Renovascular Disease: Core Curriculum

08-1

Renovascular Disease:

Core Curriculum

08-2

Renal Artery StenosisRenal Artery Stenosis

Etiology + PathophysiologyIncidence DiagnosisIndications for RevascularizationTreatment Options

- Medical Therapy- PTA- Surgical

Technical ConsiderationsComplicationsPrognosis

08-3

Causes of Ischemic Renal DiseaseCauses of Ischemic Renal Disease

• Atherosclerotic Renal Artery Stenosis• Fibromuscular dysplasia • Nephroangiosclerosis (HTN injury)• Diabetic nephropathy (small vessels)• Renal thromboembolic disease• Atheroembolic renal disease• Aortorenal dissection• Post renal transplant RAS • Renal artery vasculitis• Trauma• Neurofibromatosis• Thromboangiitis obliterans• Scleroderma

#1 Renal Artery Stenosis

#2 Fibromuscular Dysplasia

08-4

Atherosclerotic Renal Artery StenosisAtherosclerotic 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: 309–316

2. Olin et al J Vasc Surg 2002; 36: 443–451

08-5

Fibromuscular Dysplasia (FMD)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.

08-6

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.


08-7

Fibromuscular Dysplasia (FMD)Fibromuscular Dysplasia (FMD)TreatmentTreatment

• 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


08-8

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.


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

Schematic of Pressor Mechanisms Identified Schematic of Pressor Mechanisms Identified in Renovascular Hypertensionin Renovascular Hypertension

08-10

““Goldblatt” Model Goldblatt” Model (1934)(1934)

FMD Model: “Atherosclerotic” Model (1970’s):

•No comorbidityNo comorbidity

•Hypertension outHypertension out

of contextof context

•Sole mechanism of Sole mechanism of

hypertension

•Young patients

(female)

•Limited comorbidity

•Hypertension out off

context (detection)

•Sole mechanism of

Hypertension

•Older patients

•Associated

comorbidity

•Hypertension in

context

08-11

Renal Artery Stenosis

Etiology + Pathophysiology Incidence

DiagnosisIndications for RevascularizationTreatment Options



08-12

Prevalence of Renal Artery StenosisPrevalence of Renal Artery StenosisMost Common Cause of 2Most Common Cause of 2oo HTN HTN

0

10

20

30

40

50

60

70

All HTNPts

>50 yrsWith

ESRD

Pts withCAD

AccHTN

AortographyFor PAD

5-10%

15% 20%

30%

50-59%

Rihal et al Mayo Clin Proc 2002; 77: 309–316

Olin et al J Vasc Surg 2002; 36: 443–451

08-13

Prevalence of Renal Artery StenosisPrevalence of Renal Artery Stenosis 834 patients undergoing ultrasound screening 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

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

Severe Renal Artery Stenosis Severe Renal Artery Stenosis Multivariate AssociationsMultivariate Associations

837 patients undergoing screening angiography837 patients undergoing screening angiography

08-15

Incidence of Renal Artery Stenosis at Incidence of Renal Artery Stenosis at Cardiac Catheterization Cardiac Catheterization

Study Authors Patients,n Any RAS,%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

Mean±SD 2178 30.2±3.6 19±6 17.4±14.2

RAS indicates renal artery stenosis; NR, not reported.

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

08-16

Approximately 50% of renal artery stenoses progress over time

08-17

Progression Of RASProgression Of RASDisease progression is associated with a decline in renal functionDisease progression is associated with a decline in renal function

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

97 ± 44 μmol/L97 ± 44 μmol/L

141 ± 114 μmol/L

Patients with normal renal arteries at baseline

08-18

Progression of Renovascular Disease Progression of Renovascular Disease Results in Renal AtrophyResults 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:2 year incidence of renal atrophy:

Normal RANormal RA 5.5%5.5%

< 60 % stenosis< 60 % stenosis 11.7%11.7%

> 60 % stenosis> 60 % stenosis 20.8%20.8%

Risk of atrophy increased by systolic hypertension Risk of atrophy increased by systolic hypertension

