Renal Artery Stenosis

November 12, 2009

Lance D. Dworkin, M.D., and Christopher J. Cooper, M.D.

Clinical Practice

2010 년 3 월 23 일 화요일

신장내과 R4 이완수

Case Vignette• Age/Sex

– 73/male

• Chief compliant– shortness of breath

ER visit

• Personal History– former smoker

• Past History– Hypertension– Dyslipidemia

• Vital sign BP 160/75 mmHg HR 60 beats/min RR 24 breaths/min

• Physical Examination Chest auscultation - diffuse rales Pitting edema (1+)

• Lab. Serum Creatinine 1.4 mg/dL (eGFR 52ml/min) Urinalysis protein 1+

Case Vignette• Condition improves after treatment (IV diuretics)• But, systolic BP remains elevated (170 mmHg)

• Magnetic resonance angiography (MRA) – diseased aorta– Lt. renal artery (ostial lesion) High grade “atherosclerotic stenosis”– Rt. renal artery normal

• How should he be further evaluated and treated?

Renal artery stenosis (Lt.)

Outline• The Clinical Problem• Strategies and Evidence

– Evaluation– Treatment Options

• Medical Therapy• Surgical Therapy• Angioplasty and Stenting

• Areas of Uncertainty• Guidelines• Conclusions and Recommendations

The Clinical Problem• “Renal-artery stenosis”• Definition

– narrowing of one or both renal arteries or their branches.• Cause

– 1. atherosclerosis (most common, 90%)– 2. fibromuscular dysplasia (Less frequently)– 3. other causes (rare)

• Vasculitis (Takayasu’s arteritis)• Dissection of the renal artery• Thromboembolic disease • Renal artery aneurysm • Renal artery coarctation • Extrinsic compression • Radiation injury

• Characteristics of Atherosclerotic Renal-Artery Stenosis and Fibromuscular Dyspla-sia

balloon angio-plasty

controver-sial

Effective Tx.?

• Prevalence– atherosclerotic renal artery stenosis in CKD – 0.5~5.5%– true frequency maybe higher

(∵ often asymptomatic)

• Anatomical progression– occur in more than one third of patients– But, one study

• 5 yrs F/U, “Stenosis” “Occlusion “• only 3~15% patients treated medically• conducted before statin therapy was available

Medical treatment is impor-tant!!

• Pathogenesis

RAS : renal artery steno-sisRBF : renal blood flow

• Other vascular event?– Renal-artery stenosis ( HTN, CKD) increased risk for vascular events

– Explanation?? Uncertain• concomitant atherosclerosis in other vascular beds• activation of the renin–angiotensin–aldosterone• activation of the sympathetic nervous systems• associated renal insufficiency• all these factors

chronic kidney disease (25%, vs 2%)coronary artery disease (67% vs 25%)stroke (37% vs 12%)peripheral vascular disease (56% vs 13%)

• Classic clinical clues (renal artery stenosis)

1. onset of stage 2 hypertension (BP >160/100mmHg) after 50yrs old2. family history of hypertension (-)3. hypertension associated with renal insufficiency (Esp, RAAS inhibition agent renal fuction wosens)4. hypertension with repeated hospital admissions heart failure drug-resistant hypertension (treatment c three drug of different class BP control fail)

Strategies and Evidence

Diagnostic Imaging Tests for Renal-Artery Stenosis

• Once renal-artery stenosis is suspected??• confirmation of the diagnosis?? imaging!! ∵ biochemical tests (plasma renin concentrations) speci-

ficity ↓

Duplex Ultrasonography in a Patient with Renal-Artery Stenosis

• Excellent tool

non-invasive no apparent side effects

• Measurement “renal-artery velocity” functional assessment of the “severity of stenosis” higher velocity greater pressure differential across the stenosis

• Limitation abdominal obesity bowel gas technically demanding (not available at all centers)

Magnetic Resonance AngiographyComputed Tomographic Angiography

• High-resolution multislice detector devices• Elegant images of the renal arteries and the abdominal aorta• Limitation may affect image quality

– equipment– technique– reconstruction of the images– patient-related factors

• presence of calcium• presence of stents• ability to hold one's breath during imaging

• Caution)– CKD patients : toxicity of the contrast medium

• nephrogenic systemic fibrosis is associated with gadolinium

• nephropathy is associated with iodinated contrast dye

• Rt. renal aterty (arrow) 70% ostial stenosis systolic pressure gradient of 28mmHg

• Lt. renal artery (arrowhead) 40% ostial stenosis pressure gradient of 13mmHg

Magnetic Resonance Angiography of the Renal Arteries Showing Severe Bilateral Stenosis

Digital subtraction angiography

• Best image quality, anatomy information• use of small-diameter catheters and minimal

amounts of contrast material reduce the risk of vascular complications and

contrast nephropathy• Limitation

– invasive– only in experienced centers– contrast nephropathy in CKD– atheroembolic event– vascular complication at punture site– Radation exposure

• degree of atherosclerosis of the aorta• size of the kidney• extent of poststenotic dilatation• rapidity of the appearance and washout of contrast mate-rial Useful in diagnosis of Renal artery

stenosis“Functional significance” of the lesion ?Predict the “response to revascularza-tion” ? No conclusive test

• nuclear scintigraphy• renin sampling from the renal veins• pressure gradients across stenoses

Kidney (supplied by an occluded renal artey) is viable?Contributing to hypertension ? Stenosis is affecting intrarenal pressure?

