Renal Artery Disease Renal Artery Disease Renal Artery Disease ...

Renal Artery Disease Renal Artery Disease Renal Artery Disease ...


RC 312

Renal Artery Disease

Renal Artery Disease

Myron Pozniak MD

University of Wisconsin, Madison

W. Dennis Foley, MD

Medical College of Wisconsin, Milwaukee

Prof. Dr. med. Stefan Schönberg

Universitätsklinikum Mannheim, Germany

Renal Artery Disease

Myron Pozniak MD

University of Wisconsin, Madison

Clinical Concerns




Renal Artery Disease

W. Dennis Foley, MD

Medical College of Wisconsin, Milwaukee

CT Techniques and Interpretation

Renal Artery Disease

Prof. Dr. med. Stefan Schönberg

Universitätsklinikum Mannheim, Germany

MR Techniques and Interpretation

Renal Artery Disease

Clinical Concerns





Literature Review

Over 5,000 articles per year deal with HTN

• Surgery

• Cardiology

• Nephrology

• Radiology

20 million Americans have some degree

of Chronic Kidney Disease (CKD)

• > 80% of patients with CKD have

hypertension (HTN)

Renal Artery Disease is a component of (CKD)

• But how should we identify & treat HTN?

• Vascular intervention

• Medically

Treatment of hypertension in chronic kidney disease. Toto RD, et al. Semin Nephrol. 2005 Nov;25(6):435-9.

Renal Artery Disease

• Atherosclerosis

• Stenosis / Thromboembolism

• Arterial dissection

• Takayasu arteritis

• Polyarteritis nodosa

• Fibromuscular dysplasia (FMD)

Renal Artery Disease

• Atherosclerosis

• Stenosis / Thromboembolism

• Arterial dissection

• Takayasu arteritis

• Polyarteritis nodosa

• Fibromuscular dysplasia (FMD)

Arterial dissection

• Traumatic

• Non - Traumatic

• Rare

• Usually associated with

Fibromuscular dysplasia & HTN

Isolated renal artery dissection, presentation, evaluation, management, and pathology. Edwards BS,

et al Mayo Clin Proc. 1982 Sep;57(9):564-71

Arterial dissection

• Presenting signs and symptoms

• Hypertension - 95%

•Recent onset - 75%

• Flank pain - 40%

• Gross hematuria - 20%

• Headaches - 25%

Isolated renal artery dissection, presentation, evaluation, management, and pathology. Edwards BS,

et al Mayo Clin Proc. 1982 Sep;57(9):564-71



Post-traumatic dissection

Takayasu arteritis

• Rare

• Affects mainly women (80%)

• From Japan, South East Asia, India, and


• Median age at discovery - 25 years

Takayasu arteritis

• Systemic, large vessel vasculitis

• Autoimmune and genetic etiology

• Chronic cell-mediated inflammatory disease

• Circumferential thickening of intima & media

• Stenoses, occlusions, or aneurysmal changes

of the aorta and its main branches

Takayasu arteritis

• Half of those patients treated with steroids

will respond

… if not add:

• Methotrexate

• Mycophenolate

Polyarteritis Nodosa

• Systemic disease

• Characterized by widespread inflammation

of small and medium-sized arteries.

Fibromuscular Dysplasia (FMD)

• Most common in young adults.

• FMD suggested by:

• HTN of abrupt onset

• Worsening HTN

• HTN increasingly difficult to treat



Fibromuscular Dysplasia (FMD)

Fibromuscular Dysplasia (FMD)

• Non-inflammatory & non-atherosclerotic

Etiology is unknown

• Young women ( 20 - 40 )

• Multifocal stenoses with a 'string-of-beads'


Fibromuscular Dysplasia (FMD)

• Management

• Antihypertensive therapy

• Percutaneous angioplasty and stenting ti of

severe stenoses

• Reconstructive surgery with complex

FMD that extends to segmental arteries

Fibromuscular dysplasia Plouin PF, et al. Orphanet J Rare Dis. 2007 Jun 7;2:28.

Renal Artery Disease

• Atherosclerosis

• Stenosis / Thromboembolism

• Arterial dissection

• Takayasu aortitis

• Polyarteritis nodosa

• Fibromuscular dysplasia (FMD)


• Accounts for 70% of renal vascular HTN.

• Until recently, most cases discovered at

angiographic workup for abdominal aortic

aneurysm or iliac occlusive disease.

• Then discovered and treated during coronary


procedures by cardiologists.

• Now most are discovered with imaging.

