Evidence on continuous flow peritoneal dialysis: A review.

Clinical application of continuous flow peritoneal dialysis (CFPD) has been explored since the 1960s, but despite anticipated clinical benefits, CFPD has failed to gain a foothold in clinical practice, among others due to the typical use of two catheters (or a dual-lumen catheter) and large dialysate volumes required per treatment. Novel systems applying CFPD via the existing single-lumen catheter using rapid dialysate cycling may solve one of these hurdles. Novel on-demand peritoneal dialysate generation systems and sorbent-based peritoneal dialysate regeneration systems may considerably reduce the storage space for peritoneal dialysate and/or the required dialysate volume. This review provides an overview of current evidence on CFPD in vivo. The available (pre)clinical evidence on CFPD is limited to case reports/series with inherently nonuniform study procedures, or studies with a small sample size, short follow-up, and no hard endpoints. Small solute clearance appears to be higher in CFPD compared to conventional PD, in particular at dialysate flows ≥100 mL/min using two single-lumen catheters or a double-lumen catheter. Results of CFPD using rapid cycling via a single-lumen catheter are too preliminary to draw any conclusions. Continuous addition of glucose to dialysate with CFPD appears to be effective in reducing the maximum intraperitoneal glucose concentration while increasing ultrafiltration efficiency (mL/g absorbed glucose). Patient tolerance may be an issue since abdominal discomfort and sterile peritonitis were reported with continuous circulation of the peritoneal dialysate. Thus, well-designed clinical trials of longer duration and larger sample size, in particular applying CFPD via the existing catheter, are urgently required.

Safety of electrooxidation for urea removal in a wearable artificial kidney is compromised by formation of glucose degradation products.

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.

Evaluation of a system for sorbent-assisted peritoneal dialysis in a uremic pig model.

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: ×1.5 (p = .029), Cl creatinine: ×1.7 (p = .054), Cl phosphate: ×1.5 (p = .158), Cl potassium: ×1.6 (p = .011); daytime system: Cl creatinine: ×2.7 (p = .040), Cl phosphate: ×2.2 (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.

In vitro efficacy and safety of a system for sorbent-assisted peritoneal dialysis.

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.