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

Caps et al, Kidney International, 1998

08-19

4 Year Mortality4 Year Mortality1235 cath lab patients screened for RAS > 50%1235 cath lab patients screened for RAS > 50%

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

MultivariablePredictors

AgeGenderGFR (per 5 ml/min)SBP (per 5 mmHg)Abdominal or LE DiseaseCarotid Disease

OR

1.721.910.861.082.06

3.13

PValue

0.0040.0290.0040.0050.037

0.0007

08-20

Renal Artery Stenosis

Etiology + PathophysiologyIncidence

DiagnosisIndications for RevascularizationTreatment Options



08-21Garovic VD, Textor SC Circulation. 2005;112:1362-1374

08-22

Renal Artery ObstructionRenal Artery ObstructionThe Dilemma of DiagnosisThe Dilemma of Diagnosis

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

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

08-23www.Cardiosource .com. ACC/AHA Guidelines

08-24www.Cardiosource .com. ACC/AHA Guidelines

08-25

Noninvasive diagnostic modalitiesNoninvasive diagnostic modalities Renal Artery Ultrasound Renal Artery Ultrasound

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

08-26

74 y/o man with difficult to control HTN

08-27

Duplex Assessment of RASDuplex Assessment of RAS

Duplex Criteria Stenosis

RAR<3.5 and

PSV<200 cm/sec

0-59%

RAR >3.5 and

PSV>200 cm/sec

60-99%

RAR>3.5 and

EDV > 150 cm/sec

80-99%

Absence of flow and low amplitude parenchymal signal

Occluded

08-28

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

Manganaro et al. Cardiovascular Ultrasound 2004 2:1

08-29

40 y/o woman with well controlled HTN

Noninvasive diagnostic modalitiesNoninvasive diagnostic modalitiesDigital Subtraction AngiographyDigital Subtraction Angiography

08-30

Noninvasive diagnosis: MRANoninvasive 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

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

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

Normal renal arteries in a 61 y/o man

08-32

40 y/o woman with well controlled HTN40 y/o woman with well controlled HTN

08-33

74 y/o man with difficult to control HTN74 y/o man with difficult to control HTN

Motion artifact

08-34


Etiology + PathophysiologyIncidence DiagnosisIndications forRevascularizationTreatment Options

- Medical Therapy

- PTA- Surgical


08-35

Reasons to Revascularize Reasons to Revascularize

Atherosclerotic Renovascular DiseaseAtherosclerotic Renovascular Disease

Treat SymptomsTreat Symptoms

Prevent Future IllnessPrevent Future Illness• Lower BPLower BP• Preserve Renal FunctionPreserve Renal Function• “ “Bystander” EffectsBystander” Effects

- - Prevent DeathPrevent Death

-- Prevent MI Prevent MI

- Prevent CHF - Prevent CHF

- Prevent CVA- Prevent CVA

08-36

Indications for Revascularization of RASIndications for Revascularization of RAS

Circulation 2005;112:1362-1374.

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

08-37

Who Will Benefit: Who Will Benefit: Renal Resistive IndexRenal 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

08-38

Outcomes Predicted By RRIOutcomes Predicted By RRI


08-39

Renal RevascularizationRenal 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

08-40





08-41

Goals Of Renal Artery RevascularizationGoals 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)

08-42

• •

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

• ACE inhibitors are effective medications for treatment of hypertension associated with RAS.

• 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.

Pharmacological Treatment of Pharmacological Treatment of Renal Artery StenosisRenal Artery Stenosis

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII • Angiotensin receptor blockers are effective medications for treatment of hypertension associated with unilateral RAS.