Imaging of Renal Vascular

Hypertension (RVHT)



Renal-artery Stenosis

• Poststenotic drop in blood pressure

• Intrarenal ischemia

• Renin release into the circulation

Development of Renal Vascular

Hypertension (RVHT)

• Renin-angiotensin-aldosterone activation

• Causing severe systemic vasoconstriction

• Sodium and water retention

WHO lists high blood pressure as the first

cause of death worldwide

• Arterial hypertension affects about 30 percent

of the people in industrialized countries

• Stroke is the most important ‘hypertension

related’ complication

Blood Pressure Reduction Is Of

Paramount Importance

• ACTION trial

• A blood pressure reduction of 15/8 mmHg

was associated itdwith a 38% reduction in

the incidence of hospitalized heart failure

Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJ, Comparative Risk Assessment Collaborating Group. Selected major risk

factors and global and regional burden of disease. Lancet (2002) 360:1347–1360.

Blood Pressure Reduction Is Of

Paramount Importance

• FEVER study

• Hypertensive patients randomized to active

treatment, t t who achieved dblood pressure

values of 138/82 mmHg, had a 28%

reduction in stroke, coronary events, and

cardiovascular mortality as compared with

those randomized to placebo, who remained

at values of 141/83 mmHg.

The Surgical Viewpoint

• In 1937, Butler reported that

nephrectomy reversed hypertension in

some patients with unilateral l renal

disease, including renal-artery stenosis.

Butler AM. Chronic pyelonephritis and arterial hypertension. J Clin Invest 1937;16:889-897.



Renal revascularization for HTN first performed

by Wylie in 1952.

• DeBakey reported the first successful series of

renal artery bypass grafts, 8 patients, 1962.

• Cooperative study of renal vascular HTN

reported in 1975. A periopertive mortality rate of

22.5% for patients undergoing renal


• Justification for aggressive surgical

approach founded on a report by Schreiber.

• Demonstrated progression of disease in

44% of vessels

• Stenoses greater than 75% went on to

occlude 39% of the time

Schreiber, M. et al. Natural history of Atherosclerosic and fibrous renal artery disease.

Urology Clinics of North America 1984. vl 11 pg 383.

As recently as 1999…

• 687 renal artery reconstructions in 568 pts.

• 3 year patency rate 97%.

• No statement as to resolution of renal HTN.

Darling, C. et al. Annuals of Surgery 1999 230 (4). (Albany Medical College)

The Cardiologist’s viewpoint

• Percutaneous stent-supported angioplasty is a

treatment option for atherosclerotic ostial renal

artery stenosis.

• Stent-supported angioplasty for severe ostial

renal artery stenosis improves renal function

and blood pressure in a broader spectrum of

patients than previously thought.

Predictors of improved renal function after percutaneous stent-supported angioplasty of severe

atherosclerotic ostial renal artery stenosis. Zeller T, et al, Circulation. 2003 Nov 4;108(18):2244-9.

The Cardiologist’s viewpoint

• Virtually hundreds of such studies

• Only a few very small ones randomized to

evaluate results against medical management

alone. (3 studies with 210 patients total)

Results inconclusive.

• … until 2 weeks ago.

The Nephrologist’s viewpoint

• “The results of renal revascularization have

been documented mainly in retrospective,

uncontrolled reports in which blood pressure

improvement was overestimated due to the

placebo effect and optimization of drug

treatment, the latter being frequently required

despite adequate revascularization.”

Non-surgical treatments of renal artery stenoses; Pluoin PF, et al, Presse Med. 1996

Apr 27;25(15):725-30



• “Middle age patients with easily

controlled hypertension and elderly

hypertensives rarely have a blood

pressure response to invasive treatment

of renal artery disease”


• Screen for RAD only recommended if

renal function is deteriorating.

Helin, K. et al. Predicting the outcome of invasive treatment of renal artery

disease. Journal of Internal Medicine. 2000, 247(1) pg 105. (Helsinki, Finland)

112 patients with renal artery stenosis on MRA.

• Only 9% underwent stenting

• 96% treated with statin

• 63% antiplatelet therapy

• 24% on ACE inhibitors

• Findings:

• Rate of progression of renal failure very slow.

• Adequate blood pressure control achieved medically

without a significant intervention rate.

Siddiqui S. et al. Outcomes of Atherosclerotic renal artery

disease in low intervention unit. Kidney International Society

Abstracts, 2004.

Let’s Look At What Imaging Can Do…

Imaging can certainly identify stenosis.

• But what should be done with this


A large controlled study was needed.

