Renovascular

Disease:

Core
Curriculum

08-1
Renal Artery Stenosis

Etiology + Pathophysiology
Incidence
Diagnosis
Indications for
Revascularization
Treatment Options
- Medical Therapy
- PTA
- Surgical
Technical Considerations
Complications
Prognosis

08-2
 Causes of Ischemic Renal Disease
Atherosclerotic Renal Artery Stenosis
Fibromuscular dysplasia
Nephroangiosclerosis (HTN injury)
Diabetic nephropathy (small vessels)
Renal thromboembolic disease
Atheroembolic renal disease
#1 Renal Artery Stenosis
Aortorenal dissection
Post renal transplant RAS
Renal artery vasculitis
Trauma
Neurofibromatosis
Thromboangiitis obliterans
Scleroderma
#2 Fibromuscular Dysplasia

08-3
 Atherosclerotic Renal Artery Stenosis
Atherosclerosis accounts for approximately 90% of the
cases of RAS and is the predominant lesion detected in
patients >50 years of age
The presence and number of diseased coronary arteries
predicts the likelihood of ARAS
RAS resulting from atherosclerotic disease is common in
(18% to 20%) individuals undergoing coronary angiography
1

RAS resulting from atherosclerotic disease is even more

common (35% to 50%) in individuals undergoing peripheral
vascular angiography for occlusive disease of the aorta and
legs 2

1. Rihal et al Mayo Clin Proc 2002; 77: 309316

2. Olin et al J Vasc Surg 2002; 36: 443451 08-4
 Fibromuscular Dysplasia (FMD)

Unknown etiology
Second most common cause of RAS
Affects middle-aged women
More common in first-degree relatives and in the
presence of the ACE-I allele.
Renal artery involvement is seen in 60% of cases -
frequently bilateral compromise.
Progressive renal stenosis is seen in 37% of cases
and loss of renal mass in 63%

Grossmans Catheterization 7th Ed. pg. 562-603. 08-5

A. Classic string of beads appearance of fibromuscular dysplasia.
B. Intravascular ultrasound (IVUS) with a 40-MHz catheter demonstrating
multiple fine fibrous bands and foci of interband aneurysmal dilatation.
C. Translesional gradient measured between a 6Fr guide catheter placed
in the aorta and a 4F glide catheter placed in the distal renal artery. A
60-mm Hg resting gradient is demonstrated.

Grossmans Catheterization 7th Ed. pg. 562-603. 08-6

 Fibromuscular Dysplasia (FMD)
Treatment

Balloon angioplasty alone: FMD localized

within the main renal artery or its primary
branches
Stenting: Reserved for failure or complications
of balloon angioplasty
Surgery: FMD that involves multiple branch
vessels or is associated with aneurysmal
disease

Grossmans Catheterization 7th Ed. pg. 562-603. 08-7

D. Post-balloon angioplasty with a 4.5mm diameter balloon
demonstrating improvement in the angiographic appearance.
E. Intravascular ultrasound (IVUS) confirms the postangioplasty
improvement
F. Postprocedure IVUS demonstrates fracture of the fibrous bands,
resulting in resolution of the gradient seen before the procedure.

Grossmans Catheterization 7th Ed. pg. 562-603. 08-8

Schematic of Pressor Mechanisms Identified
in Renovascular Hypertension

Garovic VD, Textor SC. Circulation 2005;112:1362-1374 08-9

Goldblatt Model FMD Model: Atherosclerotic
(1934) Model (1970s):

No comorbidity Young patients Older patients

Hypertension out (female) Associated
of context Limited comorbidity comorbidity
Sole mechanism of Hypertension out off Hypertension in
hypertension context (detection) context
Sole mechanism of
Hypertension

08-10
Renal Artery Stenosis

Etiology + Pathophysiology
Incidence
Diagnosis
Indications for
Revascularization
Treatment Options
- Medical Therapy
- PTA
- Surgical
Technical Considerations
Complications
Prognosis

