Transcript causal relationship exists between anatomically evident arterial

Renal Artery Stenosis
Resident’s conference
Presented by: Gagandeep K Heer, MD
(PGY-2)
Background
• Renal artery stenosis (RAS) is the major cause of renovascular
hypertension and it accounts for about 1-10% of the 50 million people
in the United States who have hypertension. The incidence is less than
1% of cases of mild to moderate HTN. However, it rises to 10 to 45 %
in patients with acute (or superimposed upon a preexisting elevation in
blood pressure), severe, or refractory hypertension.
• Renovascular hypertension (RVHT) denotes nonessential hypertension
in which a causal relationship exists between anatomically evident
arterial occlusive disease and elevated blood pressure. RVHT is the
clinical consequence of renin-angiotensin-aldosterone activation as a
result of renal ischemia.
• RAS is also being increasingly recognized as an important cause of
chronic renal insufficiency and end-stage renal disease. Studies suggest
that ischemic nephropathy from RAS may be responsible for 5-22% of
advanced renal disease in all patients older than 50 years in US.
Causes of RAS
Major causes of the renal arterial lesions are:
• Atherosclerosis —It is the cause of RAS in >2/3rd of the cases. This
primarily affects men over the age of 45 and usually involves the aortic
orifice or the proximal main renal artery. This disorder is particularly
common in patients with diffuse atherosclerosis, but can occur as a
relatively isolated renal lesion.
• Fibromuscular dysplasia — In comparison to atherosclerosis,
fibromuscular dysplasia most often affects younger women and
typically involves the distal main renal artery or the intrarenal
branches.
• Other less common causes of RAS include:
Vasculitis (Takayasu’s arteritis)
Dissection of the renal artery.
Thromboembolic disease
Renal artery aneurysm
Renal artery coarctation
Extrinsic compression
Radiation injury
Pathophysiology
Atherosclerotic RAS
• The initiator of endothelial injury is not clear; however, dyslipidemia,
hypertension, cigarette smoking, diabetes mellitus, viral infection,
immune injury, and increased homocysteine levels may contribute to
endothelial injury.
• In the atherosclerotic lesion site, endothelium permeability to plasma
macromolecules (e.g. LDL) increases, turnover of endothelial cells and
smooth muscle cells and intimal macrophages also increases. When
atherogenic lipoproteins exceed certain critical levels, the mechanical
forces may enhance lipoprotein insudation in these regions, leading to
early atheromatous lesions. The sites where the initial atherosclerotic
lesions developed are more prone to physiological adaptation to
mechanical stress secondary to variations in flow and wall tension (e.g.
renal artery site).
Pathophysiology
Fibromuscular dysplasia:
• Fibromuscular dysplasias are uncommon
angiopathies associated with heterogeneous
histologic changes that may affect the carotid
circulation as well as the visceral and peripheral
arteries.
• String of beads is the classic radiographic finding
seen in FMD.
• FMD, as a cause of RAS usually affects young to
middle-aged adults, mostly women, but it can also
affect children.
Pathophysiology
• Renal blood flow is 3 to 5 fold greater than the perfusion to other
organs because it drives glomerular capillary filtration. Both
glomerular capillary hydrostatic pressure and renal blood flow are
important determinants of the glomerular filtration rate (GFR).
• In patients with RAS, the GFR is dependent on angiotensin II and
other modulators that maintain the autoregulation system between the
afferent and efferent arteries and can fail to maintain the GFR when
renal perfusion pressure drops below 70-85 mm Hg. Significant
functional impairment of autoregulation, leading to a decrease in the
GFR, is not likely to be observed until arterial luminal narrowing
exceeds 50%.
• RVHT develops as a result of increased renin and angiotensin II levels
causing vasoconstriction as well as salt and water retention (volume
expansion) due to increased aldosterone level.
Pathophysiology
• Increased secretion of renin accelerates the conversion of angiotensin
I to angiotensin II which enhances the adrenal release of aldosterone.
• Angiotensin II causes vasoconstriction of both afferent and efferent
arterioles, with a preferential affect on the efferent side. Under
physiologic conditions, efferent tone is essential to maintain
intraglomerular pressure.
• In a kidney rendered ischemic by RAS with a reduced afferent blood
flow, the intraglomerular pressure and glomerular filtration are
maintained by angiotensin II–mediated efferent vasoconstriction.
Removal of the efferent vasoconstriction effect by using angiotensin
blockade (e.g. by using ACEI) may reduce GFR by causing decrease
in intraglumerular pressure.
