This is an application for a NHLBI Mentored Patient Oriented Research Career Development Award in response to program announcement PA-00-004. This proposal will foster the scientific development of Dr. Matthew Edwards. The proposed career development plan incorporates a multi-disciplinary program of collaboration and mentorship under the direction of Drs. Kimberley Hansen, Charles McCall, and Robert Byington, internationally recognized authorities in the areas of renovascular disease (RVD), investigator development, and the conduct of clinical trials. This plan is designed to create a focused patient-oriented research experience that will provide the foundation for a successful, independent academic career. RVD is a recognized cause of severe secondary hypertension, progressive renal insufficiency, and endstage renal disease among the elderly who are the fastest growing subsegment of both the general and dialysis dependent populations. Angioplasty and stenting (PTAS) of the renal artery has demonstrated beneficial effects with regard to improving blood pressure control. However, a lower rate of improved renal function has been observed. This limitation is critical as renal function response following renal revascularization has been demonstrated to be a major determinant of subsequent cardiovascular morbidity and mortality as well as dialysis free survival. We hypothesize that the low rate of improved renal function is due to embolization of atheromatous debris liberated during the PTAS procedure. To test this hypothesis we propose a prospective, randomized clinical trial of distal embolic protection device (DEP) use during the performance of renal artery PTAS to maximize the renal function response following the procedure. The specific aims of this project will be 1) to examine the safety and efficacy of DEP to improve renal function and blood pressure response following renal artery PTAS and 2) To characterize the atheromatous debris prevented from passage into the kidney through the use of DEP. The public health relevance of this proposal relates to the improvement of a procedure which may be applicable to millions of Americans with the potential to improve renal function (and by extension subsequent survival free of dialysis dependence and adverse cardiovascular events). Currently, up to 45% of individuals undergoing renal artery PTAS experience inferior renal function results to those observed following surgical revascularization. These inferior results likely lead to inferior survival benefit. Therefore, provision of evidence that DEP improves the outcomes of renal artery PTAS has the potential to alter contemporary medical practice and favorably impact the dialysis-free survival for thousands of individuals each year.

K23HL083981

2006-09-10

2011-07-31