ACC/AHA Guidelines

08-43

Catheter- Based Interventions for RASCatheter- Based Interventions for RAS

• Renal stent placement is indicated for 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

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

Renal Artery Stent PlacementRenal Artery Stent Placement

Ostial atheroma

Stent with protrusion into aortic lumen

2 mm into aorta

08-45

Renal Artery Stenting: ResultsRenal Artery Stenting: ResultsPublished series before 1998Published series before 1998

Leertouwer et al Radiology 2000, 216 78-85

1188 patients, mean follow up 16 months

Hypertension cured 20%Hypertension improved 49%Renal function improved 30%Renal function stabilized 38%

69%

78%

08-46

Renal Artery Stenting StudiesRenal 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

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

Superiority of renal artery stent compared with balloon Superiority of renal artery stent compared with balloon angioplasty for procedure success and restenosis ratesangioplasty for procedure success and restenosis rates

Restenosis

Per

cen

t

Procedure Success

08-48

Surgery for Renal Artery StenosisSurgery for Renal Artery Stenosis

• Endarterectomy

• Aortorenal bypass

• Extra-anatomic bypass using hepatorenal, splenorenal, ileorenal, or superior mesenteric artery – renal anastomosis.

08-49

Surgery for Renal Artery StenosisSurgery for Renal Artery Stenosis

• Atherosclerotic RAS in combination with pararenal aortic reconstructions (in treatment of aortic aneurysms or severe aortoiliac occlusive diseease.

• Fibromuscular dysplastic RAS with clinical indications, 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.



ACC/AHA Guidelines

08-50





08-51

Renal ArteriographyRenal 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

08-52

Brachial ApproachBrachial 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

08-53

Femoral ApproachFemoral 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.

08-54



- Medical Therapy

- PTA- Surgical


08-55

Registry Stent Complications Registry Stent Complications

Renal Stents

Blum

Harjai

Tuttle

Rocha-Singh

Burket

White

Borros

Total

Number

74

88

148

180

171

133

163

957

Death

0

0

0

0.6

0

0

0.6

<1%

Dialysis

0

0

0

0

0.7

0

0

<1%

Major

Compls

0

0

4.1

2.6

0.7

0.75

1.80

1.4%

08-56

Complications Of Percutaneous Renal Complications Of Percutaneous Renal RevacularizationRevacularization

• 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

08-57

Complication Rates for Renal Stent Complication Rates for Renal Stent Placement Placement

Study AuthorsPatients,

n Death, % Dialysis, %Major

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

08-58

Atheroembolization ProtectionAtheroembolization Protection

What is the cause of What is the cause of deterioration in renal deterioration in renal function after function after revascularization?revascularization?

•Iodinated contrast?Iodinated contrast?

•Atheroembolization?Atheroembolization?

•Something else?Something else?

What is the cause of What is the cause of deterioration in renal deterioration in renal function after function after revascularization?revascularization?

•Iodinated contrast?Iodinated contrast?

•Atheroembolization?Atheroembolization?

•Something else?Something else?

08-59

Filterwire Embolic ProtectionFilterwire Embolic Protection

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

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

Renal Artery EmbolizationRenal Artery Embolization

08-61





08-62

Favorable PredictorsFavorable PredictorsSuccessful Outcome For Control Of HypertensionSuccessful 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.

08-63

Favorable PredictorsFavorable PredictorsSuccessful Salvage Or Preservation Of Renal FunctionSuccessful 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.

08-64

Unfavorable PredictorsUnfavorable 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

08-65

Outcomes Following Renal StentingOutcomes Following Renal StentingMajor Predictor was the RRIMajor Predictor was the RRI


08-66

Outcomes Following Renal StentingOutcomes Following Renal StentingMajor Predictor was the RRI at 32 monthsMajor Predictor was the RRI at 32 months


↓ MAP ≥ 10 mm Hg

↓ Cr Cl ≥ 10%

Dialysis

Death

RRI < 80N = 96

94%

3%

3%

3%

RRI > 80N = 35

3%

80%

46%

29%

P < 0.001 for all outcomes

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

Stabilization of Renal FunctionStabilization of Renal Function

08-68

Cardiovascular Outcomes in Renal Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL)Atherosclerotic Lesions (CORAL)

Enrollment: April 2004 – March 2010

1080 patients withRAS >60% and hypertension (>155 mmHg on ≥ 2 meds)

Composite cardiovascular and renal endpoint: Cardiovascular or renal death, MI, hospitalization for CHF, stroke, doubling of serum creatinine level, need

for renal replacement therapy

Optimal medical therapy alone vs stenting with optimum medical therapy

1:1 Randomization to:

08-69





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Renovascular Disease: Core Curriculum