• In patients with RAS, the chronic ischemia produces adaptive
changes in the kidney that are more pronounced in the tubular tissue.
These changes include atrophy with decreased tubular cell size,
patchy inflammation and fibrosis, tubulosclerosis, atrophy of the
glomerular capillary tuft, thickening and duplication of the Bowman
capsule, and intrarenal arterial medial thickening.
Demographics
• Race: RVD is less common in African American patients. The
incidence rate in 2 studies of patients with severe hypertension was 2745% in whites compared to 8-19% in African Americans.
• Sex: While the incidence of atherosclerotic RVD is independent of sex,
Crowley et al showed that female sex (as well as older age, elevated
serum creatinine level, coronary artery disease, peripheral vascular
disease, hypertension, and cerebrovascular disease) is an independent
predictor of RVD progression.
• Age: The incidence of RAS increases with increasing age.
In 1964, Holley et al reported data from 295 consecutive
autopsies performed in their institution during a 10-month period. The
mean age at death was 61 years. In the whole group, the prevalence
rate of RAS was 27% of 256 cases identified as having history of
hypertension. 56% of these showed significant stenosis (>50% luminal
narrowing). Among normotensive patients, the incidence of severe
RAS was 17%. Among those older than 70 years, 62% had severe
RAS.
Another study reported similar results, showing 18% incidence of
severe RAS for patients aged 65-74 years and 42% for patients older
than 75 years.
Clinical Findings
• Difficult-to-control hypertension despite adequate medical
treatment
• Hypertension with renal failure or progressive renal
insufficiency
• Accelerated or malignant hypertension
• Severe hypertension (diastolic blood pressure >120 mm
Hg) or resistant hypertension
• Hypertension with an asymmetric kidney
• Paradoxical worsening of hypertension with diuretic
therapy
• Onset of hypertension occurring in patients younger than
30 years or older than 50 years
• Symptoms of atherosclerotic disease elsewhere
Clinical Findings
• Negative family history of hypertension
• Cigarette smoking or use of other tobacco products
• Renal failure with ACE inhibition. An increase in serum
creatinine of more than 15% is strongly associated with a
high incidence of RVD
• Recurrent pulmonary edema (flash edema)
• Advanced fundoscopic changes
• Systolic-diastolic abdominal bruits (In combination with
hypertension, these are suggestive of RVHT)
• Unexplained renal insufficiency in elderly patients
• Congestive heart failure with poor control of hypertension
and renal insufficiency in the absence of a significant
decrease in ejection fraction
Risk factors associated with
ischemic renal disease
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Carotid artery disease
Coronary artery disease
Diabetes mellitus
Hypertension
Obesity
Old age
Peripheral vascular disease (vascular disease in the
extremities, e.g. the legs)
• Smoking
• Familial history of AD or RAS
Differential diagnosis
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Acute renal failure
Chronic glomerulonephritis
Malignant HTN causing renal failure
Hypersensitivity nephropathy
Nephrosclerosis
Essential and other causes of hypertension with renal
insufficiency
Mortality/Morbidity
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In patients with hypertension, atherosclerotic renal artery
disease is a strong predictor of increased mortality
relative to the general population. In the setting of renal
dysfunction, RVHT is associated with the greatest
mortality rate.
Major complications of RVHT include end-organ
damage due to chronically uncontrolled hypertension
(CAD, stroke, etc.) and progressive renal insufficiency,
which is an important sequel of chronic renal ischemia.
HTN may be particularly difficult to control or may
require multiple antihypertensive agents (with increased
adverse effects and drug interactions).
In addition, atherosclerotic RVD frequently occurs in the
setting of generalized vascular disease (i.e. cerebral,
cardiac, peripheral), with the consequences associated
with disease in those vascular beds.
Work-up
Laboratory Studies:
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Serum creatinine and creatinine clearance.
24-hour urine protein: Vascular renal disease is associated with minimal-tomoderate degrees of proteinuria, which are rarely in the nephrotic range.
Urinalysis shows absence of red blood cells or red blood cell casts (a hallmark
of glomerulonephritis).
Serologic tests for SLE or vasculitis should be performed if these conditions
are suggested (e.g. antinuclear antibodies, C3, C4, antinuclear cytoplasmic
antibodies).
Measurement of plasma renin activity: The baseline plasma renin activity is
elevated in 50-80% of patients with RVHT.
Captopril test: Measuring the increase in the baseline plasma renin activity 1
hour after the administration of 25-50 mg of the ACE inhibitor (captopril) can
increase the predictive value of baseline plasma renin activity. Patients with
RAS have an exaggerated increase in baseline plasma renin activity, perhaps
due to the removal of the normal suppressive effect of high angiotensin II
levels on renin secretion in the ischemic kidney.
