management of renal artery stenosis kent mackenzie, md division of vascular surgery mcgill...
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Management of Renal Artery Stenosis
Kent MacKenzie, MD
Division of Vascular SurgeryMcGill UniversityMontreal, Quebec
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Disclosures
None
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Atherosclerotic RAS• Often orificial/ostial• Associated aortic atherosclerosis• Associated atherosclerosis elsewhere
– Coronary– Carotid– Peripheral
• Fibrointimal Hyperplasia (FMD)
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Atherosclerotic RAS
• Clinical Consequences– Hypertension– Ischemic nephropathy – Chronic renal failure– Dialysis
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Hypertension
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Hypertension1.Picture Renin-AII-Ald
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Angiotensin II• Vasoconstriction
• Sodium Retention
• Aldosterone Release
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Sustained HTN• Adaptive changes PVR• Heart• Arteries
• Endothelial dysfunction• Nitrous oxide
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The presence of hypertension is considered a prerequisite for renal artery intervention.
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Diagnosis of RAS• Hemodynamically significant lesion in renal
artery in a patient with HPTN– Pressure gradient
• Diagnosis depends on identifying:– a pressure gradient
– surrogate of a pressure gradient• Functional surrogate
• Imaging surrogate
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Functional Studies
• Intravenous Pyelography• Differential Renal Function Studies• Plasma Renin Activity• Simulated Plasma Renin Activity• Renal Vein Renin• Catpopril Renal Scintography
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Functional Studies
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Functional Studies - Screening
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Imaging Diagnosis• Imaging surrogates for hemodynamic
RAS– Duplex ultrasound – CT– MRA– Angiography
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•CT Angio– Minimally invasive– Calcification artifact
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•MRA–NSF–?overestimates–experience
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•Duplex Ultrasound–PSV criteria–PSV RA/Aorta ratios
Picture
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•Angiography– ? Smaller contrast load– Allows intervention
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Imaging Diagnosis of RAS
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In Practice• High likelihood of RAS• Good clinical indications for
intervention– Duplex ultrasound– Ad-hoc Diagnostic +/- Therapeutic renal
arteriography
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Indications for Revascularization
The presence of hypertension is considered a prerequisite for renal artery intervention.
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Revascularization• Potential Indications for renal revascularization
– Incidental , asymptomatic RAS with need for aortic reconstruction
– RAS with renal dysfunction alone
– RAS with hypertension– RAS with hyperpertension and renal dysfunction
– RAS with angina– RAS with recurrent flash pulmonary edema
Chronic HPTN issues
Acute HPTN issues
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Revascularization with aortic surgery (prophylactic)
• 69 y.o. patient requires:–Open AAA repair–Endo AAA repair–Aortofemoral bypass for occlusive dx.
• Incidental imaging finding of severe RAS• No severe HPTN at diagnosis
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Revascularization with aortic surgery (prophylactic)
• 100 hypothetical patients with unsuspected RAS who will undergo aortic surgery– 44% (44 patients) lesion progression and RVH
• 36% (16 patients) may develop preventable reduction in renal function
• 66% (11 patients) will demonstrate restored function with delayed renal treatment
Hansen KJ et al
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Revascularization with aortic surgery (prophylactic)
• Therefore only 5 patients (5%) will gain a unique benefit from prophylactic renal artery repair
• Risk of adverse event with combined aortic/renal revasc.– 5-6% mortality in the best hands– 3-4% late failure of operative repair
• Therefore, prophylactic renal revasc. will potentially result in benefit in 5% of patients yet an adverse outcome in 10%
Hansen KJ et al
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Revascularization with aortic surgery (prophylactic)
• Prophylactic renal revascularization alone or in conjunction with aortic reconstruction is therefore not indicated– Surgical reconstruction
– Catheter-based reconstruction
Hansen KJ et al
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Renal Insufficiency and RAS
• The absence of hypertension in a patient with
RAS and excretory dysfunction suggests the
presence of severe parenchymal disease
• Without HPTN, response to revascularization is
poor
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RAS and Hypertension alone
• Treatment is empiric• Expectation of clinical improvement is less• Unilateral vs. Bilateral RAS• Hypertension response is poorly predictable
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• Accumulated experience has resulted in a paradigm shift in approach to selecting patients for intervention
• Surgical literature PTA
• RAS and severe HPTN as a pre-intervention predictor of response
• Changes in renal function post-intervention being the short-term outcome
• Improvements in all-cause cardiovascular outcomes being the outcome of interest in trials evaluating RA intervention
Hypertension with Renal Insufficiency
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Hypertension with Renal Insufficiency
All patients
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Hypertension with Renal Insufficiency
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Hypertension with Renal Insufficiency
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• Treatment of hemodynamically significant RAS in a patient with:– Hypertension (severe)– Rapidly progressive decline in renal function– Salvageable renal mass
• Surgical literature suggests expectation of improved BP control and reduction in rate of functional loss
Hypertension with Renal Insufficiency
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RAS with angina or pulm edema
• Acute myocardial strain• Acute episodes of severe hypertension• Multiple case-series suggesting significant
stabilzation of cardiac status after renal revascularization
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• Surgical Revascularization– Renal/aortic endarterectomy– Renal artery bypass
• Direct– Aortorenal bypass, iliorenal bypass– Renal artery reimplantation
• Indirect– Hepatorenal bypass– Splenorenal bypass– Mesorenal bypass
