Although arteriovenous fistulae (AVFs) are the preferred mode of dialysis vascular access, over 50% fail to "mature" in that they do not develop an adequate blood flow or diameter to support hemodialysis. This results in a very significant clinical morbidity and economic cost. At a pathogenetic level, AVF maturation failure is due to (a) small vessels (b) "bad" hemodynamics that do not allow for the release of vasodilator molecules such as nitric oxide and (c) abnormal vascular biology due to uremia and oxidative stress. The central hypothesis for this proposal is that the placement of a malleable, coated (drug/cell/gene/chemical), biodegradable maturation enhancing stent (bMES) at the time of AV fistula creation will (a) dilate small veins (b) optimize anatomical configuration in order to improve hemodynamics and (c) improve upon "local" vascular biology as a result of the coated agents. We plan to address this central hypothesis through a series of specific aims that focus on (a) in-vivo degradation profile and toxicity for the bMES (b) in-vivo proof of principle experiments to document efficacy with regard to flow and diameter. We believe that there is a huge unmet clinical need for novel therapies that might enhance AV fistula maturation and that if successful, the concept of bMES could significantly reduce the huge clinical morbidity and economic cost associated with AVF maturation failure.

Public Health Relevance

Although arteriovenous fistulae (AVFs) are the preferred mode of permanent dialysis vascular access, they have huge problems with non-maturation (failure to adequately increase flow and diameter to support dialysis). This proposal investigates the placement of a biodegradable maturation enhancing stent within the venous segment, which could significantly improve AVF maturation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EB016150-02
Application #
8554769
Study Section
Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
Hunziker, Rosemarie
Project Start
2012-09-30
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$185,177
Indirect Cost
$67,302
Name
University of Cincinnati
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Chan, Jenq-Shyong; Campos, BegoƱa; Wang, Yang et al. (2014) Proliferation patterns in a pig model of AV fistula stenosis: can we translate biology into novel therapies? Semin Dial 27:626-32
Campos, Begona; Lee, Timmy; Roy-Chaudhury, Prabir (2013) Arteriovenous fistula failure: is there a role for epigenetic regulation? Semin Nephrol 33:400-6
Saad, Ahmed; Herrmann, Sandra M S; Crane, John et al. (2013) Stent revascularization restores cortical blood flow and reverses tissue hypoxia in atherosclerotic renal artery stenosis but fails to reverse inflammatory pathways or glomerular filtration rate. Circ Cardiovasc Interv 6:428-35
Riella, Miguel C; Roy-Chaudhury, Prabir (2013) Vascular access in haemodialysis: strengthening the Achilles' heel. Nat Rev Nephrol 9:348-57
Rajabi-Jagahrgh, Ehsan; Krishnamoorthy, Mahesh K; Roy-Chaudhury, Prabir et al. (2013) Longitudinal assessment of hemodynamic endpoints in predicting arteriovenous fistula maturation. Semin Dial 26:208-15