A well functioning arteriovenous fistula is the preferred type of vascular access for chronic hemodialysis. In the recent DAC fistula studies we and others observed that fewer than 16% of surgically created fistulas failed due to thrombosis but more than 60% of fistulas failed to reach suitability for dialysis, confirming that impaired maturation is the main obstacle to success after fistula creation. This proposal will address fundamental gaps in knowledge about fistula maturation. The main hypothesis of this proposal is that a combination of anatomic and functional abnormalities of the arterial and venous circulations of the upper extremities predict AV fistula maturation failure in patients with stage 4 and 5 chronic kidney disease. We submit that studies of vascular structure and function can be used to predict fistula maturation. We further hypothesize that vascular calcification in the arm predisposes to fistula maturation failure by impairing vascular distensibility and endothelium-dependent vasodilation. In addition, we propose that augmented sympathetic-mediated vasoconstriction is another factor that contributes to maturation failure of fistulas by preventing the large increases in blood flow necessary in a developing AV fistula. To test these hypotheses we will conduct a prospective observational study of fistula maturation in patients with chronic kidney disease. We will define the natural history of fistula maturation and related clinical and surgical events. We will perform a detailed preoperative evaluation of vessel anatomy, blood flow to the arm and vascular calcifications to identify preoperative predictors of fistula maturation. Finally, early after fistula creation we will evaluate fistula anatomy, blood flow and physical examination findings to develop early postoperative predictors of impaired fistula maturation. Knowledge obtained from the studies in this proposal will help to improve patient selection for AV fistula creation, identify key anatomic and functional predictors of maturation failure, and provide valid data for future intervention trials to promote fistula maturation. A well functioning vascular access is an absolute necessity to provide life-sustaining treatments for patients on hemodialysis AV fistulas are the best type of vascular access for dialysis, but unfortunately, most fistulas fail to develop adequately to sustain dialysis treatments. This proposal aims to identify predictors of fistula failure so that appropriate interventions to improve success can be implemented in the future.