08-11
Prevalence of Renal Artery Stenosis
Most Common Cause of 2o HTN

70
50-59%
60

50

40
30%
30
15% 20%
20
5-10%
10

0
All HTN >50 yrs Pts with Acc Aortography
Pts With CAD HTN For PAD
ESRD

Rihal et al Mayo Clin Proc 2002; 77: 309316

Olin et al J Vasc Surg 2002; 36: 443451 08-12
 Prevalence of Renal Artery Stenosis
834 patients undergoing ultrasound screening

Mean age of 77 years

Significant (>60%) RAS in 6.8% of the study cohort
2 x as many men (9.1%) as women (5.5%, P=0.053)
RAS showed no association with ethnicity, even distribution among white
(6.9%) and black (6.7%) participants
RAS was significantly and independently associated with increasing age,
low high-density lipoprotein cholesterol levels, and increasing systolic
blood pressure.

Hansen et al J Vasc Surg 2002;36:443-51 08-13

 Severe Renal Artery Stenosis
Multivariate Associations
837 patients undergoing screening angiography

Buller CE et al JACC 2004: 43:1606 08-14

 Incidence of Renal Artery Stenosis at
Cardiac Catheterization
RAS
Study Authors Patients,n Any RAS,% >50%,% Bilateral, %
Aqel et al 90 NR 28 10
Weber-Mzell et al 177 25 11 8
Rihal et al 297 34 19 4
Vetrovec et al 116 29 23 29
Harding et al 1302 30 15 36
Jean et al 196 33 18 NR
MeanSD 2178 30.23.6 196 17.414.2
RAS indicates renal artery stenosis; NR, not reported.

White, C. J. Circulation. 2006;113:1464-1473 08-15

Approximately 50% of
renal artery stenoses
progress over time

08-16
 Progression Of RAS
Disease progression is associated with a decline in renal function

141 114 mol/L

97 44 mol/L
97 44 mol/L

Patients with normal renal arteries at baseline

Crowley JJ et al Am Heart Journal 1998;136:913 08-17

Progression of Renovascular Disease
Results in Renal Atrophy
204 kidneys in 122 patients with RAS
6 monthly serial duplex scanning
Defined as > 1cm reduction in length
2 year incidence of renal atrophy:

Normal RA 5.5%
< 60 % stenosis 11.7%
> 60 % stenosis 20.8%

Risk of atrophy increased by systolic hypertension

(> 180mm Hg) and a high peak systolic velocity

Caps et al, Kidney International, 1998

08-18
 4 Year Mortality
1235 cath lab patients screened for RAS > 50%

Multivariable P
Predictors OR Value

Age 1.72 0.004

Gender 1.91 0.029
GFR (per 5 ml/min) 0.86 0.004
SBP (per 5 mmHg) 1.08 0.005
Abdominal or 2.06 0.037
LE Disease
Carotid Disease 3.13 0.0007

Conlon PJ et al, J Am Soc Nephrol 9:252;1998 08-19

Renal Artery Stenosis

Etiology + Pathophysiology
Incidence
Diagnosis
Indications for
Revascularization
Treatment Options
- Medical Therapy
- PTA
- Surgical
Technical Considerations
Complications
Prognosis

08-20
Garovic VD, Textor SC Circulation. 2005;112:1362-1374 08-21
Renal Artery Obstruction
The Dilemma of Diagnosis

Atherosclerosis, hypertension and renal

insufficiency exist and co-exist commonly.
When there is renal artery stenosis:

Is it the cause of hypertension?

Is it the cause of renal insufficiency?
Will treatment improve either?
Will treatment prevent deterioration?

08-22
www.Cardiosource .com. ACC/AHA Guidelines 08-23
www.Cardiosource .com. ACC/AHA Guidelines 08-24
Noninvasive diagnostic modalities
Renal Artery Ultrasound

Body habitus dependent

Operator dependent
May miss accessory arteries
No additional anatomical information
Physiological information
Allows post intervention surveillance

08-25
74 y/o man with difficult to
control HTN

08-26
 Duplex Assessment of RAS
Duplex Criteria Stenosis

RAR<3.5 and 0-59%

PSV<200 cm/sec
RAR >3.5 and 60-99%
PSV>200 cm/sec
RAR>3.5 and 80-99%
EDV > 150 cm/sec
Absence of flow and low Occluded
amplitude parenchymal
signal

08-27
 Power Doppler image of a stenosis of right RA. The
arrows indicate the stenosis.

