Date of Award

6-2024

Document Type

Thesis

Publisher

Santa Clara : Santa Clara University, 2024

Department

Bioengineering

First Advisor

Maryam Mobed-Miremadi

Abstract

Patients with chronic kidney disease (CKD) have lost kidney function. 800,000 Americans have end-stage kidney disease resulting in one of the leading causes of mortality cross-listed with diabetes and heart disease. Over the past decade, the percentage of patients using peritoneal dialysis (PD) has nearly doubled. PD which is a portable treatment involves the insertion of a catheter into the selectively permeable peritoneal cavity infused with a hyperosmolar dialysis fluid drawing the toxins from capillary beds of the peritoneum and into a gravity fed waste solution with a reported clearance of 87%. In order to improve the clearance of the current PD treatment, a kinetic driving force has been proposed to be coupled to the diffusive mechanism, designed for insertion into a custom 3D-printed packed bed reactor. The reactor itself was integrated in turn into a programmable fluidic network to create a custom continuous ambulatory peritoneal dialysis testing device for which the leak-free flow rate was determined to be 30 mL/min. The peritoneum membrane has been simulated using cross-linked alginate fibers ( L = 40 mm, D = 1.6 mm) with an established molecular weight cutoff of 3 nm to which a kinetic layer has been electrostatically-adsorbed encompassing the encapsulated urease. The measured first order kinetic degradation constant was 0.06 min-1 for an initial hyper-uremic urea concentration of 3.2 mg/mL at 20 °C, in a potassium phosphate buffer (pH = 7.0). Using the experimentally derived kinetic results, flow rates and reactor geometry, urea degradation was simulated in the custom device. After a residence time of 3.9 seconds per pass to which an additional 3 seconds should be added for fluid flow across the fluidic network, 165 passes were necessary to achieve a clearance of 87% in 20 min, theoretically half the time of a 40 min existing PD cycle. This projected time improvement does not take into account complications in the fluidic cycle caused by bioerosion at 37 °C in dialysis to be addressed in future studies by anti-swelling strategies.

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