US Pharm. 2015;40(8):HS-16-HS-19.
It has been reported that renal artery stenosis (RAS) is a major cause of renovascular hypertension (RVH). Between 1% and 10% of the 50 million people in the United States with hypertension have or have had RAS.1
Not only does RAS play a role in the pathogenesis of hypertension, it is also increasingly recognized as an important cause of chronic renal insufficiency and end-stage renal disease (ESRD). The most common etiology of RAS is believed to be atherosclerosis, especially in the elderly. RAS progressively decreases blood flow to the kidneys and, eventually, impacts renal function and kidney structure.1
With the increase in the elderly population and the possibility of RAS and ischemic nephropathy, clinicians are looking for noninvasive diagnostic tools and effective therapeutic measures to successfully resolve this problem. In this article, we explore the pathophysiology of this disorder, its signs and symptoms, its complications, and the invasive and noninvasive diagnostic procedures for reversing renal artery occlusion.1
The prevalence of RVH is probably less than 1% in patients with mild hypertension, but may be as high as 10% to 40% in patients with acute, severe, or refractory hypertension.1
PATHOPHYSIOLOGY
RAS is primarily caused by atherosclerosis, or clogging, narrowing, and hardening of the renal arteries. In these cases, RAS develops when plaque builds up on the inner wall of one or both renal arteries, making them hard and narrow.2
Renal blood flow is three to four times greater than the perfusion to other organs due to the need to perform glomerular filtration. In patients with RAS, the chronic insufficiency produced by the obstruction of renal blood flow leads to kidney changes that are more pronounced in the tubular tissue. These include inflammation, fibrosis, tubulosclerosis, and intrarenal arterial thickening.2
In patients with RAS, when renal perfusion pressure drops below 70 mmHg to 85 mmHg, the autoregulation system between the afferent and efferent arteries can fail to maintain the glomerular filtration rate (GFR). This will lead to a decrease in the GFR, but will not likely be observed until arterial luminal narrowing exceeds 50%.2
There is currently no formal recommendation for when to intervene surgically or radiologically in RAS. It is reported that a ratio of pressure less than 90%, measured distal to renal artery stenosis relative to aortic pressure, was associated with significant renin release from the affected kidney. This might be useful as a functional measurement of significant renovascular stenosis leading to hypertension and, thus, a marker of a greater likelihood of benefit from angioplasty and stenting.1,2
The other main cause of RAS is fibromuscular dysplasia (FMD)—the abnormal development or growth of cells on the renal artery walls—which can cause blood vessels to narrow.3
SIGNS AND SYMPTOMS
In many cases, RAS has no symptoms until it becomes severe. The sign of RAS is usually either high blood pressure or decreased kidney function, or both, but RAS is often overlooked as a cause of hypertension. RAS should be considered as a cause of high blood pressure in people who are aged >50 years when they develop high blood pressure or have a marked increase in blood pressure, have no family history of high blood pressure, and cannot be successfully treated with at least three or more different types of hypertension medications.4
Important symptoms include increased or decreased urination, edema, swelling (usually in the legs, feet, or ankles and less often in the hands or face), generalized itching or numbness, nausea and vomiting, and muscle cramps.4
RISK FACTORS
People at risk for atherosclerosis are also at risk for RAS. Risk factors for RAS caused by atherosclerosis include high blood cholesterol levels; high blood pressure; smoking; lack of physical activity; a diet high in fat, cholesterol, sodium, and sugar; male gender aged >45 years or female aged >55 years; and a family history of early heart disease.3
The risk factors for RAS caused by FMD are unknown, but FMD is most common in women and people 25 to 50 years of age.3 FMD can affect more than one person in a family, indicating that it may be caused by an inherited gene.3
COMPLICATIONS
People with RAS are at increased risk for complications resulting from loss of kidney function or atherosclerosis occurring in other blood vessels, such as chronic kidney disease (CKD), coronary artery disease, stroke, and peripheral vascular disease.
