Brian M. Benway, MD
Gerald L. Andriole, MD, FACS
BASICS
DESCRIPTION
• Renal artery stenosis (RAS) refers to anatomic vascular lesion that causes decreased blood flow to the kidney
• May not be associated with hypertension (HTN)
• May be atherosclerotic in nature (athersclerotic renal artery stenosis or ARAS)
• Rarely caused by fibromuscular dysplasia (FMD)
• Renovascular HTN (RVH) refers to HTN that is caused by renal hypoperfusion and is reversed by correction of the lesion or nephrectomy
EPIDEMIOLOGY
Incidence
• RAS often found incidentally
– 33% of patients with aorto-occlusive disease
– 20% of patients with coronary artery disease (CAD)
– 43% of patients with diabetes
– 7% of asymptomatic normotensive adults >65 yr (1)
Prevalence
RVH <1% of hypertensive patients
RISK FACTORS
• Atherosclerosis
• Diabetes
• CAD
• Advanced age
Genetics
N/A
PATHOPHYSIOLOGY
• Atherosclerosis
– Accounts for 70% of all RAS
– Nearly half of patients will have progressive obstruction within 2 yr of diagnosis
– Usually located at the ostium or proximal renal artery
– 10% caused by FMD, which causes primarily distal lesions
• RVH
– Results from significant vascular stenosis which produces renal hypoperfusion
– Hypoperfusion results in increased renin levels, which in turn increases angiotensin II levels
– Angiotensin elevates blood pressure through several mechanisms
Generalized vasoconstriction
Increased aldosterone production, promoting sodium absorption and excretion of potassium and hydrogen
Causes efferent arteriolar vasoconstriction to maintain glomerular filtration
• FMD is a nonatherosclerotic, noninflammatory process of the renal vessels
– Intimal fibroplasia occurs in children and young adults
Accounts for 10% of FMD
Can be associated with dissection and hematoma
Involves proximal or midportion of artery, appears smooth on angiography
Invariably progressive if untreated
– Medial fibroplasia
70–80% of FMD
More common in women aged 25–50
Usually bilateral
“String of beads” appearance on angiography
Rarely associated with functional loss and may be managed medically
– Perimedial fibroplasia
Women aged 15–30
Dense collar of collagen constricting the artery
Length is variable
Frequently associated with development of collaterals
Invariably progressive if not treated
– Fibromuscular hyperplasia
Extremely rare (2–3% of all renal artery lesions)
Most commonly affects children and young adults
Progressive if untreated
ASSOCIATED CONDITIONS
• High-grade retinopathy
• Atherosclerosis
• Diabetes
• CAD
• Peripheral vascular disease
GENERAL PREVENTION
Reduction of risk factors for cardiovascular disease and diabetes
DIAGNOSIS
HISTORY
• Onset of HTN after age 50
• No family history of HTN
• Difficult-to-control HTN, on multiple antihypertensives
• Increase in serum creatinine with use of ACE inhibitors or angiotensin receptor blockers (ARBs)
PHYSICAL EXAM
• Blood pressure measurement
• Abdominal exam with auscultation for bruit
• Retinal exam
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Plasma renin activity (PRA)
– By itself, not diagnostic of RAS or RVH
• Captopril test
– Useful for excluding RVH
– Diuretics and ACE inhibitors stopped 1 wk prior
– PRA measured before and 1 hr after 25-mg dose of captopril
– Positive test if postdose PRA >12 ng/mL/h, absolute increase of PRA >10 ng/mL/h, 4-fold increase in PRA over baseline
– Not appropriate in children or in patients with azotemia
Imaging
• Arteriography is gold standard
– Highly sensitive and specific (99%)
– Provides detailed anatomy, and allows for discrimination between FMD subtypes
– Allows for simultaneous endovascular treatment
– Invasive
– Recommended as initial diagnostic intervention in patients with high suspicion for RVH
• Captopril renography
– Keep well hydrated on a liberal salt diet
– Off ACE inhibitors for 3–5 days prior to exam
– 99mTechnetium-MAG3 renal scan generally used before and 1 hr after captopril dose
– Diagnostic criteria for RVH: Delay in maximal activity >11 min, asymmetrical peak activity, cortical retention of radionuclide, significant decrease in glomerular filtration rate
– Recommended as initial diagnostic intervention in patients with low-to-moderate suspicion for RVH
• Duplex ultrasonography
– Positive diagnostic criteria: Peak systolic velocity of renal artery >80 cm/s, ratio of diameter of renal artery to aorta >3.5
– Inexpensive, noninvasive, but quality of study is operator dependent
• Magnetic resonance angiography (MRA)
– May be more sensitive than ultrasound or renography, but inferior to conventional arteriography
– Poorly visualizes distal arteries
– Contraindicated in patients with met al or claustrophobia
– Contrast must be used with caution in patients with renal insufficiency (2)
• Computed tomography angiography (CTA)
– Uses potentially nephrotoxic contrast agents
– More widely available and cost-effective compared to MRA
Diagnostic Procedures/Surgery
• Renal angiography
• Renal vein renin sampling
– Useful in determining which kidney is primary contributor to RVH in patients with bilateral lesions
Pathologic Findings
• Renal biopsy indicated in patients with creatinine >4 mg/dL
– Tubular atrophy, interstitial fibrosis, arteriosclerosis indicate functional recovery may be possible
– Widespread glomerular hyalinization indicates irreversible injury
DIFFERENTIAL DIAGNOSIS
• Aortic aneurysm
• Essential HTN
• Functional adrenal adenoma
• Intrinsic renal disease
• Renal artery aneurysm
TREATMENT
GENERAL MEASURES
• Recognition of underlying cause is critical in guiding management
• Smoking cessation
• Weight loss
• Reduction of risk factors for cardiovascular disease and diabetes
MEDICATION
First Line
• ACE inhibitors/ARBs: Improves HTN in 96% of patients with RVH. May not prevent progression of atherosclerotic lesions.
