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020801 Renal-Artery Stenosis

M E D I C A L P R O G R E S S

N Engl J Med, Vol. 344, No. 6

·

February 8, 2001

·

www.nejm.org

·

431

Review Article

Medical Progress

R

ENAL

-A

RTERY

S

TENOSIS



R

OBERT

D. S

AFIAN

, M.D.,

AND

S

TEPHEN

C. T

EXTOR

, M.D.

From the Division of Cardiology, Department of Medicine, William
Beaumont Hospital, Royal Oak, Mich. (R.D.S.); and the Section on Hy-
pertension and Nephrology, Department of Medicine, Mayo Clinic, Roch-
ester, Minn. (S.C.T.). Address reprint requests to Dr. Safian at William
Beaumont Hospital, Division of Cardiology, 3601 W. 13 Mile Rd., Royal
Oak, MI 48073, or at rsafian@beaumont.edu.

RIMARY diseases of the renal arteries often in-
volve the large renal arteries, whereas secondary
diseases are frequently characterized by small-
vessel and intrarenal vascular disease. In this article,
we will concentrate on the two most common primary
diseases of the renal arteries atherosclerotic renal-
artery stenosis and fibromuscular dysplasia and
their association with two common clinical syndromes,
hypertension and ischemic nephropathy. The relations
among renal-artery stenosis, hypertension, and renal
excretory dysfunction are complex (Fig. 1). Renal-
artery stenosis may occur alone (isolated anatomical
renal-artery stenosis) or in association with hyper-
tension, renal insufficiency (ischemic nephropathy),
or both.

PREVALENCE AND NATURAL HISTORY

Fibromuscular dysplasia is a collection of vascular
diseases that affects the intima, media, and adventitia
(periarterial fibromuscular dysplasia). Fibromuscular
dysplasia accounts for less than 10 percent of cases of
renal-artery stenosis, and 90 percent of cases of fibro-
muscular dysplasia involve the media. Fibromuscular
dysplasia tends to affect girls and women between 15
and 50 years of age, frequently involves the distal two
thirds of the renal artery and its branches, and is char-
acterized by a beaded, aneurysmal appearance on an-
giography (Fig. 2). Intimal and periarterial fibromus-
cular dysplasia is commonly associated with progressive
dissection and thrombosis, whereas medial fibromus-
cular dysplasia progresses in 30 percent of patients and
is rarely associated with dissection or thrombosis. In
contrast to atherosclerotic renal-artery stenosis, fibro-
muscular dysplasia rarely leads to renal-artery occlu-
sion. The cause of fibromuscular dysplasia is unknown,
although many theories have been advanced, includ-
ing those involving a genetic predisposition, smoking,
P

hormonal factors, and disorders of the vasa vasorum
as risk factors.
Atherosclerosis accounts for 90 percent of cases of
renal-artery stenosis and usually involves the ostium
and proximal third of the main renal artery and the
perirenal aorta (Fig. 2C). In advanced cases, segmen-
tal and diffuse intrarenal atherosclerosis may also be
observed, particularly in patients with ischemic ne-
phropathy (Fig. 3). The prevalence of atherosclerotic
renal-artery stenosis increases with age, particularly
in patients with diabetes, aortoiliac occlusive disease,
coronary artery disease, or hypertension.

2-5

Among
patients with atherosclerotic renal-artery stenosis, pro-
gressive stenosis was reported in 51 percent of renal
arteries five years after diagnosis (including 18 per-
cent of initially normal vessels),

6,7

only 3 to 16 percent
of renal arteries became totally occluded,

3,4,6,8

and re-
nal atrophy developed in 21 percent of patients with
renal-artery stenosis of more than 60 percent. Thus,
atherosclerotic renal-artery stenosis is a common and
progressive disease, particularly in patients with dia-
betes or other manifestations of atherosclerosis. Nev-
ertheless, it is likely that many cases of atherosclerotic
renal-artery stenosis are never detected because refrac-
tory hypertension or renal failure does not develop.

