Treatment of end stage renal disease (ESRD) patients by renal transplant is severely limited by shortage of donor organs, while dialysis is expensive, inconvenient, and confers significant morbidity and mortality. There are nearly 400,000 people in the US who rely on thrice-weekly, in-center hemodialysis, and collectively, this population consumes over $30 billion annually in Medicare-paid healthcare. The prevalence of ESRD is increasing at 5% per year, and the vast majority of patients are unlikely to ever receive a transplant. We embarked on the development of an implantable artificial kidney (IAK) that combines a hemofilter constructed from silicon nanopore membranes (SNM) with a bioreactor of renal tubule cells to mimic nephronal function. In the final envisioned implementation, blood will be filtered in the hemofilter under circulatory system pressure to remove uremic toxins, salts, small solutes, and water. The resulting ultrafiltrate will then be processed by the bioreactor for volume homeostasis and electrolyte balance. The IAK could serve as a bridge-to-transplant or destination therapy for ESRD. In contrast to kidney transplant, the implantable device will not require the patient to be on immunosuppressive therapy. The proposed Quantum project addresses the advancement of key technologies towards a clinically practical device for long-term operation. One effort will investigate the conditions that optimize the tubule cells to resist phenotypic erosion. The other effort will focus on the design of the mechanically-robust and biocompatible device for ultrafiltration. In subsequent funding cycles, these efforts will be combined to first demonstrate a successful demonstration of the IAK in preclinical testing, and subsequently, first human subjects.
Chronic kidney failure affects over 600,000 Americans and costs the healthcare system over $40 billion annually - more money than the entire budget of the National Institutes of Health. In this project, we plan to use new technologies to engineer an implantable artificial kidney that will not only improve treatment of kidney failure for a greater number of patients, but also reduce overall costs to Medicare.
|Iqbal, Zohora; Moses, Willieford; Kim, Steven et al. (2018) Sterilization effects on ultrathin film polymer coatings for silicon-based implantable medical devices. J Biomed Mater Res B Appl Biomater 106:2327-2336|
|Feinberg, Benjamin J; Hsiao, Jeff C; Park, Jaehyun et al. (2018) Slit pores preferred over cylindrical pores for high selectivity in biomolecular filtration. J Colloid Interface Sci 517:176-181|
|Buck, Amanda K W; Goebel, Steven G; Goodin, Mark S et al. (2018) Original article submission: Platelet stress accumulation analysis to predict thrombogenicity of an artificial kidney. J Biomech 69:26-33|
|Buck, Amanda K W; Groszek, Joseph J; Colvin, Daniel C et al. (2018) Combined In Silico and In Vitro Approach Predicts Low Wall Shear Stress Regions in a Hemofilter that Correlate with Thrombus Formation In Vivo. ASAIO J 64:211-217|
|Ferrell, Nicholas; Cheng, Jin; Miao, Simeng et al. (2018) Orbital Shear Stress Regulates Differentiation and Barrier Function of Primary Renal Tubular Epithelial Cells. ASAIO J 64:766-772|
|Feinberg, Benjamin J; Hsiao, Jeff C; Park, Jaehyun et al. (2017) Silicon nanoporous membranes as a rigorous platform for validation of biomolecular transport models. J Memb Sci 536:44-51|
|Brakeman, Paul; Miao, Simeng; Cheng, Jin et al. (2016) A modular microfluidic bioreactor with improved throughput for evaluation of polarized renal epithelial cells. Biomicrofluidics 10:064106|
|Kensinger, Clark; Karp, Seth; Kant, Rishi et al. (2016) First Implantation of Silicon Nanopore Membrane Hemofilters. ASAIO J 62:491-5|
|Kim, Steven; Feinberg, Benjamin; Kant, Rishi et al. (2016) Diffusive Silicon Nanopore Membranes for Hemodialysis Applications. PLoS One 11:e0159526|