Download RENAL ARTERY STENOSIS

RENAL ARTERY STENOSIS
Grand Rounds
12/20/12
• 55 y.o Male with PMHx of hypertension, CKD stage III,
PVD s/p bilateral common iliac artery stent 5 years ago,
renal artery stenosis referred to vascular surgery from
WBVA for stenting of renal artery
• He started feeling intermittent burning sensation in his feet
and claudication after a walking a block Right>Left and
decided to go to his family PCP.
• PCP did basic lab work that showed cr of 3.7 and K of 5.8
(8/1/12) Lisinopril was d/ced and patient was referred to a
Nephrologist at the WBVA.
• Repeat lab work by the nephrologist showed cr of 1.9 after
lisinopril was d/ced. U/S abdomen was also performed
that revealed right renal artery stenosis, left occluded renal
artery and left small kidney
Physical Exam
• VS: BP 167/103 HR 64 T 98.4 SO2 100% on RA
• Gen: Middle aged male, NAD
• Resp: clear to auscultation b/l
• CVS: RRR, normal S1S2
• Abd: soft, nt, nd, bs positive
• LE: no edema,warm, non palpable DP/PT bilaterally
Meds:
Plavix 75 mg
Norvasc 5 mg qday
Atenolol 100 mg qday
Chlorthalidone 12.5 mg q day
Allergies: NKDA
Fhx: Mother with history of HTN and MI
Shx: h/o smoking 1PPD for 10 years. Occasional Etoh. No
IV drug abuse
Labs:
BMP:
Na 138 K 3.4 Cl 99 bicarb 32 BUN 27 Cr 1.8
Ca 10.1 phos 3.6 Mg 2.0
CBC: WBC 8.2 Hgb 16.5 plt 296
Lipid panel Chol 199 HDL 33 TG 231 LDL 119
UA
Protein neg, blood neg
Imaging
Renal Ultrasound: Right kidney 11.3 cm, right renal artery
stenosis. Left kidney 9.6 cm. Left renal artery occluded
MRA abdomen
There is atherosclerotic vascular disease of the abdominal
aorta. The origin of left renal artery is not demonstrated
with signal void from the artifact in the expected region of
the origin and proximal left renal artery which may
represent a stent, suggest clinical correlation. There is
severe focal stenosis in the right proximal renal artery
Introduction
• Atherosclerotic renal artery stenosis is a common problem
that is present in roughly 1% to 5% of the 60 million
Americans with hypertension and in a higher percentage
of patients with peripheral or coronary artery disease
• Recent date suggests that at least 7% of patients >65
years may have ARAS
…
• Vascular occlusive disease poses a threat to kidney
viability, but whether the events leading to injury and
fibrosis actually entail reduced oxygenation and regional
tissue ischemia is unknown
• Is there a method to assess tissue oxygenation in
humans?
Use of Magnetic Resonance to Evaluate Tissue
Oxygenation in Renal artery Stenosis
• BOLD (blood oxygen level dependent MRI detects changes in tissue
deoxyhemoglobin during manueuvers that affect oxygen consumption
• BOLD MRI was used to image and analyze cortical and medullary
segments of 50 kidneys in 25 subjects undergoing MRI angiography
to diagnose RAS
• Magnetic rate of relaxation (R2*)positively correlates with
deoxyhemoglobin levels and therefore used as a surrogate measure
of tissue oxygenation
• Lasix was administered to examine the effect of inhibiting energy
dependent electrolyte transport on tissue oxygenation
J Am Soc Nephrol 19:780-788, 2008
J Am Soc Nephrol 19:780-788, 2008
J Am Soc Nephrol 19:780-788, 2008
J Am Soc Nephrol 19:780-788, 2008
J Am Soc Nephrol 19:780-788, 2008
Revascularization with stenting vs Medical therapy ?
Stenting for atherosclerotic renal artery stenosis:
DRASTIC TRIAL: Dutch renal artery Stenosis Intervention
Cooperative trial
• 106 patients with renal artery stenosis and hypertension(
diastolic blood pressure >95 mm Hg) despite treatment with 2
antihypertensive medications were randomly assigned to either
renal angioplasty( n =56) or drug therapy ( n=50)
• Primary outcome measures were the systolic and diastolic
blood pressure at 3 months and 12 months after
randomization
• Secondary outcome measures were the numbers and defined
daily doses of antihypertensive drugs, the serum creatinine,
the creatinine clearance according to Cockcroft and Gault
N Engl J Med 2000:342:1007-1014
23 had at least
50% stenosis
N Engl J Med 2000:342:1007-1014
5 had an increase in
the stenosis
(20%points or more)
16 had no change
4 had a regression of
stenosis
Progressed to total occlusion in
4 patients
DRASTIC
PROBLEMS
Sample size was insufficient
Balloon angioplasty without stenting was used
Renal artery stenosis was defined as greater than 50%
stenosis
22 of the 50 patients randomized to medical therapy
crossed over to the angioplasty group
STAR TRIAL- Stent Placement in patients with atherosclerotic
Renal artery Stenosis and Impaired Renal function
• 140 patients with a creatinine clearance of less than
80ml/min/1.73m2, renal artery stenosis greater than 50%,
and well controlled blood pressure were randomized to
either renal artery stenting plus medical therapy(n=64) or
medical therapy alone (n=76).
• The primary end point was worsening of renal function,
defined as a 20% or greater decrease in creatinine
clearance compared with baseline.
