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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01EB021214-01
Application #
8999849
Study Section
Special Emphasis Panel (ZEB1-OSR-B (O1))
Program Officer
Hunziker, Rosemarie
Project Start
2015-09-30
Project End
2019-06-30
Budget Start
2015-09-30
Budget End
2016-06-30
Support Year
1
Fiscal Year
2015
Total Cost
$1,331,543
Indirect Cost
$337,037
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
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