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clinical practice
Renal-Artery Stenosis
Lance D. Dworkin, M.D., and Christopher J. Cooper, M.D.
This Journal feature begins with a case vignette highlighting a common clinical problem.
Evidence supporting various strategies is then presented, followed by a review of formal guidelines,
when they exist. The article ends with the authors’ clinical recommendations.
* Locations are listed in descending order of likelihood (i.e., ostial is more likely than proximal, which is more likely than
middle).
Regardless of whether hypertension and chron- characteristics are also common in patients with
ic kidney disease are direct consequences of the essential hypertension.28,29 The classic clinical
renovascular lesion, patients with atherosclerotic clues that suggest the diagnosis of renal-artery
renal-artery stenosis are at increased risk for vas- stenosis include the onset of stage 2 hyperten-
cular events. In a retrospective analysis of a Medi- sion (blood pressure >160/100 mm Hg) after 50
care database,2 patients with renal-artery stenosis years of age or in the absence of a family history
had significantly increased rates of chronic kidney of hypertension, hypertension associated with
disease (25%, vs. 2% among those without renal- renal insufficiency (especially if renal function
artery stenosis), coronary artery disease (67% vs. worsens after the administration of an agent that
25%), stroke (37% vs. 12%), and peripheral vascu- blocks the renin–angiotensin–aldosterone sys-
lar disease (56% vs. 13%), after adjustment for tem), hypertension with repeated hospital admis-
other cardiovascular risk factors. Among patients sions for heart failure, and drug-resistant hyper-
with renal arteries that were assessed at the time tension (defined as blood pressure above the goal
of a cardiac catheterization, the incidence of car- despite treatment with at least three drugs of dif-
diovascular events at 4 years of follow-up was ferent classes at optimal doses).
much higher among patients with renal-artery Once renal-artery stenosis is suspected, con-
stenosis than among patients without renal-artery firmation of the diagnosis is typically made by
stenosis, and there was an inverse correlation be- means of imaging (Table 2), since biochemical
tween the severity of stenosis and survival.10 In a tests such as the measurement of plasma renin
cohort of almost 900 patients older than 65 years concentrations lack specificity. Duplex ultrasonog-
of age who were followed prospectively, the pres- raphy is an excellent tool because it is noninva-
ence of renal-artery stenosis was associated with a sive and has no apparent side effects.30 Doppler
risk of a coronary event that was increased by a measurement of renal-artery velocity31 provides a
factor of two, after adjustment for traditional risk functional assessment of the severity of stenosis;
factors. Renal insufficiency in patients with renal- higher velocity correlates with a greater pressure
artery stenosis is also associated with markedly differential across the stenosis (Fig. 1). However,
decreased survival.11 The explanation for the in- duplex imaging is limited by abdominal obesity
creased risk of cardiovascular events among pa- or bowel gas, is technically demanding, and is
tients with renal-artery stenosis is uncertain, but not available at all centers. Alternative methods
it may be related to concomitant atherosclerosis in include MRA and computed tomographic angiog-
other vascular beds,12-18 activation of the renin– raphy (CTA) with the use of high-resolution multi
angiotensin–aldosterone and sympathetic nervous slice detector devices.32 These techniques can
systems, associated renal insufficiency, or all these provide elegant images of the renal arteries and
factors.19-27 the abdominal aorta and can show images in
multiple planes to enhance clarity (Fig. 2). How-
S t r ategie s a nd E v idence ever, equipment, technique, and reconstruction
of the images may affect image quality, as can
Evaluation patient-related factors, including the presence of
The presence of chronic kidney disease, advanced calcium, the presence of stents, and the ability
age, and other atherosclerotic risk factors is as- to hold one’s breath during imaging. In patients
sociated with an increased prevalence of athero- with chronic kidney disease, the use of MRA and
sclerotic renal-artery stenosis; however, these CTA is limited by toxicity of the contrast medium:
nephrogenic systemic fibrosis is associated with patients. Additional agents may include an alpha-
gadolinium,33,34 and nephropathy is associated blocker or beta-blocker, a long-acting calcium-