Manganaro et al. Cardiovascular Ultrasound 2004 2:1 08-28

Noninvasive diagnostic modalities
Digital Subtraction Angiography

40 y/o woman with

well controlled HTN

08-29
 Noninvasive diagnosis: MRA

Identifies accessory renal

arteries
Provides additional
anatomical information
No radiation
No nephrotoxic contrast
Allows 3-D reconstruction
May overcall lesions
Looses accuracy in distal
segments (FMD) Mild (30%) left RAS and severe
(90%) right RAS in 70-year-old
man

Fenchel, M. et al. Radiology 2006;238:1013-1021 08-30

 Normal renal arteries in a 61 y/o man

Severe stenosis of left renal artery in a 72 y/o man

Herborn, C. U. et al. Radiology 2006;239:263-268 08-31

40 y/o woman with well controlled HTN

08-32
74 y/o man with difficult to control HTN

Motion artifact

08-33
Renal Artery Stenosis

Etiology + Pathophysiology
Incidence
Diagnosis
Indications for
Revascularization
Treatment Options
- Medical Therapy
- PTA
- Surgical
Technical Considerations
Complications
Prognosis

08-34
 Reasons to Revascularize
Atherosclerotic Renovascular Disease
Treat Symptoms
Prevent Future Illness
Lower BP
Preserve Renal Function
Bystander Effects
- Prevent Death
- Prevent MI
- Prevent CHF
- Prevent CVA

08-35
Indications for Revascularization of RAS
1. Resistant hypertension
- Failure of medical therapy despite full doses of 3 drugs, including
diuretic
- Compelling need for ACE inhibition/angiotensin blockade with
angiotensin-dependent GFR
2. Progressive renal insufficiency with salvagable kidneys
- Recent rise in serum creatinine
- Loss of GFR during antihypertensive therapy (e.g., ACEI)
- Evidence of preserved diastolic blood flow (low resistive index)
3. Circulatory congestion, recurrent flash pulmonary
edema
4. Refractory congestive heart failure with bilateral renal
artery stenosis

Circulation 2005;112:1362-1374. 08-36

 Who Will Benefit:
Renal Resistive Index
Reflection of intrarenal vascular surface area
and resistance
Calculated using Doppler U/S
Resistive Index
[1-(EDV/PSV)]x100
4950 patients underwent U/S calculation of
renal resistive index
138 RAS patients treated
Followed for improvement in BP and Cr

Radermacher et al NEJM. 2001;344:2244-49

08-37
 Outcomes Predicted By RRI

Radermacher et al NEJM. 2001;344:2244-49

08-38
 Renal Revascularization
Useful when:
Renal artery stenosis is SEVERE, and...
Renal function is salvageable
Preserved size
Preserved intrinsic vasculature (low RI)
Not useful when:
Renal artery stenosis is not severe
Renal function is unsalvageable
Unknown:
Prophylactic use
Value of screening
Role of atheroembolization / Protection

08-39
Renal Artery Stenosis

Etiology + Pathophysiology
Incidence
Diagnosis
Indications for
Revascularization
Treatment Options
- Medical Therapy
- PTA
- Surgical
Technical Considerations
Complications
Prognosis

08-40
Goals Of Renal Artery Revascularization

Improve control of hypertension

Preserve or restore renal function

Treat other potential adverse physiologic

effects of severe renal artery stenosis
(congestive heart failure, recurrent flash
pulmonary edema, and angina)

08-41
 Pharmacological Treatment of
Renal Artery Stenosis
ACE inhibitors are effective medications for
treatment of hypertension associated with RAS.
I IIa IIb III
Calcium-channel blockers are effective
medications for treatment of hypertension
associated with unilateral RAS.
Beta-blockers are effective medications for
treatment of hypertension associated with RAS.

I IIa IIb III Angiotensin receptor blockers are effective

medications for
treatment of hypertension
associated with unilateral RAS.

ACC/AHA Guidelines 08-42

Catheter- Based Interventions for RAS

Renal stent placement is indicated for

I IIa IIb III
ostial atheroesclerosic RAS lesions that
meet the clinical crietria for intervention.

