whereas no change was observed in GDP concentrations during dialysate regeneration without EO. EO for dialysate regeneration in a WAK is currently not safe due to the generation of GDPs which are not biocompatible.

A system for sorbent-assisted peritoneal dialysis (SAPD) has been developed that continuously recirculates dialysate via a tidal mode using a single-lumen peritoneal catheter with the regeneration of spent dialysate by means of sorbents. SAPD treatment may improve plasma clearance by the maintenance of a high plasma-to-dialysate concentration gradient and by increasing the mass transfer area coefficient (MTAC) of solutes. The system is designed for daily 8-hr treatment (12 kg, nighttime system). A wearable system (2.3 kg, daytime system) may further enhance the clearance of phosphate and organic waste solutes during the day. Uremic pigs (n = 3) were treated with the day- (n = 3) and nighttime system (n = 15) for 4-8 hr per treatment. Plasma clearance (Cl), MTAC, and total mass transport (MT) of urea, creatinine, phosphate, and potassium were compared with a static dwell (n = 28). Cl, MTAC, and MT of urea, creatinine, phosphate, and potassium were low in the pig as compared to humans due to the pig's low peritoneal transport status and could be enhanced only to a limited extent by SAPD treatment compared with a static dwell (nighttime system: Cl urea: x1.5 (p = .029), Cl creatinine: x1.7 (p = .054), Cl phosphate: x1.5 (p = .158), Cl potassium: x1.6 (p = .011); daytime system: Cl creatinine: x2.7 (p = .040), Cl phosphate: x2.2 (p = .039)). Sorbent-assisted peritoneal dialysis treatment in a uremic pig model is safe and enhances small solute clearance as compared to a static dwell. Future studies in humans or animal species with higher peritoneal transport should elucidate whether our SAPD system enhances clearance to a clinically relevant extent as compared to conventional PD.

A system for sorbent-assisted peritoneal dialysis (SAPD) was designed to continuously recirculate dialysate via a tidal mode using a single lumen peritoneal catheter with regeneration of spent dialysate by means of sorbent technology. We hypothesize that SAPD treatment will maintain a high plasma-to-dialysate concentration gradient and increase the mass transfer area coefficient of solutes. Thereby, the SAPD system may enhance clearance while reducing the number of exchanges. Application is envisaged at night as a bedside device (12 kg, nighttime system). A wearable system (2.0 kg, daytime system) may further enhance clearance during the day. Urea, creatinine, and phosphate removal were studied with the daytime and nighttime system ( n = 3 per system) by recirculating 2 liters of spent peritoneal dialysate via a tidal mode (mean flow rate: 50 and 100 mL/min, respectively) for 8 h in vitro. Time-averaged plasma clearance over 24 h was modeled assuming one 2 liter exchange/day, an increase in mass transfer area coefficient, and 0.9 liters ultrafiltration/day. Urea, creatinine, and phosphate removal was 33.2 ± 4.1, 5.3 ± 0.5, and 6.2 ± 1.8 mmol, respectively, with the daytime system and 204 ± 28, 10.3 ± 2.4, and 11.4 ± 2.1 mmol, respectively, with the nighttime system. Time-averaged plasma clearances of urea, creatinine and phosphate were 9.6 ± 1.1, 9.6 ± 1.7, and 7.0 ± 0.9 mL/min, respectively, with the nighttime system and 10.8 ± 1.1, 13.4 ± 1.8, and 9.7 ± 1.6 mL/min, respectively, with the daytime and nighttime system. SAPD treatment may improve removal of uremic toxins compared with conventional peritoneal dialysis, provided that peritoneal mass transport will increase.

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 cm2 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.

