Renal Artery Atherosclerosis
Jose D. Tafur
Christopher J. White
INTRODUCTION
Atherosclerotic renal artery stenosis (ARAS) is an important cause of secondary hypertension. It also threatens renal function and increases the risk of cardiovascular decompensation syndromes such as acute coronary syndromes and flash pulmonary edema.1,2 Understanding the pathophysiology and clinical manifestation of ARAS is crucial in optimizing care for patients with the condition. In each individual with ARAS, it is important to determine whether it is hemodynamically significant and causing a clinical problem such as uncontrolled hypertension, fluid retention, or renal insufficiency.
Epidemiology
It is estimated that about 7% of individuals older than age 65 years have ARAS.3 An autopsy series showed ARAS with greater than or equal to 50% luminal diameter narrowing (ie, stenosis) in 27% of patients older than 50 years and 53% of patients with prior history of diastolic hypertension.4 Another autopsy series found that 8% of patients with diabetes and 10% of patients with both diabetes and hypertension had evidence of ARAS.5 Coronary artery disease, hypertension, diabetes, smoking, and age are associated with an increased prevalence of ARAS. The strongest predictor of ARAS is the presence of atherosclerotic peripheral vascular disease (PAD).2
Risk Factors
The patient with ARAS frequently has atherosclerotic vascular disease involving other vascular beds such as the coronaries, lower extremities, and carotids. A study to determine the prevalence of ARAS in patients with atherosclerosis elsewhere found ARAS—defined as greater than 50% renal artery diameter stenosis—in 38% of subjects with an abdominal aortic aneurysm and 39% of those with PAD. Another multicenter cohort study evaluated the association of ARAS with age, gender, and other potential risk factors among participants in the cardiovascular health study (CHS). ARAS (≥60% stenosis) was found in 6.8% of study participants, including 5.5% women and 9.1% of men (P = 0.053). ARAS was found in 6.9% of white and 6.7% of African American participants (P = 0.993).3
ARAS represents more than 90% of all causes of renal artery stenosis (RAS). It predominantly affects patients of advanced age and those with other risk factors for atherosclerotic disease (diabetes, dyslipidemia, and tobacco use).6 ARAS may be unilateral or bilateral, usually involving the ostium and more proximal segments of the renal arteries.
PATHOGENESIS
Neurohormonal activation from unilateral or bilateral renal hypoperfusion will result in renin release, an early stimulator in the renin-angiotensin-aldosterone system (RAAS).7,8 When hypoperfusion occurs, the ischemic kidney releases renin from juxtaglomerular cells. Renin stimulates the release of angiotensin I, which is converted to angiotensin II by angiotensin-converting enzyme (ACE) in the pulmonary endothelium. In unilateral ARAS, this neurohormonal activation will lead to vasoconstriction and pressure diuresis of the unaffected kidney known as pressure natriuresis; this prevents systemic volume overload causing hypertension and hyponatremia. Angiotensin II also stimulates the release of antidiuretic hormone from the posterior pituitary gland, stimulating the release of aldosterone from the adrenal cortex. Aldosterone exerts effects on the renal tubules, causing more sodium and water retention. With bilateral (or solitary ARAS with a single functioning kidney), the lack of natriuresis leads to fluid and sodium retention, resulting in congestive heart failure (CHF).9
Ischemic nephropathy occurs in severe ARAS when there is a significant decrease in renal cortical oxygenation that leads to excretory dysfunction. There are several mechanisms explaining how a hemodynamically significant lesion ultimately results in interstitial fibrosis.10 By one pathway, recurrent local ischemia causes tubulointerstitial injury and microvascular damage, which contributes to oxidative injury, increased production of fibrogenic cytokines, and inflammation that eventually leads to atrophy and fibrosis. In moderate ARAS, renal cortical and medullary oxygenation are preserved by a compensatory decrease in oxygen consumption.11
CLINICAL PRESENTATION
Common Signs and Symptoms
The main clinical syndromes associated with hemodynamically significant ARAS include renovascular hypertension, ischemic nephropathy, and/or cardiac destabilization syndromes.