Renal vein renin ratio ≥ 1.5 between stenotic/contralateral kidney are of
considerable value in determining functionally important lesions and
predicting cure or improvement of HTN with PTA or surgical intervention
(although PTA or surgery will also benefit one-third to half the patients
without lateralizing renal vein renin ratios).
Imaging Studies
• Ultrasound/Duplex ultrasound: Renal US may show significant
asymmetry of kidney size (i.e. size discrepancy of >1.5 cm).
Additionally, US may be useful to determine the presence of a solitary
kidney. Duplex ultrasound scanning is a noninvasive diagnostic
technique that combines a B-mode ultrasound image with a pulse
Doppler unit to obtain flow velocity data. It is noninvasive, relatively
inexpensive, and can be used in patients with any level of renal
function.
• Captopril renography: Radionuclide renal imaging can be done using
Tc99m DTPA, Tc99m MAG3 or OIH ( orthoiodohippuran). It is a safe
and noninvasive way to evaluate renal blood flow and excretory
function. When captopril is administered (especially in unilateral
RAS), the GFR of stenotic kidney falls by about 30% and the normal
kidney exhibits an increase in the GFR. Sensitivity of this test is about
85-90% and specificity of 93-98%. Significant azotemia and bilateral
RAS adversely affect this accuracy, making it unsuitable for these
situations.
• CT angiography (Spiral CT): This technique involves the use of IV
iodinated contrast material and allows 3-dimensional reconstruction
images of the renal arteries. Spiral CT is a useful technique that avoids
arterial catheterization and produces accurate images of renal artery
anatomy.
Imaging Studies
• Magnetic resonance angiography: Magnetic resonance
angiography (MRA) is a very good noninvasive technique
capable of demonstrating the renal vascular anatomy and
direct visualization of renal artery lesions without
iodinated contrast material.
• The limitations of MRA are its expense and its
contraindication in patients with metallic clips,
pacemakers, intraocular metallic devices, or other
implants.
• The sensitivity of MRA > 90% for proximal RAS, 82% for
main RAS, and very low ( 0%) for segmental stenosis.
Dynamic gadolinium-enhanced magnetic resonance angiogram
(MRA) shows normal renal arteries.
Imaging
• Renal arteriography: This technique remains the gold standard for the
confirmation and identification of renal artery occlusion in persons
with IRD. Specialists can perform renal arteriography by conventional
aortography, intravenous subtraction angiography, intra-arterial digital
subtraction angiography (DSA), or carbon dioxide angiography.
• Conventional aortography produces excellent radiographic images of
the renal artery.
• It is, however, an invasive procedure that requires an arterial puncture,
carries the risk of cholesterol emboli, and uses a moderate amount of
contrast material with the risk of contrast-induced acute tubular
necrosis (ATN).
• Low osmolar contrast material can limit the risk of CEN.
Digital subtraction flush aortogram in a 77-year-old normotensive man
shows marked left renal artery stenosis and diffuse aortic atheroma. The
patient presented with lower-limb claudication.
• Digital subtraction flush aortogram in an 83-year-old mildly hypertensive
man shows complete occlusion of the left renal artery; only a stub of the
artery is visualized. Note the diffuse aortic atheroma. The patient presented
with lower-limb claudication.
Aortogram of a 4-year-old child with renovascular hypertension caused by
stenosis of the left renal artery.
Flush aortogram in a 32-year-old man with familial hypercholesterolemia
and difficult-to-control hypertension. Radiograph shows a complete
occlusion of the right renal artery and marked stenosis of the left renal
artery.
• Left: Flush aortogram in a 63-year-old man with hypertension shows
marked stenosis of the right renal artery and complete occlusion of the
left renal artery. Note the extensive atheroma in the aorta and iliac
arteries.
• Right: nephrogram-phase image shows a significantly smaller left
kidney with a faint nephrogram.
Selection of diagnostic tests
• Once patients are identified as being at higher risk of
RAS, the choice of the best test for diagnosis is
controversial.
• Accurate identification of patients with correctable
renovascular hypertension can be difficult with use of
standard noninvasive techniques (e.g. sonography, CT
angio, MRA) because they provide only indirect
evidence of the presence of renal artery lesions.
• On the other hand, invasive techniques with more
accurate diagnostic potential can produce a worsening
of renal function because of contrast toxicity and
complications related to the procedures themselves (e.g.
arterial puncture, catheter-induced atheroembolism).