A major challenge for a wearable dialysis device is removal of urea, as urea is difficult to adsorb while daily production is very high. Electro-oxidation (EO) seems attractive because electrodes are durable, small, and inexpensive. We studied the efficacy of urea oxidation, generation of chlorine by-products, and their removal by activated carbon (AC). EO units were designed. Three electrode materials (platinum, ruthenium oxide, and graphite) were compared in single pass experiments using urea in saline solution. Chlorine removal by AC in series with EO by graphite electrodes was tested. Finally, urea-spiked bovine blood was dialyzed and dialysate was recirculated in a dialysate circuit with AC in series with an EO unit containing graphite electrodes. Platinum electrodes degraded more urea (21 ± 2 mmol/h) than ruthenium oxide (13 ± 2 mmol/h) or graphite electrodes (13 ± 1 mmol/h). Chlorine generation was much lower with graphite (13 ± 4 mg/h) than with platinum (231 ± 22 mg/h) or ruthenium oxide electrodes (129 ± 12 mg/h). Platinum and ruthenium oxide electrodes released platinum (4.1 [3.9-8.1] umol/h) and ruthenium (83 [77-107] nmol/h), respectively. AC potently reduced dialysate chlorine levels to < 0.10 mg/L. Urea was removed from blood by EO at constant rate (9.5 ± 1.0 mmol/h). EO by graphite electrodes combined with AC shows promising urea removal and chlorine release complying with Association for the Advancement of Medical Instrumentation standards, and may be worth further exploring for dialysate regeneration in a wearable system.

BACKGROUND:Continuous dialysis could provide benefit by constant removal of potassium and phosphate. This study investigates the suitability of specific potassium and phosphate sorbents for incorporation in an extracorporeal device by capacity and regenerability testing.METHODS:Capacity testing was performed in uraemic plasma. Regenerability was tested for potassium sorbents, with adsorption based on cationic exchange for sodium, with 0.1 M and 1.0 M NaCl. To regenerate phosphate sorbents, with adsorption based on anionic exchange, 0.1 M and 1.0 M NaHCO3 and NaOH were used. Subsequently, sodium polystyrene divinylbenzene sulphonate (RES-A) and iron oxide hydroxide (FeOOH) beads were incorporated in a cartridge for testing in bovine blood using a recirculating blood circuit and a dialysis circuit separated by a high-flux dialyzer (dynamic setup). Preloading was tested to assess whether this could limit calcium and magnesium adsorption.RESULTS:In the batch-binding assays, zirconium phosphate most potently adsorbed potassium (0.44 ± 0.05 mmol/g) and RES-A was the best regenerable potassium sorbent (92.9 ± 5.7% with 0.1 M NaCl). Zirconium oxide hydroxide (ZIR-hydr) most potently adsorbed phosphate (0.23 ± 0.05 mmol/g) and the polymeric amine sevelamer carbonate was the best regenerable sorbent (85.7 ± 5.2% with 0.1 M NaHCO3). In the dynamic setup, a potassium adsorption of 10.72 ± 2.06 mmol in 3 h was achieved using 111 g of RES-A and a phosphate adsorption of 4.73 ± 0.53 mmol in 3 h using 55 g of FeOOH. Calcium and magnesium preloading was shown to reduce the net adsorption in 3 h from 3.57 ± 0.91 to -0.29 ± 1.85 and 1.02 ± 0.05 to -0.31 ± 0.18 mmol, respectively.CONCLUSION:RES-A and FeOOH are suitable, regenerizable sorbents for potassium and phosphate removal in dialysate regeneration. Use of zirconium carbonate and ZIR-hydr may further increase phosphate adsorption, but may compromise sorbent regenerability. Use of polymeric amines for phosphate adsorption may enhance sorbent regenerability. Calcium and magnesium preloading considerably reduced net adsorption of these ions.

Conventional dialysis therapy ofpatients with end-stage renal disease is time-consuming and its discontinuous nature induces physiological stress to the patient. Therefore new emerging approaches facilitate prolonged treatment by using portable devices in home-settings. Such unsupervised treatment calls for continuous automated monitoring of various physiological parameters. This paper highlights the challenges of autonomous personalized renal treatment and presents a leap towards contextaware monitoring in data streams by a physiological modelbased approach. The algorithmic principle is employed to propagate urea concentration, which is measured to assess dialysis efficacy. Simulation results validate the algorithm for the application in a mobile dialysis therapy currently under development. The presented method enables the estimation of medically significant, but technically inaccessible physiological parameters from data stream propagation.