RAS can lead to kidney failure, described as ESRD that requires blood-filtering treatments (dialysis) or kidney transplantation, though such failure is uncommon in people who receive ongoing treatment for RAS.5
DIAGNOSIS
RAS can be diagnosed by listening to the abdomen with a stethoscope and through imaging tests conducted by a specialist. When blood flows through a narrow artery, it sometimes makes a special sound, called a bruit. Physicians may place a stethoscope on the front or side of the abdomen to listen for this sound. The absence of this sound, however, does not exclude the possibility of RAS.
In some cases, RAS has been found during coronary angiography for diagnosis of heart problems. Coronary angiography uses a contrast medium and x-rays to visualize how blood flows through the heart. There are four well-known imaging techniques for the diagnosis of RAS, as follows:
Catheter Angiogram: Traditional angiography is a special kind of x-ray in which a catheter is sent through the large arteries, often from the groin into the renal artery. The procedure is performed by a radiologist in an outpatient center or hospital without anesthesia, although a sedative may be given to lessen anxiety. This technique uses a contrast medium injected through the catheter so that the renal artery shows up more clearly on the x-ray. Catheter angiography is the gold standard for diagnosing RAS owing to the high quality of the image produced. In addition, severe RAS can be treated during the same visit. This procedure is invasive and more expensive than other imaging tests.6
Duplex Ultrasonography: Duplex ultrasonography is a combination of traditional ultrasound and Doppler ultrasonography and is a noninvasive, low-cost procedure. Ultrasound uses a transducer that bounces safe, painless sound waves off organs to create an image of their structure. Doppler ultrasonography records sound waves reflected off moving objects, such as blood, to measure their speed and other aspects of how they flow. This procedure is performed by a special technologist in an outpatient center or hospital, and a radiologist interprets the images. No anesthesia is required. The images can show blockage in the renal artery or movement of blood through nearby arteries at lower than normal speed.7
Computed Tomography Angiography (CTA): This technique uses a combination of computer technology and x-rays to produce images. As in the above techniques, no anesthesia is required, and the test is performed by a radiologist and radio-technologist in a hospital. A contrast medium is injected into a vein in the patient’s arm to better see the structure of the arteries. The patient lies on a table that slides into a tunnel-shaped device where the x-rays are taken. CTA is less invasive and faster than catheter angiography; however, it is not recommended in cases of poor kidney function owing to the risk of x-ray radiation and the requirement for larger amounts of contrast medium.8
Magnetic Resonance Angiography (MRA): This technique can provide a functional assessment of blood flow and organ function. It uses radio waves and magnets to produce detailed pictures of the body’s internal organs and soft tissues without using x-rays. Anesthesia is not required, though light sedation may be used for people with a fear of small spaces. With most MRA scans, the patient lies on a table that slides into a tunnel-shaped apparatus that may be open-ended or closed at one end. As with CTA, the use of contrast medium with an MRA is not advised for patients with poor kidney function. This is because of the risk of complications to the skin and other organs, as the compromised kidneys may not remove the contrast medium well enough.9
TREATMENT
Treatment for RAS aims to prevent it from getting worse, treat RVH, and relieve the blockage of the renal arteries. This can be achieved with lifestyle changes, medications, and, finally, surgery.
If RAS has not led to RVH or a significant artery blockage, it may not require treatment. According to the American Heart Association, RAS that has caused more than 60% reduction in the diameter of the renal artery must be treated. However, it is not yet clear what degree of blockage will cause significant problems.10
Lifestyle Changes
The first step in treating RAS is to make lifestyle changes that promote healthy blood vessels throughout the body, including the renal arteries. The best way to keep plaque from building up in the arteries is to exercise, maintain a healthy body weight, and choose healthy foods. People who smoke should quit in order to help protect their kidneys and other internal organs.