Renovascular Hypertension
Resistant (refractory) hypertension is defined as blood pressure (BP) above goal on three different classes of antihypertensive medications, ideally including a diuretic drug.12,13 Patients
with resistant hypertension should be evaluated for secondary causes of hypertension. Studies of resistant hypertension commonly reveal a high prevalence of previously unrecognized renovascular disease, particularly in older patients. In patients older than 50 years of age who were referred to a hypertension center, 13% had a secondary cause of hypertension, the most common of which was ARAS.6
with resistant hypertension should be evaluated for secondary causes of hypertension. Studies of resistant hypertension commonly reveal a high prevalence of previously unrecognized renovascular disease, particularly in older patients. In patients older than 50 years of age who were referred to a hypertension center, 13% had a secondary cause of hypertension, the most common of which was ARAS.6
Ischemic Nephropathy
ARAS is a potentially reversible form of renal insufficiency. However, if unrecognized, it can lead to end-stage renal disease (ESRD). Some studies suggest that 11% to 14% of ESRD is attributable to chronic ischemic nephropathy from ARAS.15 Favorable predictors of improvement with renal revascularization include a rapid recent increase in serum creatinine concentration, decrease in glomerular filtration rate (GFR) during angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) treatment, absence of glomerular or interstitial fibrosis on kidney biopsy, and kidney pole-to-pole length greater than 8.0 cm.16 In 73 patients with chronic renal failure (creatinine clearance <50 mL/min) and clinical evidence of renal vascular disease and a mean follow-up of 2 years, renal function improved in 34 of 59 patients (58%). The most important predictor of improvement was the slope of the reciprocal serum creatinine plot before revascularization, suggesting that rapidly progressive renal failure is associated with a more favorable response after revascularization in patients with vascular nephropathy and ARAS.17
Cardiac Destabilization Syndromes
Exacerbations of coronary ischemia and CHF caused by increased systemic vasoconstriction and/or volume overload can be attributed to ARAS. The most widely recognized example of a cardiac destabilization syndrome is “flash” pulmonary or Pickering syndrome.1,18 Renovascular disease may also complicate the treatment of patients with heart failure by preventing the administration of angiotensin antagonist therapy (ie, ACEI or ARB worsening kidney function because of a decrease in renal perfusion pressure).
The importance of renal artery revascularization in the treatment of cardiac disturbance syndromes has been described in a series of patients presenting with either CHF or an acute coronary syndrome.19 Successful renal stent placement resulted in a significant decrease in BP and symptom improvement in 88% (42 of 48) of patients. For those patients who presented with unstable angina, renal artery stenting improved the Canadian Class Society (CCS) symptoms at least by one class, independent of concomitant coronary intervention. In patients presenting with CHF, the New York Heart Association (NYHA) Class of symptoms improved by at least one, also independent of coronary revascularization. Among 207 patients with decompensated CHF, 19% had severe ARAS and underwent renal artery stenting with a decreased frequency of CHF admissions, flash pulmonary edema, reduced NYHA Class symptoms, and tolerance to ACEI.20
Differential Diagnosis
Understanding the pathophysiology and clinical manifestations of ARAS is crucial when developing an appropriate differential diagnosis for resistant hypertension. Essential hypertension, other causes of secondary hypertension, and other causes of worsening renal function can coexist. When ARAS is detected, it is very important to determine whether it is hemodynamically significant and causing a clinical problem such as resistant hypertension, CHF, or renal insufficiency, because nonobstructive ARAS may be an innocent bystander. Importantly, not all patients with ARAS will develop a clinical syndrome, and, certainly, only a minority of patients with hypertension and/or CHF have ARAS.
Besides atherosclerosis, other conditions may result in RAS. Fibromuscular dysplasia is the cause in 10% to 30% of patients with RAS, most commonly affecting women younger than 50 years of age and typically involving the middle and distal main renal artery or the intrarenal branches. Other less common causes (<10%) of RAS include thromboembolic disease, arterial dissection, infrarenal aortic aneurysm, vasculitis (ie, Takayasu arteritis, Buerger disease, polyarteritis nodosa, and post radiation), neurofibromatosis type 1, and retroperitoneal fibrosis.
DIAGNOSIS
There are multiple diagnostic modalities available for the diagnosis of ARAS. According to the American College of Cardiology/American Heart Association (ACC/AHA) clinical practice guidelines, magnetic resonance angiography (MRA), computed tomographic angiography (CTA), and duplex ultrasonography (DUS) all receive a class I indication (level of evidence B) as a screening test to establish ARAS.13 When the clinical suspicion is high for ARAS and the result of the noninvasive test is inconclusive, catheter angiography is then recommended for screening. Each diagnostic test has its own advantages and disadvantages, allowing physicians to have different approaches to different patients (Figure 82.1).
Doppler Ultrasound Evaluation
Renal artery Doppler ultrasound, or DUS, is useful for screening for ARAS. It carries a sensitivity of 84%, specificity of 97%, and positive predictive value of 94% for the detection of significant ARAS.21 The accuracy of this test is highly dependent on the technicians’ skill in performing the examination.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