RENAL-ARTERY STENOSIS
AND HYPERTENSION

Pathophysiology

The risk of cardiovascular events in adults depends
more on the degree of hypertension than on its cause.
A decrease in renal perfusion pressure activates the
reninangiotensin system, which leads to the release
of renin and the production of angiotensin II; has
direct effects on sodium excretion, sympathetic nerve
activity, intrarenal prostaglandin concentrations, and
nitric oxide production; and causes renovascular hy-
pertension.

9,10

When hypertension is sustained, plasma
renin activity decreases (referred to as reverse tachy-
phylaxis), partially explaining the limitations of renin
measurements for identifying patients with renovas-
cular hypertension.
Although renovascular hypertension often contrib-
utes to accelerated or malignant hypertension, it is not
readily distinguishable from essential hypertension.
Certain classic features, such as hypokalemia, an ab-
dominal bruit, the absence of a family history of es-
sential hypertension, a duration of hypertension of less
than one year, and the onset of hypertension before
the age of 50 years, are more suggestive of renovascular
hypertension than of other types of hypertension,

11

but none have strong predictive value. In fact, the ma-
432

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N Engl J Med, Vol. 344, No. 6

·

February 8, 2001

·

www.nejm.org

Th e Ne w E n g l a nd Jo u r n a l o f Me d ic i ne

jority of patients with renal-artery stenosis who have
hypertension have essential hypertension, as suggest-
ed by the fact that the hypertension usually persists
despite successful revascularization.

Noninvasive Evaluation

Patients with certain clinical features associated with
renal-artery stenosis are often considered for further
evaluation (Table 1). The evaluation may include stud-
ies to assess overall renal function, physiological stud-
ies to assess the reninangiotensin system, perfusion
studies to assess differential renal blood flow, and im-
aging studies to identify renal-artery stenosis (Table
2). Methods of measuring the response of the renin
angiotensin system include renin-sodium profiling, as-
sessment of plasma renin activity before and after the
administration of captopril, assessment of the effect on
blood pressure and renal function of an angiotensin-
convertingenzyme (ACE) inhibitor, and captopril
renography to assess differential renal perfusion. The
tests are not recommended in most elderly patients
with atherosclerotic renal-artery stenosis and hyperten-
sion, since hypertension in these patients is not renin-
dependent and the results do not reliably predict the
course of hypertension after revascularization. In con-
trast, these studies are more useful for identifying pa-
tients with fibromuscular dysplasia in whom hyperten-
sion is likely to be cured by revascularization, since this
disorder is frequently renin-dependent.

12,13

Because of the limited usefulness of physiological
studies in elderly patients with atherosclerotic renal-
artery stenosis, imaging techniques are preferable as a
means to identify stenosis in such patients (Fig. 4).
Duplex ultrasonography can provide images of the re-
nal arteries and assess blood-flow velocity and pressure
waveforms, but there is a 10 to 20 percent rate of fail-
ure due to the operators inexperience or the presence
of obesity or bowel gas.

14

Gadolinium-enhanced mag-
netic resonance angiography and computed tomo-
graphic angiography are useful for evaluating the renal
circulation and aorta, but they are less reliable for vis-
ualizing distal segments and small accessory arter-
ies.

15,16

Gadolinium is not nephrotoxic and is useful in
patients with renal insufficiency.

Figure 1.

Interrelation among Renal-Artery Stenosis, Hypertension, and Chronic Renal Failure.
Renal-artery stenosis may occur alone (isolated anatomical renal-artery stenosis) or in combination with hypertension (renovascular
or essential hypertension), renal insufficiency (ischemic nephropathy), or both. Patients with renal-artery stenosis alone may benefit
from revascularization to prevent loss of renal mass. In patients with renal-artery stenosis and hypertension, hypertension is seldom
cured by revascularization, except in those with fibromuscular dysplasia. In patients with renal-artery stenosis and chronic renal
failure, renal revascularization may improve or stabilize renal function.
Renal-artery
stenosis
Hypertension
Renal-artery
stenosis and
hypertension
Renal-
artery stenosis
and chronic renal
failure
Chronic renal
failure
Renal