Balloon angioplasty with bail-out stent

placement if necessary is recommended
for fibromuscular dysplasia lesions.

ACC/AHA Guidelines 08-43

 Renal Artery Stent Placement

Ostial
2 mm into atheroma
aorta

Stent with
protrusion into
aortic lumen

Zeller T. Journal of Interv Card 18 (6), 497-506. 08-44

 Renal Artery Stenting: Results
Published series before 1998

1188 patients, mean follow up 16 months

Hypertension cured 20%

69%
Hypertension improved 49%
Renal function improved 30%
78%
Renal function stabilized 38%

Leertouwer et al Radiology 2000, 216 78-85 08-45

 Renal Artery Stenting Studies
Meta-analysis of 349 pts in 8 clinical series
- Hypertension improved in 56%; cured in 10%
- Renal artery function improved in 27%;
stabilized in 38%
- Restenosis occurred in 16%
- Major complications in 4.9
Palmaz JC et al J Vasc Intervent Radiol 1998;9:539-43
DRASTIC Trial
- 106 patients treated with PTA or medical therapy
- Although no difference in outcomes, stenting reserved for bailout,
44% of medical therapy crossed over to PTA due to HTN, occlusion seen in
16% of medical treated patients
Van Jaarsveld BC et al. N Engl J Med 2000; 342: 1007-1014

08-46
Superiority of renal artery stent compared with balloon
angioplasty for procedure success and restenosis rates
Percent

Procedure Success Restenosis

White CJ Circulation 2006;113:1464-1473 08-47

Surgery for Renal Artery Stenosis

Endarterectomy

Aortorenal bypass

Extra-anatomic bypass using

hepatorenal, splenorenal, ileorenal, or
superior mesenteric artery renal
anastomosis.

08-48
 Surgery for Renal Artery Stenosis

Fibromuscular dysplastic RAS with clinical indications,

I IIa IIb III especially those exhibiting complex disease that
extends into the segmental arteries and those having
macroaneurysms.
Atheroeclerotic RAS and clinical indications for
intervention, especially those with multiple small renal
arteries or early primary branching of the main renal
artery.

I IIa IIb III Atherosclerotic RAS in combination with pararenal

aortic reconstructions (in treatment of aortic
aneurysms or severe aortoiliac occlusive diseease.

ACC/AHA Guidelines 08-49

Renal Artery Stenosis

Etiology + Pathophysiology
Incidence
Diagnosis
Indications for
Revascularization
Treatment Options
- Medical Therapy
- PTA
- Surgical
Technical Considerations
Complications
Prognosis

08-50
 Renal Arteriography
Abdominal Aortogram: identification of ostia of the renal
arteries and accessory renal arteries (25% of
population)
Arteriography should include both the arterial phase
and the nephrographic phase
Disease involving renal bifurcations require cranial or
caudal angulation to open out the lesion
Evidence of aortic atheroma: technique of no-touch
angiography is recommended
IVUS provides a further method of renal
artery evaluation for indeterminate lesions

08-51
 Brachial Approach

For renal arteries that are

oriented cephalad.
When the aorta is occluded
distally or the renal artery
takeoff is severely angulated
Proximal renal artery
segment initially courses
inferiorly and posteriorly
braquial approach allows
more coaxial alignment.
Greater incidence of
vascular site complications

Zeller T. Journal of Interventional Cardiology 18 (6), 497-506

08-52
 Femoral Approach
Renal artery angioplasty and stenting are usually
performed via retrograde femoral approach.
When the real artery origin is oriented horizontally
or caudally with respect to the aorta, femoral
approach is preferred.