with iodinated contrast dye. In experienced cen- channel antagonist, and a diuretic. Although a
ters, high-quality digital-subtraction angiography renin–angiotensin–aldosterone system inhibitor
with or without selective renal angiography may may induce acute renal failure in some patients
be performed with the use of small-diameter with bilateral severe stenosis, high-grade steno-
catheters and minimal amounts of contrast mate- sis in one kidney, or advanced chronic kidney
rial in order to reduce the risk of vascular compli- disease,35 the probability of this complication ap-
cations and contrast nephropathy (Table 2). pears to be low, and in most cases, it is reversible
Although the degree of atherosclerosis of the with the discontinuation of treatment. Moreover,
aorta, the size of the kidney, the extent of post- recent data from a large cohort of patients with
stenotic dilatation, and the rapidity of the appear- renal-artery stenosis suggested a reduced risk of
ance and washout of contrast material are use- death among patients treated with an angio-
ful in confirming or ruling out the diagnosis of tensin-converting–enzyme (ACE) inhibitor.36 The
renal-artery stenosis, no tests or findings con- demonstrated benefits of statins and antiplatelet
clusively establish the functional significance of therapy in general populations of patients with
the lesion or predict the response to revascular- atherosclerotic disease provide support for the
ization. Physiological measures such as nuclear use of these agents in patients with renal-artery
scintigraphy, renin sampling from the renal veins, stenosis. Several case reports have described a
determination of pressure gradients across ste reduction in the severity of renal-artery stenosis
noses, or ultrasonographic measurements may be in patients treated with statins, and an association
useful in selected situations to determine whether between statin use and improved survival was re-
a kidney supplied by an occluded renal artery is ported in a large case series of patients with renal-
viable and is likely to be contributing to hyper- artery stenosis who underwent stenting, although
tension or whether stenosis within a renal artery the study design precluded a conclusion that this
is affecting intrarenal pressures. association was causal.37
gioplasty, as compared with medical therapy.42 stenting plus medical therapy with medical ther-
JOB: 36120 ISSUE: 11-12-09
However, the interpretation of these findings, apy alone for the preservation of renal function
individually and in meta-analyses, has been con- showed no significant benefits with the addition
troversial because of issues with patient selec- of stenting.47,48 The larger trial, Angioplasty and
tion, crossover from medical therapy to angio- Stenting for Renal Artery Lesions (ASTRAL) (Cur-
plasty, small samples of patients, and the use of rent Controlled Trials number, ISRCTN59586944),
angioplasty without stenting. Atherosclerotic ste reported elsewhere in this issue of the Journal,49
noses are often ostial, and balloon angioplasty is involved 806 patients with atherosclerotic renal-
suboptimal because of rates of restenosis that may artery stenosis who were randomly assigned to
be as high as 71% when assessed prospectively.43 undergo stent revascularization in addition to re-
The use of stents, which limit elastic recoil, ceiving medical therapy or to receive medical
has led to improved restenosis-free patency as therapy alone. The rate of the primary outcome
compared with angioplasty alone.43 Improved — the change in renal function, as measured by
blood-pressure control after stenting has been the rate of decrease in the reciprocal of the se-
reported in single-center registries,44 as well as rum creatinine level — did not significantly differ
in a multicenter registry of patients who under- between the study groups at the 5-year follow-up.
went stenting after a technically inadequate result Moreover, there were no significant differences
was achieved with balloon angioplasty.45 In a between the groups in mean systolic blood pres-
case series of patients with renal-artery stenosis sure or in rates of renal or cardiovascular events
who underwent revascularization with stents or or death; this was true even in the high-risk
received medications, those who underwent re subgroup of patients with high-grade or bilateral
vascularization had improved survival, improved stenosis or impaired or decreasing kidney func-
blood-pressure control, and less impairment of tion at study entry. However, because the study
renal function.46 included many patients without clinically sig-
A r e a s of Uncer ta in t y
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