The few randomized trials comparing

revascularization with medical therapy are too

small to serve as the basis for making a

meaningful choice between the two treatments.

ASTRAL trial

• Angioplasty and STent for Renal Artery


• Birmingham Clinical Trials Unit

University of Birmingham

Birmingham, UK.



Revascularization versus Medical Therapy

for Renal-Artery Stenosis

The ASTRAL Investigators

Keith Wheatley, D.Phil., Natalie Ives, M.Sc., and Richard Gray, M.A., M.Sc., University of Birmingham, Birmingham;

Philip A. Kalra, F.R.C.P., M.D., Salford Royal Hospital, Salford; Jonathan G. Moss, F.R.C.R., F.R.C.S., North

Glasgow University Hospitals, Glasgow; Colin Baigent, B.M., B.Ch., Clinical Trial Service Unit, Oxford; Susan

Carr, F.R.C.P., M.D., Leicester General Hospital, Leicester; Nicholas Chalmers, F.R.C.R., Manchester Royal

Infirmary, Manchester; David Eadington, F.R.C.P., M.D., Hull Royal Infirmary, Hull; George Hamilton, F.R.C.S.,

M.D., Royal Free Hospital, London; Graham Lipkin, F.R.C.P., M.D., Queen Elizabeth Hospital, Birmingham;

Anthony Nicholson, F.R.C.R., Leeds General Infirmary, Leeds; and John Scoble, F.R.C.P., M.D., Guy's Hospital,

London — all in the United Kingdom)

Volume 361:1953-1962 November 12, 2009 Number 20

ASTRAL trial

• Randomized trial

• 806 patients

• 2 arms:

• revascularization in addition to

receiving medical therapy

• medical therapy alone.

ASTRAL trial

• Primary outcome was renal function

• Secondary outcomes were:

• blood pressure

• time to renal and major

cardiovascular events

• mortality

• median follow-up: 34 months

ASTRAL trial




• decrease in diastolic blood pressure was

smaller in the revascularization group

than in the medical-therapy group

ASTRAL trial

• Similar rates of

Renal events

• Major cardiovascular events

and death

Out of 403 patients

• Serious complications associated with

revascularization occurred in 23

patients, including 2 deaths and 3

amputations of toes or limbs




ASTRAL Conclusions

Renal stenting

Medical therapy




(p = ns) (p = ns)

7.4 8.2

CV mortality

Renal artery revascularization is not

superior to medical therapy alone

12 14

Hospitalization for fluid overload

heart failure


• “We found substantial risks but no

evidence of a worthwhile clinical

benefit from revascularization i in

patients with atherosclerotic

renovascular disease”

Presented by Dr. Philip Kalra at 2008 Society for Cardiovascular Angiography and

Interventions (SCAI) in partnership with the American College of Cardiology

(ACC). Chicago

• Prediction of renal functional outcome

following revascularization is a challenge

• Focus shifting from the degree of stenosis

to intrinsic parenchymal damage caused

by the hypertension

• Atheromatous embolism

• Down stream cytokine and/or

cholesterol crystal release

• Indicators of tissue viability

A renal resistance-index value of >80 reliably

identifies patients with renal-artery stenosis

in whom angioplasty or surgery will not

improve renal function, blood pressure, or

kidney survival.

Use of Doppler Ultrasonography to Predict the Outcome of Therapy for Renal-Artery Stenosis

Jorg Radermacher, M.D., et al, Volume 344: Number 6, 410-417 February 8, 2001 Hannover, Germany

• Etiology of microvascular renal disease

poorly understood.

• Probably microvascular stenosis

secondary to nephrosclerosis.

• Intimal thickening and fibrinoid necrosis

of the small arteries and arterioles.

• RI is the best parameter.

Renal Doppler Signals

Abuelo JG. Diagnosing vascular causes of renal failure. Ann Intern Med 1995;123:601-614.

Normal Cortical Flow

Abnormal Cortical Flow



• Many patients with RAS can achieve

stable blood pressure for many years

with medical management only.

• High mortality is from other

cardiovascular issues in these patients

with wide spread atherosclerotic


Chabova, V. et al. Outcomes of Atherosclerotic renal artery stenosis managed

without revascularization. Mayo Clinic Proceedings 2000, 75 pg 437.

Risks of treatment

Renal-artery angioplasty

• major complications in 10 to 15%

• death rate of 1 to 5%

Renal-artery surgery

• complication rate of 8 to 11%

• death rate of 2 to 8%.

Look beyond “lumenology”

Thank you

Understanding of parenchymal physiology

provides insight into predictors of outcome.


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