Patients with RAS that has caused decreased kidney function should limit their intake of protein, cholesterol, sugar, sodium, and potassium to slow the progression of kidney failure. Limiting intake of these foods can help prevent atherosclerosis, which, as discussed, can lead to RAS.
The National Kidney and Urologic Diseases Information Clearinghouse has two helpful guidelines on its website (www.niddk.nih.gov/health-information): Nutrition for early Chronic Kidney Disease in Adults and Nutrition for Advanced Chronic Kidney Disease in Adults.
Medications
Two types of blood pressure–lowering medications, ACE inhibitors and angiotensin receptor blockers (ARBs), have proven effective in slowing the progression of hypertension and kidney disease. However, many people require more than two medications to control their blood pressure. So, a diuretic, a beta-blocker, a calcium channel blocker, and other blood pressure medications may also be needed. Some patients with RAS cannot take an ACE inhibitor or ARB owing to its effects on the kidneys. Those with RAS who are prescribed an ACE inhibitor or ARB should have their kidney function checked within a few weeks of starting the medication and be in close contact with their physician.11
In addition, a cholesterol-lowering medication to prevent plaque from building up in the arteries and a blood thinner, such as aspirin, to help the blood flow more easily through the arteries may also be prescribed.
Surgery
Recent research has indicated that surgery for treatment of RAS due to atherosclerosis has not improved outcomes compared with medication. However, surgery may be recommended for patients with RAS caused by FMD or RAS that does not improve with medication. The following procedures are performed under anesthesia in a hospital by a vascular surgeon who specializes in repairing blood vessels.12
Angioplasty and Stenting: Angioplasty is a procedure in which a catheter is inserted in the renal artery, usually through the groin, just as in catheter angiography. In addition, for angioplasty, a tiny balloon at the end of the catheter can be inflated to flatten the plaque against the artery wall. A stent may then be placed inside the artery to keep the plaque flattened and the artery open. Patients with RAS caused by FMD may be successfully treated with angioplasty alone, while angioplasty with stenting has a better outcome for those suffering from RAS caused by atherosclerosis.
Endarterectomy or Shunting: In endarterectomy, the plaque is cleaned out of the artery, leaving the inside lining smooth and clear. To create a shunt, or bypass, a vein or synthetic tube is used to connect the kidney to the aorta. This new path serves as an alternate route for blood to flow around the blocked artery into the kidney. These procedures are not performed as often as in the past because of a high risk of complications during and after the procedure.
REFERENCES
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2. NINDS Fibromuscular Dysplasia Information Page. www.ninds.nih.gov/disorders/fibromuscular_
dysplasia/fibromuscular_dysplasia.htm. Updated June 23, 2011. Accessed April 11, 2015.
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7. Radermacher J, Chavan A, Bleck J, et al. Use of Doppler ultrasonography to predict the outcome of therapy for renal-artery stenosis. N Engl J Med. 2001;344:410-417.
8. Cooper CJ, Murphy TP, Cutlip DE, et al. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med. 2014;370:13-22.
9. Turgutalp K, Kiykim A, Ozhan O, et al. Comparis on of diagnostic accuracy of Doppler USG and contrast-enhanced magnetic resonance angiography and selective renal arteriography in patients with atherosclerotic renal artery stenosis. Med Sci Monit. 2013;19:475-482.
10. Zeller T, Sixt S, Rastan A, et al. Treatment of reoccurring instent restenosis following reintervention after stent-supported renal artery angioplasty. Catheter Cardiovasc Interv. 2007;70:296-300.
11. Hackam DG, Duong-Hua ML, Mamdani M, et al. Angiotensin inhibition in renovascular disease: a population-based cohort study. Am Heart J. 2008;156:549-555.
12. Libertino JA, Beckmann CF. Surgery and percutaneous angioplasty in the management of renovascular hypertension. Urol Clin North Am. 1994;21:235-243.
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