Renal artery disease includes a group of disorders affecting renal blood flow. Causes of impaired renal blood flow include atherosclerosis, fibromuscular dysplasia, dissection, and trauma. Atherosclerosis is the most common cause of renal artery stenosis (RAS). RAS may be responsible for poorly controlled hypertension and impaired renal excretory function (azotemia). Population-based studies report a prevalence of approximately 7 % in individuals greater than age 65 [1]. In selected populations suffering from peripheral vascular disease, carotid stenosis, and aortoiliac disease the prevalence of RAS may be as high as 40–50 % [2, 3].

In 1937, Goldblatt caused hypertension, azotemia, and renal atrophy in a canine model with iatrogenic unilateral RAS [4]. Nephrectomy soon became the treatment of choice for renovascular hypertension until a 1956 review of 575 patients revealed a disappointing cure rate of 25 % [5]. Freeman performed transaortic renal endarterectomy in 1954 [6], but a review of results using this technique documented cure in less than half of patients.

RAS may manifest clinically as hypertension or renal insufficiency. In general, hypertension directly caused by RAS is associated with refractory, poorly controlled hypertension. Refractory hypertension is defined as at least three classes of maximally dosed antihypertensives—one of which is a diuretic agent.

The degree of azotemia associated with RAS varies from absent to severe owing to associated comorbidities such as diabetes, which may contribute to impaired renal function.

In the early period following the development of hemodynamically significant RAS, the renin-angiotensin-aldosterone (RAA) system is responsible for the body’s physiologic response to RAS. Renin produced by the juxtaglomerular cells converts angiotensinogen to angiotensin I. Angiotensin I is converted to angiotensin II (ATII) by angiotensin converting enzyme (ACE). ATII is a potent local and systemic vasoconstrictor. ATII acts on the adrenal gland to promote aldosterone production. Aldosterone is an important mediator of renal tubular sodium absorption and volume expansion. This compensatory effect on volume expansion explains the unexpected worsening in renal function when a patient with bilateral RAS is started on an ACEI or ARB agent. Over time, RAS-mediated volume expansion contributes less to hypertension; it appears that systemic arterial medial wall hyperplasia remodeling is responsible for maintenance of hypertension.

Although commonly believed that the sole reason for intervening upon RAS is to improve perfusion and halt or improve renal dysfunction, the goals of intervention deserve special attention. Although improvement of renal function or cessation of decline (and thus avoidance of renal replacement) is a laudable clinical benefit, the global focus should be a collective reduction of cardiovascular events (MI, heart failure, and stroke). Selection of the ideal population that benefits from renal revascularization has, and continues to be, the ongoing clinical challenge.