A functioning vascular access is critical to provide long-term hemodialysis. Grafts are used as the vascular access in 40-50% of hemodialysis patients. Grafts are prone to recurrent stenosis and thrombosis, requiring frequent radiologic or surgical interventions to maintain their long-term patency for dialysis. Graft thrombosis is usually superimposed on underlying stenosis at the venous anastomosis. The standard approach to clotted grafts is to perform thrombectomy, in conjunction with angioplasty of the underlying stenotic lesion. Unfortunately, the long-term outcomes to this approach are dismal: the median primary (intervention-free) graft patency following thrombectomy is only 1 month. Deployment of stents at the stenotic sites may improve these outcomes by delaying restenosis. The candidate's preliminary research data suggest that stent deployment significant prolongs primary graft patency following thrombectomy, as compared to conventional angioplasty, and that gene polymorphism plays a role in vascular stenosis. The candidate's grant proposes a single-center, clinical randomized trial (CRT), in which patients with a clotted graft with underlying stenosis at the venous anastomosis will be allocated to thrombectomy + angioplasty (control group) or to thrombectomy + angioplasty + stent placement. Information will be collected prospectively on all randomized patients regarding the need for subsequent access procedures, access-related hospitalizations, and access-related complications. The primary endpoint will be primary (unassisted) graft patency. The secondary endpoints will be secondary (assisted) graft patency and overall access-related costs. If the stent arm is statistically superior, then a further study (CRT) will be performed in which patients who will received a stent will be allocated to either placebo or clopidogrel, this will identify if clopidogrel will prolong the primary patency of AV grafts. The candidate also proposes a single-center, prospective clinical trial, in which a genetic polymorphism of heme-oxygenase (HO-1) and 298Asp/-786C variants of eNOS play significant role in the initial stenosis at the venous anastomosis of arteriovenous grafts, in the re-stenosis of the same lesions after percutaneous transluminal angioplasty and after a stent is deployed at this location. The applicant's training will incorporate both didactic training in research methodology, as well as mentored, hands-on experience in performing a randomized clinical trial. His research mentors will be Dr. Michael Allon and Dr. Anupam Agarwal who are experienced investigators with the required expertise in vascular access issues and molecular biology, respectively, to accomplish the goals of this project. The K- 23 grant will enable the applicant to become an independent, funded investigator, with emphasis on clinical research related to vascular access in patients with chronic kidney disease.
Vascular access thrombosis remains a serious problem of long-term hemodialysis care. A functioning vascular access is critical to provide long-term hemodialysis. Grafts are used as the vascular access and are prone to recurrent stenosis and thrombosis, requiring frequent radiologic or surgical interventions to maintain their long-term patency for dialysis. New strategies to enhance vascular access patency and function are need.
| Allon, Michael; Zhang, Li; Maya, Ivan D et al. (2012) Association of factor V gene polymorphism with arteriovenous graft failure. Am J Kidney Dis 59:682-8 |