Selection of diagnostic tests
• When the history is highly suggestive and no risk for radiocontrastmediated renal injury is present, an intraarterial DSA or
conventional angiogram is the appropriate initial test. In patients at
risk, a carbon dioxide angiogram can determine the presence of a
stenosis, and the risk of radiocontrast angiogram is imposed only
on those individuals are most likely to benefit.
• Perform a spiral CT scan, MRA, or duplex ultrasonography
(depending on availability and local experience) when moderate
suspicion of renovascular disease exists. A negative test result
indicates that an RAS is highly unlikely, while a positive test result
can be followed by renal arteriography.
Selection of Diagnostic Tests
Gilfeather et al performed a study evaluating conventional
angiography versus gadolinium-enhanced MRA in 54
patients and 107 kidneys. The study showed that in 70
kidneys (65%), the average degree of stenosis reported
by readers of both modalities differed by 10% or less.
In 22 cases (21%), MRA overestimated the degree of
stenosis by more than 10% relative to the results of
conventional angiography; in 15 cases (14%), MRA
underestimated the stenosis by more than 10%.
Selection of Diagnostic Tests
• The obvious advantages of conventional angiography
are its ability to accurately determine the extent of the
lesion and suggesting its clinical importance (by
demonstrating post-stenotic dilation) and the ability to
concurrently perform endovascular therapy.
• However, specialists should weigh these advantages
against the higher cost and greater morbidity of
conventional angiography.
• All these tests should be done if the pt is a reasonable
candidate for revascularization procedure.
Prognosis
• Images from sequential abdominal aortographs or duplex ultrasound
scans in patients with documented renal artery lesions who have been
treated medically have shown that progressive arterial obstruction
occurs in 42-53% of patients with atherosclerotic RAS, often within
the first 2 years of radiographic follow-up.
• The incidence rate of progression to complete renal artery occlusion in
these studies ranges from 9-16%; this often occurs in patients with a
high-degree stenosis. In a study of 85 patients at the Cleveland Clinic
who were followed for 3-172 months, patients with mild-to-moderate
stenosis remained unchanged upon follow-up, and 39% of patients
with greater than 75% lesions progressed to total occlusion.
• The prognosis of patients with RVHT is difficult to ascertain and varies
with the extent of the occlusive phenomena, the sensitivity of the
individual to antihypertensive therapy, and the efficacy of surgical
repair and/or angioplasty.
• RVHT in the setting of chronic renal ischemia and consequent renal
dysfunction has been linked to worse outcomes.
Treatment
• It is crucial to remember that not all HTN in
the presence of anatomic RAS is
renovascular HTN.
• Many normotensive patients and those with
essential HTN can also have some degree of
RAS and do not need revascularization.
Treatment
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Interventions appropriate for patients with
RAS/RVHT may include
Medical therapy
Percutaneous transluminal angioplasty (PTA) with
or without vascular stent placement
Surgical revascularization
Intravascular ultrasonography-guided atherectomy
Medical therapy
• Treatment with antihypertensive drugs is indicated and
optimal blood pressure control is essential. ACE inhibitors
should be avoided. CCB, beta blockers and many other
classes of drugs can be safely used. In many patients, blood
pressure can be well controlled with medical therapy.
• Other risk factors that should be addressed include
atherosclerosis, smoking, and hyperlipidemia.
• Definitive therapy for the RAS should always be considered
not only for better control of HTN but also to prevent the
development of ischemic nephropathy.
• In patients with diffuse atherosclerosis, the complication
rate with both surgery and angioplasty is relatively high.
Medical therapy may be preferred to other treatments many
cases after carefully weighing risks and benefits of the
invasive intervention.
Percutaneous transluminal
angioplasty (PTA)
• PTA has become the procedure of choice for treatment of
symptomatic stenoses. Patency rates after PTA are strongly
dependent on the size of the vessel treated and the quality
of inflow and outflow through the vessel. Because of the
excellent results obtained with renal angioplasty, it is the
most commonly performed procedure in symptomatic
RAS.
• Previously, a solitary or transplanted kidney was
considered a contraindication for PTA. This is no longer
the case and, angioplasty is now considered the procedure
of choice for treatment of RAS in these patients.
PTA
• Technical success is achieved in more than 90% of
patients, and patency rates are 90-95% at 2 years for FMD
and 80-85% for atherosclerosis.
• Restenosis requiring repeat angioplasty has been reported
in fewer than 10% of patients with FMD and in 8-30%
with atherosclerotic stenosis.
• Improvement in blood pressure control with fewer
antihypertensive medications is achieved in 30-35% of
fibromuscular lesions and in 50-60% of atherosclerotic
lesions.