• Secondary end points were procedural complications,
changes in blood pressure, incidence of refractory or
malignant hypertension and pulmonary edema,
cardiovascular morbidity and mortality , and total mortality
Ann Intern Med. 2009; 150(12):840-848
Ann Intern Med. 2009; 150(12):840-848
Primary end point was reached in both the groups at a mean of 10 months
5/10 patients in the stent group had repeated angiography before reaching the end point-3 had no stenosis
1 had restenosis treated with stenting, 1 had restenosis treated with balloon angioplasty.
All had persistence of decline in renal function1 month after repeated angiography
Ann Intern Med. 2009; 150(12):840-848
Primary end point
Primary end point plus death
Ann Intern Med. 2009; 150(12):840-848
…
• Complications:
• 2 died of procedure related causes within 30 days after
stent placement
• 11 patients had hematoma at the puncture site.
• 2 had false aneurysm of the femoral artery
• Injury to the kidney or renal artery occurred in 5 patients
Ann Intern Med. 2009; 150(12):840-848
FLAWS
• Mild renal artery stenosis: 33% of the patients in the study had mild
stenosis(50 to 70%) and 12 (19%) of the 64 patients randomized to
stenting actually had stenosis of less than 50%
• More than half of the patients had unilateral disease
• Not all “stent” patients received stents- only 46 (72%) of the 64 patients
randomized to stenting actually received a stent, while 18 (28%) did not .
There were 2 technical failures and 12 patients should not have been
randomized because they had less than 50% stenosis on angiography
and thus were not stented. Yet all 64 patients were analyzed(by intention
to treat) in the stent group
• Like DRASTIC , this trial was underpowered
• High complication rates. The periprocedural complication and death rates
were much higher than in many other reports on renal artery stenting
ASTRAL TRIAL- Angioplasty and stenting for Renal
artery Lesions
• 806 patients with the atherosclerotic renal artery stenosis
were randomized to either stent based revascularization
combined with medical therapy or medical therapy alone
• The primary outcome measure was the change in renal
function over time as assessed by the mean slope of the
reciprocal of the serum creatinine
N Eng J Med 2009;361:1953-62
N Eng J Med 2009;361:1953-62
N Eng J Med 2009;361:1953-62
N Eng J Med 2009;361:1953-62
N Eng J Med 2009;361:1953-62
N Eng J Med 2009;361:1953-62
…
Complications of revascularization
• 38 periprocedural complications in 31 of 359 patients(9%) who
underwent revascularization
• 19 of these events were considered to be serious complications
• 1 Pulmonary edema
• 1 Myocardial infarction
• 5 Renal embolizations
• 4 Renal artery occlusions
• 4Renal artery perforations
• 1 Femoral artery aneurysm
• 3 Cholesterol embolism leading to peripheral gangrene and
amputations of toes or limbs
• 20% had an adverse event between 24 hours and 1 month after the
procedure- deaths(2), groin hematoma/hemorrhage (4), AKI (5)
N Eng J Med 2009;361:1953-62
ASTRAL
Author’s Conclusion “ We found substantial risks but no evidence of
clinical benefit from revascularization in patients with atherosclerotic
renovascular disease”
Despite size, flaws remain
• Selection bias. For patient to be enrolled, the treating physician had to
be undecided on whether the patient should undergo
revascularization or medical management alone
• Normal renal function at baseline. 25% of patients had normal renal
function. In addition significant number had unilateral disease and
41% had stenosis less than 70%
• There was no core laboratory to adjudicate the interpretation of the
imaging studies. The reason this is so important is that visual
assessment of the degree of stenosis on angiography is not accurate
and almost always overestimates the degree of stenosis
• High adverse event rate. Major adverse event rate in the first 24
hours was 9% whereas the usual rate is 2% or less
CORAL TRIAL- Cardiovascular Outcomes in Renal
Atherosclerotic Lesions
Will CORAL give us the answer?
• CORAL is a randomized clinical trial contrasting optimal medical
therapy alone to stenting with optimum medical therapy on a
composite cardiovascular and renal end point
• The primary end point is survival free of cardiovascular and renal
adverse events, defined as composite of cardiovascular or renal
death, stroke, myocardial infarction, hospitalization for congestive
heart failure, progressive renal insufficiency or need for permanent
renal replacement therapy.
• The secondary end points evaluate the effectiveness of
revascularization in important subgroups of patients and with respect
to all cause mortality, kidney function, renal artery patency,
microvascular renal function and blood pressure control
American Heart Journal volume 152, july 2006
Primary inclusion criteria are
1) An atherosclerotic renal stenosis of ≥60% with a 20mm
Hg systolic pressure gradient or ≥ 80% with no gradient
necessary and 2) systolic HTN of ≥ 155mm Hg on ≥ 2
antihypertensive medications
Study design
Optimal Medical therapy
• The first line drug will be an AII type I receptor antagonist,
•
•
•
•
•
candesartan, with an ACE inhibitor used as a substitute
for candesartan in candesartan intolerant subjects
If the ARB or ACE-I produce a significant increase in Cr,
then an alternative antihypertensive agent will be used
An algorithm for stepwise BP control will be used
There will be no limit on the number or class of additional
antihypertensive drugs that patients can receive in either
treatment arm
Consistent with JNC VII recommendations, the target BP
in patients without comorbidities will be <135/85mm Hg:
In patients with diabetes and/or proteinuria, a lower target
BP of <130/85 will be used
American Heart Journal volume 152, july 2006
Indications for stenting
American College of Cardiology/AHA guidelines on indications
for renal artery stenosis : Percutaneous revascularization is
reasonable for patients with hemodynamically significant renal
artery stenosis and
• Accelerated hypertension, resistant hypertension and
malignant hypertension
• progressive kidney disease
• recurrent Unexplained congestive heart failure or sudden
unexplained pulmonary edema
Thank You!