Establishment of a Blood Purification System for Renal Failure Rats Using Small‐Size Dialyzer Membranes

Abstract

Hemodialysis techniques for small animals have not been established because no small dialysis apparatus has been available. We recently developed a small-size dialyzer and established an appropriate blood purification system for small animals. To confirm the appropriate dialysate flow rate, bovine blood was dialyzed for 60 min at a fixed blood flow rate of 1.0 mL/min and variable dialysate flow rates. Blood urea nitrogen and creatinine levels decreased significantly at a dialysate flow rate of 5 mL/min (from 13.7 ± 0.2 to 10.3 ± 1.2 mg/dL and 1.07 ± 0.15 to 0.61 ± 0.12 mg/dL, respectively, P < 0.05). To determine the appropriate in vivo conditions, extracorporeal circulation was performed in anesthetized male Sprague-Dawley rats at a dialysate flow rate of 0.0 mL/min, for 240 min, and at variable blood flow rates. Extracorporeal circulation was successful at a blood flow rate of 1.0 mL/min, but not 1.5 mL/min. To establish in vivo hemodialysis conditions, we used the animal model of end stage renal failure. Sprague-Dawley rats were fed a 0.75% adenine-containing diet for 3 weeks, after which they received hemodialysis for 120 min at a dialysate and blood flow rate of 5.0 and 1.0 mL/min, respectively. There were no significant changes in systolic blood pressure or heart rate during dialysis. Thus, this blood purification system can be safely used for small animals at a dialysate flow rate of 5.0 mL/min and a blood flow rate of 1.0 mL/min. This system provides a basis for further research on hemodialysis therapy.

Second Generation Nanoporous Silicon Nitride Membranes for High Toxin Clearance and Small Format Hemodialysis

“…The conventional membranes actually had ≈2 times more area exposed to blood and dialysate when integrated into the devices, but still showed no detectable clearance. Yorimitsu et al saw a ≈25% reduction in urea over 2 h in the same rat model using 4670 mm 2 of polysulfone PSU hemodialysis membrane . This was 20 times the area of PSU that we used in our small‐animal experiments, therefore it is not surprising that we saw no reduction in urea after 4 h. Note that the comparison to Yorimitsu et al directly supports our hypothesis that nanomembranes can reduce the amount of membrane required for hemodialysis by orders of magnitude.…”

“…Yorimitsu et al saw a ≈25% reduction in urea over 2 h in the same rat model using 4670 mm 2 of polysulfone PSU hemodialysis membrane . This was 20 times the area of PSU that we used in our small‐animal experiments, therefore it is not surprising that we saw no reduction in urea after 4 h. Note that the comparison to Yorimitsu et al directly supports our hypothesis that nanomembranes can reduce the amount of membrane required for hemodialysis by orders of magnitude. Even these nonoptimized experiments required ≈1/20 the membrane area to achieve a similar clearance as seen in Yorimitsu et al Additional performance improvements can be expected by adjusting flow rates to optimize clearance and achieving a nonstick coating to eliminate cell adhesion at the device inlet and outlet.…”

“…To test the ability of NPN‐O to reduce toxins in vivo, we employed a uremic rat model and an extracorporeal circuit based on the experiment described by Yorimitsu et al In these experiments, Sprague‐Dawley rats were fed an adenine‐containing diet for two weeks to impair kidney function and to elevate serum urea concentration to more than two times the normal values, then hemodialyzed with an extracorporeal circuit containing the test dialyzer ( Figure a). We conducted the experiments with large area membrane chips featuring multiple membrane windows (Figure b) similar to those we have previously described .…”

“…Using two chips, we created a device with 110 mm 2 active membrane area. By contrast, Yorimitsu et al used 4670 mm 2 of conventional hollow‐fiber PSU dialysis membranes …”

Increasing the removal of protein‐bound uremic toxins by liposome‐supported hemodialysis

“…(20). Each insert was composed of two side-by-side chambers (sample chamber and buffer chamber) separated by an O-ring-sealed vertical cylinder of cellulose dialysis membrane with an 8.0 KDa MWCO.…”