• A success rate of 83% has been reported with PTA in RAS
associated with renal transplantation.
Left: A balloon angioplasty catheter is seen in situ across the left renal
artery stenosis.
Right: After angioplasty, an excellent anatomic (and functional) result was
achieved.
Left renal artery stenosis
After PTA
Vascular stent placement
• Vascular stenting is considered complementary to PTA.
• Many vascular stents are now available, which can be
either self-expanding or balloon expandable. Drug-eluting
stents are also available.
• Intravascular stents placed during angioplasty may be
helpful in the prevention of restenosis.
• Early results suggest that stenting may prove useful in
patients with ostial disease, in those in whom restenosis
occurs after PTA, or in those with complications (e.g. renal
artery dissection) resulting from PTA.
• Primary renal artery stenting in patients with
atherosclerotic RAS has a high technical success rate and a
low complication rate.
Intravascular ultrasonographyguided atherectomy
• In a single reported case, hypertension
secondary to AD was successfully
diagnosed with intravascular sonography,
and intravascular sonography-guided renal
atherectomy was curative.
Surgical revascularization
• Currently, surgical revascularization is reserved
for patients in whom the main renal artery appears
completely occluded and in whom the surviving
renal parenchyma is vascularized by collaterals.
• Surgical revascularization might also be used
when an ostial stenosis is present with a
buttressing atheroma on either side of the ostium.
Surgery
• Several surgical options are available.
• The stenotic segment may be excised and the artery resutured directly
onto either the aorta or surviving stump.
• A vein graft may be transplanted or the kidney resected and
reimplanted in the iliac fossa with the renal artery anastomosed to the
iliac artery.
• Another novel method involves a splenectomy and anastomoses of the
splenic artery to the renal artery when RAS involves the left kidney.
The underlying diagnosis determines the results of this surgery.
• With advanced diffuse atherosclerosis, surgery may become less
feasible because the certainty that the RAS is the cause of the
hypertension is less and the prognosis may be determined by
comorbidities.
Surgery
• A potential complication of surgery is the release of
cholesterol emboli during the surgery which can cause
renal failure; however, 80-90% of patients undergoing
operation for atherosclerotic RAS benefit with cure or
improvement. The perioperative mortality rate is less than
5%.
• In patients with FMD, the cure rate is as high as 80%, and
morbidity rates are low. However, these results are not
significantly better than what can be achieved with renal
angioplasty, at less morbidity, mortality, cost, and
inconvenience.
• In patients with diffuse atherosclerosis, the complication
rate with both surgery and angioplasty is relatively high.
Criteria for Revascularization
• All patients with bilateral stenosis and
stenosis in a solitary functioning kidney are
candidates for revascularization, regardless
of whether they have renal insufficiency.
• When renal insufficiency is present, patients
with unilateral stenosis are also possible
candidates for revascularization
Criteria for Revascularization
• When renal function is normal or nearly normal, specialists
recommend revascularization if the patient meets the following
criteria:
– The degree of stenosis is more than 80-85%.
– The degree of stenosis is 50-80%, and captopril-enhanced scintigraphy
findings demonstrate an activation of intrarenal renin angiotensin system.
• Conversely, physicians can choose observation instead of
revascularization (serial imaging every 6 mo with duplex scanning,
accurate correction of dyslipidemia, use of drugs that block platelet
aggregation) when the patient meets the following criteria:
– Stenosis is 50-80%, and scintigraphy findings are negative.
– The degree of stenosis is less than 50%.
Criteria for Revascularization
• When renal insufficiency is present and the objective is
recovery of renal function together with prevention of
further renal function impairment, the prerequisites for
revascularization are as follows:
– The serum creatinine level is lower than 4 mg/dL.
– The serum creatinine level is higher than 4 mg/dL but with a
possible recent renal artery thrombosis.
– When these conditions are satisfied, revascularization can be done
if the following apply:
• The degree of stenosis is more than 80%.
• The serum creatinine level is increased after administration of ACE
inhibitors.
• The degree of stenosis is 50-80%, and the scintigraphy findings are
positive.
When to chose conservative therapy
• Restrict conservative treatment in patients with an
established diagnosis of IRD only to those with absolute
contraindications to surgery or angioplasty or to patients
who are likely to succumb due to other comorbid
conditions before advancing to end-stage renal disease
because of IRD.
• In these cases, the clinicians have to rely on pharmacologic
agents (e.g. combination of calcium channels blockers to
control blood pressure and optimize renal perfusion),
accepting the high probability of deterioration in renal
function.