1. What clinical syndromes are associated with renal artery stenosis?

Renovascular hypertension, progressive loss of kidney function from ischemic nephropathy, and recurrent episodes of flash pulmonary edema (meaning acute/abrupt onset pulmonary edema) are the clinical syndromes typically associated with renal artery stenosis. However, renal artery stenosis can also be completely asymptomatic. In the case of renovascular hypertension, hemodynamically significant unilateral orbilateral renal artery stenosis leads to decreased perfusion pressure in one or both kidneys. This stimulates activation of the renin-angiotensin-aldosterone system, which increases systemic pressure to restore kidney perfusion distal to the stenotic lesion(s).

The pathophysiology of ischemic nephropathy is complex and likely relates to activation of multiple pathways triggered by reduced kidney perfusion that promote kidney injury and fibrosis. Flash pulmonary edema in the context of renal artery stenosis tends to occur only with bilateral stenosis (or renal artery stenosis affecting a solitary kidney). In this situation, patients are likely predisposed to episodes of pulmonary edema from enhanced tubular sodium reabsorption and volume expansion from increased renin-angiotensin-aldosterone activity in the absence of a pressure natriuresis phenomenon that would occur within an unaffected kidney.

2. What are the two main causes of renal artery stenosis?

The two important causes of renal artery stenosis are atherosclerosis and fibromuscular dysplasia. Atherosclerotic renal artery stenosis is the more common cause and is often seen in older patients. It occurs in the setting of atherosclerotic disease affecting other vascular beds, such as the coronary, cerebral, and peripheral arterial circulation. These patients often have other risk factors for atherosclerosis, such as diabetes, hypertension, and smoking. In contrast, fibromuscular dysplasia is typically seen in younger female patients.

3. How common is renal artery stenosis?

It depends on the population examined. Some degree of renal artery stenosis will be found incidentally in 19% to 42% of patients with atherosclerotic vascular disease such as coronary artery disease or peripheral vascular disease. Fibromuscular dysplasia causing renal artery stenosis is seen in 3% to 5% of healthy patients being evaluated as potential living kidney donors. In studies examining patients with mild to moderate hypertension, renal artery stenosis has been found in 0.6% to 3% of this population. In patients with refractory hypertension, renal artery stenosis may be found in between 10% and 45% of patients.

4. How often does renal artery stenosis lead to end-stage kidney disease?

In some series of patients receiving dialysis, atherosclerotic renal artery stenosis may lead to end-stage kidney disease in up to 15% of patients. However, in the most recent United States Renal Data Service report, which is a registry that tracks various data on virtually all patients receiving dialysis in the United States, the incidence of renal artery stenosis as the cause for end-stage kidney disease was only 0.6%.

5. Who is at risk of developing renal artery stenosis?

Patients with risk factors for atherosclerotic vascular disease, such as hypertension, dyslipidemia, diabetes, tobacco use, and older age, are at increased risk for atherosclerosis affecting the renal arteries causing stenosis.

6. Who should be screened for renal artery stenosis?

Features suggestive of renal artery stenosis include:

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  Abrupt onset of hypertension at a relatively young age (30 years old) or older age (>50 years old)

  
  
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  Worsening control of previously well treated hypertension

  
  
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  Recurrent episodes of “flash pulmonary edema”

  
  
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  Kidney failure precipitated by initiation of antihypertensive therapy—especially angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)

  
  
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  Unexplained kidney failure

  
  
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  Unilateral atrophic kidney

  
  
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  Abdominal bruit

  
  
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  Unexplained hypokalemia

  
  
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  The presence of atherosclerotic disease in other vascular beds.

