Urea Clearance in a Large-Animal Hemodialysis Benchtop Model Using Nanoporous Silicon Nitride Membranes
- Hemodialysis: Biomarkers, Translational Research
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
- 801 Dialysis: Hemodialysis and Frequent Dialysis
- Ferruzza, Jonathan, University of Rochester Medical Center, Rochester, New York, United States
- Presti, Maria F., University of Rochester Medical Center, Rochester, New York, United States
- Johnson, Dean G., University of Rochester, Rochester, New York, United States
Over three-quarters of a million Americans live with the daily complications of end-stage renal disease (ESRD), and 71% of those are on some form of hemodialysis (NIH NIDDK 2020). One major shortcoming with current hemodialysis is the non-ambulatory nature of the treatment, with many patients undergoing treatment for four hours, three times a week. Our goal is to make conventional renal replacement therapy more compact, allowing for ambulatory dialysis. To accomplish this, our lab has previously devised and utilized nanoporous silicon nitride (NPN) membranes that demonstrated a 20% urea clearance in a small-animal model (Hill et al., 2020). We modified the NPN membranes for use in a large animal benchtop model by increasing the surface area while maintaining a pore size of 0.35-µm. NPN membranes with a pore size of 35-nm were also developed for testing in the large-animal model with the goal of consistent dialysis of uremic toxins without loss of other important macromolecules and blood components (e.g., albumin and white blood cells).
The large-animal hemodialysis benchtop model consists of a 500 mL circulating analyte (20 mM urea-spiked 1x phosphate-buffered saline (PBS) or whole heparinized bovine blood) flowing across an NPN membrane counter to 1x PBS, circulating at a rate of 50 mL/min and 120 mL/min respectively. The NPN membranes are contained in a stable 3D-printed housing unit that allows for effective flow-through and the ability to gather transmembrane pressure readings, without damage to the chip. Small samples (~100 µL) were collected from the body of the dialyzed analyte every five minutes for the first thirty minutes, and every fifteen minutes thereafter, over the course of two hours.
The clearance results of the NPN membranes in the dialysis of urea-spiked 1x PBS and blood show a decrease in urea concentration in the analyte over a time of two hours, consistent with that seen in the small-animal model. This data suggests that NPN membranes are effective dialyzers of metabolic waste products, such as urea, in a large-animal model of ESRD.
This study demonstrates the effectiveness of microporous and nanoporous silicon nitride membranes for dialyzing small metabolic waste products in a large-scale animal model.
- NIDDK Support