Options for Intervention
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• Surgical Revascularization– Ex-vivo reconstruction
• To be considered in:
–Solitary kidney
–Complex renal artery branch reconstructions
Options for Intervention
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• Percutaneous Treatment– Renal artery angioplasty
– Renal artery angioplasty with provisional/selective
stenting
– Renal artery stenting
Options for Intervention
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• No controlled studies comparing angioplasty vs. stenting
• Limited data comparing angioplasty/stenting to surgical revascularization
• No strong evidence demonstrating superiority of surgical revascularization over medical therapy
• No strong evidence demonstrating superiority of renal angioplasty/stenting over medical therapy
• Uncontrolled, non-randomized data supports the use of renal revascularization in high-risk groups
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• Side-by-side comparison of large surgical series and renal angioplasty series suggests better durability and improvements in renal insufficiency in surgical patients
• Comes at the cost of higher peri-procedural morbidity and mortality
• So percutaneous treatments selected in most patients other than those with need for aortic reconstruction or with contraindications for PTA
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Randomized Trials
Percutaneous Renal Artery Intervention
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• EMMA Trial, 1998• Unilateral atherosclerotic RAS• Normal renal function• 59 patients randomized• Primary outcomes
– Ambulatory blood pressure (ABP)• Secondary outcomes
– Treatment score– Complications
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• No difference in ABP• But lower Treatment Score (fewer meds) in
angioplasty group• Higher procedural complication in angioplasty group
(26% vs. 8%)• Criticisms:
– 1/3 eligible screened patients not enrolled because of patient or physician preference for angioplasty
– Protocol called for antihypertensives in angioplasty group if BP control ‘not optimal’• Study design biased to not demonstrate
primary outcome
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• Scottish/Newcastle study, 1998• Atherosclerotic uni- or bilat- RAS• 135 patients eligible
– Only 54 randomized– Non-randomized patients included for analysis
• Primary endpoints– Mean BP and serum creatinine
• 4 weeks and 6 months
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• Mean BP improved in medical and intervention arms during study period
• Mean BP after angioplasty improved only in the bilateral, randomized group
• Reduced hypertensive medication usage from 2.8 to 2.3 drugs in angioplasty groups
• No differences in renal function between groups
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• DUTCH renal angioplasty trial, 2000• 106 patients with atherosclerotic RAS
randomized• Inclusion:
– RAS >50%• Diast. BP >95 mm Hg• Worsening Creat on ACE inhibitor
• Primary Endpoints– Systolic and diastolic BP at 3 and 12 months
• Secondary Endpoints– Number of antihypertensive medications
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• RESULTS• Blood pressure no different between groups• Number of drugs in angioplasty group
diminished (1.9 vs. 2.5)• Criticisms:
– Study design aimed for diastolic BP 95 mmHg• Keeping drug numbers same might have led to
improved BP in angioplasty group– 50% of patients in medical arm crossed over to
angioplasty within 3 months of randomization
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The Big Hurt
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• Patients where role of angioplasty was unclear
• BP was not severe (2 meds, mean 149/76)
• 40% patients had stenosis <70%
• Primary end-point decline in renal function
• 25% had normal renal function
• Only 12% had recent rapid decline in fcn.
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• Patients excluded were those most likely to gain benefit– Patients with:
• High-grade stenosis
• Poorly controlled hypertension
• Rapidly declining renal function
• Likely significant selection bias based on lack of equipoise to randomize patients
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• Also identified:– 27% of patient in the medical arm had an
improvement of more than 10 mol/L during the period of study
– This finding helps explain in part, the results of revascularization in uncontrolled, non-randomized cohort studies of renal angioplasty and surgical revascularization
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The Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) Study: Rationale and MethodsTimothy P. Murphy, MD, Christopher J. Cooper, MD, Lance D. Dworkin, MD, William L. Henrich, MD, John H. Rundback, MD, Alan H. Matsumoto, MD, Kenneth A. Jamerson, MD, Ralph B. D'Agostino, PhD
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Still not in publication
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Treatment Recommendations• Medical Therapy
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Treatment Recommendations• Interventional Therapy
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Treatment Recommendations• Interventional Therapy
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Treatment Recommendations• Interventional Therapy
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Treatment Recommendations• Interventional Therapy
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Treatment Recommendations• Interventional Therapy
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Treatment Recommendations• Surgical Therapy
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Treatment Recommendations• Surgical Therapy
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Summary
Renal Revascularization
• Sound concept to treat a serious problem
• Basic science observations and observational
studies support its role in treating RAS
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Intervention– Severe bilateral RAS with severe hypertension
– Selected unilateral severe RAS with severe hypertension
– Severe RAS with renal dysfunction and HPTN• If rapid progressive over short period
– RAS with angina• Associated with severe hypertension
– RAS with CHF• Coexistent hypertension, flash pulmonary edema
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Angioplasty/Stent
– First-line of intervention in the majority of cases
• Reduced procedural morbidity and mortality
– Magnitude of benefit and durability
– More evidence is required
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Surgical Reconstruction• Indication for renal revascularization and concomitant
indication for aortic reconstruction– Aneurysm
– Occlusive disease
• Renal occlusive disease involving aorta or renal artery
bifurcation/branches
• Concomitant renal artery/branch aneurysm
• Young patient with good operative risk
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Thank You