7. What diagnostic tests can you use to identify renal artery stenosis? How do you decide which test to use?

Screening for suspected renal artery stenosis can be done with duplex ultrasonography of the renal arteries, computed tomographic angiography (CTA), or magnetic resonance angiography (MRA). Duplex ultrasonography has the advantage of being noninvasive and does not expose patients to potential toxicities of the contrast agents needed for CTA or MRA. However, accuracy of duplex ultrasound is operator dependent and may be limited in patients who are morbidly obese. CTA is noninvasive and can characterize renal artery stenosis with a high degree of sensitivity (as high as 98%) and specificity (as high as 94%). The main disadvantages of this modality are radiation exposure and the need for iodinated contrast, which is potentially nephrotoxic, particularly in patients with impaired kidney function and diabetes. MRA gives exceptional resolution of lesions, causing renal artery stenosis with a very high sensitivity (up to 100%) and specificity (up to 97%), and it has the benefit of not exposing patients to radiation or the risk of contrast nephropathy because gadolinium is used instead of iodinated contrast. Although gadolinium is generally not considered to be a nephrotoxic agent, its use is not without risk. In patients with advanced chronic kidney disease, especially those with end-stage kidney disease, gadolinium has been associated with nephrogenic systemic fibrosis. In addition, MRA is generally a more expensive noninvasive test to evaluate for renal artery stenosis compared with ultrasound and CTA. The gold standard study to diagnose renal artery stenosis is conventional digital subtraction angiography. However, this is an invasive procedure that exposes patients to radiation and iodinated dye in addition to the risk of cholesterol atheroembolic disease (discussed in detail later).

8. What is the resistance index, and how may it be useful in managing renal artery stenosis?

The resistance index is a measure of relative blood flow velocity during systole and diastole within the renal arterial supply using Doppler ultrasonography. It is calculated with the following formula:

It has been shown to correlate with changes in blood pressure following revascularization. Specifically, a high resistance index of >80 suggests extensive atherosclerotic disease of the smaller vessels in the arterial network and is associated with a lack of improvement in blood pressure following revascularization.

9. What is the natural history of renal artery stenosis?

Atherosclerotic renal artery stenosis often progresses anatomically (the degree of stenosis increases over time) and is associated with a high mortality. Numerous studies have documented anatomic progression of atherosclerotic lesions over the course of a few years using various imaging methods. For example, in one study angiographic progression was observed in 11% of patients followed an average of approximately 2.5 years, whereas in another study anatomic progression was seen in 44% of a population followed for slightly longer than an average of 4 years. Patients with fibromuscular dysplasia also may have angiographic progression of their renal artery lesions; 33% of patients with fibromuscular dysplasia in one cohort displayed anatomic progression over an average of about 4 years.

10. What are the long-term outcomes of patients with renal artery stenosis?

Most of the patients with atherosclerotic renal artery stenosis die of cardiovascular disease before ever developing end stage kidney disease (ESKD). Potential reasons for this increased burden of cardiovascular disease in patients with atherosclerotic renal artery stenosis include the presence of atherosclerosis in other vascular beds, excessive activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, and the coexistence of chronic kidney disease. Mortality rates and incidence of ESKD in atherosclerotic renal artery stenosis depend on the populations examined. For example, in some older cohorts, mortality was reported to be as high 32% at 2 years and 45% at 5 years. However, in more recent randomized controlled trials published within the past 10 years Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial, Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, STent placement and blood pressure and lipid-lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery (STAR) trial) comparing medical therapy alone to stenting with medical therapy in patients with atherosclerotic renal artery stenosis, mortality was reported to be approximately 8% at 2 years and then ranged between 14% and 26% over approximately 5 years of follow-up. In contrast, the percentage of patients with atherosclerotic renal artery stenosis requiring dialysis in observational studies ranged from approximately 3% at 2 years to 12% at 5 years. In the more recent randomized controlled trials involving atherosclerotic renal artery stenosis, approximately 2% to 10% of patients with atherosclerotic renal artery stenosis started chronic dialysis over approximately a 5-year period. Kidney failure as a result of fibromuscular dysplasia is felt to be very rare.