Treatment Options• Medical Therapy• Surgical Therapy• Angioplasty and Stenting

improved survival improved BP control less impairment of renal function

Medical Therapy• Cornerstone of treatment for renal-artery stenosis• Recommendations

– Multidrug regimens for BP control– RAAS inhibitor is recommended in most patients (Renin–angiotensin–aldosterone system is often activated in

patients with renal-artery stenosis)– alpha-blocker or beta-blocker– long-acting CCB– diuretics

• Caution) “Bilateral severe stenosis“ Use of “RAAS inhibitor” ARF

High-grade stenosis in one kidneyAdvanced chronic kidney disease probability of this complication appears to be low in most cases, it is reversible with the discontinuation of treat-ment

Medical Therapy• Recent data

– ACE inhibitor reduced risk of death– Statin reduction in the severity of renal

artery stenosis– Statin c stenting improve survival – Statin, antiplatelet therapy benefit in pa-

tient with atherosclerotic disease

Surgical Therapy• Surgical revascularization

– durable relief of renal-artery stenosis– improves BP control and kidney function

• Safety– recent data have indicated a 10% in-hospital mortality after this pro-

cedure among Medicare patients

• “balloon angioplasty” vs “surgery”– 58 patients with renal-artery stenosis, randomized trial– resulted in similar rates of cure or improvement in HTN, renal func-

tion

“nonsurgical revascularization” first-line approach (if an intervention is planned)

Angioplasty and Stenting• “Fibromuscular dysplasia”

– balloon angioplasty remains the preferred form many patients are able to discontinue all antihyperten-

sive medications– But, medical therapy alone may be appropriate in pa-

tients with well-controlled hypertension

• “Atherosclerotic renal artery stenosis”– balloon angioplasty

• Less effective• Restenosis 71%↑• 3 multicenter trials, without stenting

– 1 yr follow-up, no significant improvement in BP

• But, controversial

Angioplasty and Stenting• Predictors of a favorable outcome of angio-

plasty– 40 years ↓ at diagnosis– duration of hypertension <5 yrs– systolic BP <160 mmHg

Angioplasty and Stenting• Stents

– limit elastic recoil– restenosis-free patency ↑

(compared with angioplasty alone)– BP control ↑after stenting

Angioplasty and Stenting• Recent trials

– 1. comparing stenting plus medical therapy with medical therapy alone

• preservation of renal function• no significant benefits with the addition of stenting

– 2. Angioplasty and Stenting for Renal Artery Lesions (ASTRAL)

• stent revascularization in addition to medical ther-apy vs medical therapy alone

• renal function, mean systolic blood pressure, in rates of renal or cardiovascular events or death

• no significant difference between the study groups at the 5yrs follow-up

Angioplasty and Stenting– 3. Stenting in Renal Dysfunction Caused by Atheroscle-

rotic Renal Artery (STAR) trial• prevention of loss of kidney function• serious procedure-related complications• stenting plus medical therapy vs medical ther-

apy alone • did not show a benefit

Angioplasty and Stenting• Revascularization

– renin–angiotensin–aldosterone system ↓ – sympathetic nervous system ↓– possible cardiovascular benefits

“pharmacologic therapy”?? directed at these pathwaysmay have similar benefits

improved survival improved BP control less impairment of renal function

Areas of UncertaintyResponse to revascularization? no method reliably predicts

Optimal treatment strategy?“Angioplasty and Stenting” vs “medical therapy alone” remains unclear

• Data are lacking– randomized clinical trials comparing the effects of various medical reg-

imens

• Available data from randomized trials– not shown a benefit of “revascularization plus medical therapy” with

respect to blood-pressure control and renal function – But, these trials had methodologic limitations, were not powered for the

assessment of cardiovascular outcomes, and did not include quality-of-life assessments

Previous algo-rithm

• Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study – large, multicenter, randomized, controlled trial – funded by the National Institutes of Health– scheduled to be completed in 2011 – medical therapy plus stent revascularization vs

medical therapy alone – end point : cardiovascular and renal events – Pending the results of the study

• best treatment for renal-artery stenosis ?• whether to evaluate ? remain uncertain

Guidelines• American College of Cardiology–American Heart Association 2005

guidelines (for the care of patients with peripheral-artery disease, including renal-

artery stenosis)

• Revascularization recommendations – class I evidence (i.e., general agreement on usefulness)

• recurrent congestive heart failure• pulmonary edema

– class IIa evidence (i.e., conflicting opinions, but with the preponderance of evidence favoring usefulness)

• global renal ischemia• progressive chronic kidney disease• unstable angina• hypertension that is worsening• resistant to medical therapy• malignant• unexplained unilateral small kidney• cannot tolerate antihypertensive medication

Conclusions and Recommenda-tions

• A diagnosis of renal-artery stenosis should be considered in any pa-tient with a history of severe or resistant hypertension, hypertension that is associated with renal insufficiency, or disease in other vas-cular beds.

Clinical Finding Associated with Renal Artery StenosisHypertension Abrupt onset of hypertension (age<40) fibromuscular dysplasia Abrupt onset of hypertension (age>50) renal artery stenosis Accelerated or malignant hypertension Refractory hypertension (not responsive to therapy c 3≥drugs)Renal abnormalities Unexplained azotemia renal artery stenosis Azotemia induced by treatment with an angiotensin converting enzyme inhibitor Unilateral small kidney Unexplained hypokalemiaOther findings Abdominal bruit, flank bruit, or both Severe retinopathy Carotid, coronary, or peripheral vascular disease Unexplained congestive heart failure or acute pulmonary edema

Conclusions and Recommenda-tions

• Initial examination measurement of kidney function and a lipid profile

• Anatomical diagnosis– duplex ultrasonography– CTA or MRA (if high-quality duplex imaging is not available)

• Therapy – intensive medical therapy– tight BP control with a blocker of the RAAS (serum creatinine and potassium should be closely monitored)– administration of an antiplatelet agent and a statin– Treatment of diabetes and chronic kidney disease

• Revascularization in the treatment of atherosclerotic renal-artery stenosis ? controversial