08-53
Renal Artery Stenosis

Etiology + Pathophysiology
Incidence
Diagnosis
Indications for
Revascularization
Treatment Options
- Medical Therapy
- PTA
- Surgical
Technical Considerations
Complications
Prognosis

08-54
 Registry Stent Complications
Major
Renal Stents Number Death Dialysis Compls

Blum 74 0 0 0
Harjai 88 0 0 0
Tuttle 148 0 0 4.1
Rocha-Singh 180 0.6 0 2.6
Burket 171 0 0.7 0.7
White 133 0 0 0.75
Borros 163 0.6 0 1.80
Total 957 <1% <1% 1.4%

08-55
Complications Of Percutaneous Renal
Revacularization

Atheroembolism into the renal or peripheral

vascular bed cholesterol embolization
Dissection of renal artery or the wall of the
aorta
Acute or delayed thrombosis
Infection
Rupture of renal artery
Renal perforation

08-56
 Complication Rates for Renal Stent
Placement
Patients, Major
Study Authors n Death, % Dialysis, % complications, %
Rocha-Singh et al 180 0.6 0 2.6
Tuttle et al 148 0 0 4.1
White et al 133 0 0 0.75
Burket et al 171 0 0.7 0.7
Dorros et al 163 0.6 0 1.8
Total 795 <1% <1% 2.0%

Major complications include death, myocardial infarction, emergency surgery,

need for dialysis, or blood transfusion.

White et al, Circulation. 2006;113:1464-1473

08-57
Atheroembolization Protection

What is the cause of

deterioration in renal
function after
revascularization?
Iodinated contrast?
Atheroembolization?
Something else?

08-58
Filterwire Embolic Protection

08-59
 Renal Artery Embolization

A, Baseline selective renal angiogram showing tight ostial

stenosis with normal filling of the renal arteries to the cortex

B, Poststent angiogram with poor filling of the distal renal

arteries caused by embolization

White CJ Circulation 2006;113:1464-1473 08-60

Renal Artery Stenosis

Etiology + Pathophysiology
Incidence
Diagnosis
Indications for
Revascularization
Treatment Options
- Medical Therapy
- PTA
- Surgical
Technical Considerations
Complications
Prognosis

08-61
 Favorable Predictors
Successful Outcome For Control Of Hypertension

Rapid acceleration of hypertension over the

prior weeks or months
Presence of malignant hypertension
Hypertension in association with flash
pulmonary edema
Contemporaneous rise in serum creatinine
Development of azotemia in response to ACE
inhibitors administered for control of
hypertension.

08-62
 Favorable Predictors
Successful Salvage Or Preservation Of Renal Function

Recent rapid rise in creatinine, unexplained by

other factors
Azotemia resulting from ACE inhibitors
Absence of diabetes or other cause of intrinsic
kidney disease
Presence of global renal ischemia, wherein the
entire functioning renal mass is subtended by
bilateral critically narrowed renal arteries or a
vessel supplying a solitary kidney.

08-63
 Unfavorable Predictors

Renal atrophy demonstrated by kidney

length <7.5 cm on ultrasound
High renal resistance index detected by
duplex ultrasound
Proteinuria > 1gm/day
Hyperuricemia
Creatinine clearance <40 mL/minute

08-64
Outcomes Following Renal Stenting
Major Predictor was the RRI

Radermacher et al NEJM. 2001;344:2244-49

08-65
 Outcomes Following Renal Stenting
Major Predictor was the RRI at 32 months

RRI < 80 RRI > 80

N = 96 N = 35

MAP 10 mm Hg 94% 3%
Cr Cl 10% 3% 80%
Dialysis 3% 46%
Death 3% 29%
P < 0.001 for all outcomes

Radermacher et al NEJM. 2001;344:2244-49

08-66
 Stabilization of Renal Function

Harden et al. Lancet 1997;349:1133 08-67

Cardiovascular Outcomes in Renal
Atherosclerotic Lesions (CORAL)
Enrollment: April 2004 March 2010

1080 patients with

RAS >60% and hypertension (>155 mmHg on 2 meds)
1:1 Randomization to:

Optimal medical therapy alone vs

stenting with optimum medical therapy
Composite cardiovascular and renal endpoint:
Cardiovascular or renal death, MI, hospitalization for
CHF, stroke, doubling of serum creatinine level, need
for renal replacement therapy

08-68
Renal Artery Stenosis

Etiology + Pathophysiology
Incidence
Diagnosis
Indications for
Revascularization
Treatment Options
- Medical Therapy
- PTA
- Surgical
Technical Considerations
Complications
Prognosis

08-69