– Captopril: 25–50 mg PO BID-TID
– Enalapril: 10–40 mg PO QD
– Losartan: 25–100 mg PO divided QD-BID
– Telmisartan: 20–80 mg PO QD
• Aspirin 81 mg PO QD
• Statins
Second Line
• Thiazide diuretics
• Loop diuretics
• Calcium channel blockers
• β-blockers
SURGERY/OTHER PROCEDURES
• Surgical intervention recommended for patients with high-grade stenosis, bilateral disease, solitary kidney, declining renal function, pulmonary edema, congestive heart failure (3)
• Angioplasty with or without endovascular stenting
– Percutaneous access through common femoral artery
– Selective angiography performed
– ≥70% stenosis treated with angioplasty and deployment of balloon-mounted stent
– Angioplasty without stenting is associated with increased risk of restenosis
• One recent clinical trial suggests that the addition of renal artery stenting to comprehensive, multifactorial medical therapy did not confer a significant benefit (4)
• Aortorenal bypass (hypogastric or saphenous vein)
• Nephrectomy (especially in patients with a poorly functioning ipsilateral renal unit)
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Treatment of concomitant disease
– Antiplatelet agents
– Statins
– Smoking cessation
– Weight loss
Complementary & Alternative Therapies
Sympathetic renal denervation using radiofrequency ablation is investigational at the present time, but shows promise (5)
ONGOING CARE
PROGNOSIS
Untreated disease, except for medial fibroplasia, is often progressive and can result in renal functional loss
COMPLICATIONS
• Functional loss, worsening HTN, pulmonary edema, congestive heart failure in untreated patients
• Endovascular interventions: Access site hematoma, renal artery dissection, thrombosis, contrast-induced nephropathy
• Surgical interventions: Hemorrhage, wound infection, hematoma, anesthesia complications
FOLLOW-UP
Patient Monitoring
High-risk patients and those on medical therapy should be observed with serial metabolic and renal function studies in addition to Doppler ultrasonography
Patient Resources
http://www.nlm.nih.gov/medlineplus/ency/article/000204.htm
REFERENCES
1. Hansen KJ, Edwards MS, Craven TE, et al. Prevalence of renovascular disease in the elderly: A population-based study. J Vasc Surg. 2002;36:443–451.
2. Grobner T. Gadolinium–a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant. 2006;21:1104–1108.
3. Novick AC. Options for therapy of ischemic nephropathy: Role of angioplasty and surgery. Semin Nephrol. 1996;16:53–60.
4. Cooper CJ, Murphy TP, Cutlip DE, et al. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med. 2014;370(1):13–22.
5. Krum H, Schlaich M, Whitbourn R, et al. Catheter-based renal sympathetic denervation for resistant hypertension: A multicentre safety and proof-of-principle cohort study. Lancet. 2009;373:1275–1281.
ADDITIONAL READING
• O’Neill WC, Bardelli M, Yevzlin AS. Imaging for renovascular disease. Semin Nephrol. 2011;31:272–282.
• Piecha G, Wiecek A, Januszewicz A. Epidemiology and optimal management in patients with renal artery stenosis. J Nephrol. 2012;25:872–878.
• Safian RD, Textor SC. Renal-artery stenosis. N Engl J Med. 2001;344:431–442.
See Also (Topic, Algorithm, Media)
• HTN, Urologic Considerations
• Renal Artery Aneurysm
• Renal Artery FMD
• Renin, Plasma and Renal Vein
• Renal Artery Stenosis Images 
CODES
ICD9
• 250.40 Diabetes with renal manifestations, type II or unspecified type, not stated as uncontrolled
• 405.91 Unspecified renovascular hypertension
• 440.1 Atherosclerosis of renal artery
ICD10
• E11.21 Type 2 diabetes mellitus with diabetic nephropathy
• I15.0 Renovascular hypertension
• I70.1 Atherosclerosis of renal artery
CLINICAL/SURGICAL PEARLS
• RVH HTN is caused by significant stenosis of the renal artery and is reversed by correction of stenosis or nephrectomy.
• Renal angiography remains gold standard for diagnosis.
• With the exception of medial fibroplasia, untreated RVH disease often leads to progressive renal functional loss.