renal function

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Management of Renal Artery
Stenosis
Kent MacKenzie, MD
Division of Vascular Surgery
McGill University
Montreal, Quebec
Disclosures
None
Atherosclerotic RAS
• Often orificial/ostial
• Associated aortic atherosclerosis
• Associated atherosclerosis elsewhere
– Coronary
– Carotid
– Peripheral
• Fibrointimal Hyperplasia (FMD)
Atherosclerotic RAS
• Clinical Consequences
– Hypertension
– Ischemic nephropathy
– Chronic renal failure
– Dialysis
Hypertension
Hypertension
1.Picture Renin-AII-Ald
Angiotensin II
• Vasoconstriction
• Sodium Retention
• Aldosterone Release
Sustained HTN
• Adaptive changes  PVR
• Heart
• Arteries
• Endothelial dysfunction
•  Nitrous oxide
The presence of hypertension is considered a
prerequisite for renal artery intervention.
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
Functional Studies
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•
•
•
•
•
Intravenous Pyelography
Differential Renal Function Studies
Plasma Renin Activity
Simulated Plasma Renin Activity
Renal Vein Renin
Catpopril Renal Scintography
Functional Studies
Functional Studies - Screening
Imaging Diagnosis
• Imaging surrogates for hemodynamic
RAS
– Duplex ultrasound
– CT
– MRA
– Angiography
•CT Angio
– Minimally invasive
– Calcification artifact
•MRA
–NSF
–?overestimates
–experience
•Duplex Ultrasound
–PSV criteria
–PSV RA/Aorta ratios
Picture
•Angiography
– ? Smaller contrast load
– Allows intervention
Imaging Diagnosis of RAS
In Practice
• High likelihood of RAS
• Good clinical indications for
intervention
– Duplex ultrasound
– Ad-hoc Diagnostic +/- Therapeutic renal
arteriography
Indications for Revascularization
The presence of hypertension is considered a
prerequisite for renal artery intervention.
Revascularization
• Potential Indications for renal revascularization
– Incidental , asymptomatic RAS with need for aortic
reconstruction
– RAS with renal dysfunction alone
– RAS with hypertension
Chronic HPTN issues
– RAS with hyperpertension and renal dysfunction
– RAS with angina
Acute HPTN issues
– RAS with recurrent flash pulmonary edema
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
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
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
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
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
RAS and Hypertension alone
•
•
•
•
Treatment is empiric
Expectation of clinical improvement is less
Unilateral vs. Bilateral RAS
Hypertension response is poorly predictable
Hypertension with Renal Insufficiency
• 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
All patients
Hypertension with Renal Insufficiency
Hypertension with Renal Insufficiency
Hypertension with Renal Insufficiency
• 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
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
Options for Intervention
• 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
• Surgical Revascularization
– Ex-vivo reconstruction
• To be considered in:
–Solitary kidney
–Complex renal artery branch reconstructions
Options for Intervention
• Percutaneous Treatment
– Renal artery angioplasty
– Renal artery angioplasty with provisional/selective
stenting
– Renal artery stenting
• 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
• 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
Randomized
Trials
Percutaneous Renal Artery Intervention
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•
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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
• 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
• 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
• 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
• 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
• 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
The Big Hurt
• 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.
• 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
• 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
The Cardiovascular Outcomes with Renal Atherosclerotic
Lesions (CORAL) Study: Rationale and Methods
Timothy 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
Still not in publication
Treatment Recommendations
• Medical Therapy
Treatment Recommendations
• Interventional Therapy
Treatment Recommendations
• Interventional Therapy
Treatment Recommendations
• Interventional Therapy
Treatment Recommendations
• Interventional Therapy
Treatment Recommendations
• Interventional Therapy
Treatment Recommendations
• Surgical Therapy
Treatment Recommendations
• Surgical Therapy
Summary
Renal Revascularization
• Sound concept to treat a serious problem
• Basic science observations and observational
studies support its role in treating RAS
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
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
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
Thank You
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