RENAL VASCULAR DISEASES

SIGNIFICANCE
The prevalence and incidence of chronic kidney
disease (CKD) are increasing.
ESRD incidente patients rates are 168 in Canada,
1 250 in the USA and 85.7 in Romania.
It is of importance to search for reversible causes
of CKD.
Renal artery stenosis (RAS) may account for 5
22% of patients with ESRD who are older than 50
years;
Correction of ischemic lesions can reverse
decrease in renal function and improve CV
outcomes.

DEFINITION (K/DOQI)
Renal artery disease (RAD) is defined as a
stenosis of the main renal artery or its proximal
branches.
Significant RAD
anatomically if there is a >50% stenosis of the lumen
hemodynamically if the stenosis exceeds 75%.
clinically significant stenosis

RVHT - systemic hypertension due to

hemodynamically significant RAD.
Ischemic nephropathy
decreased GFR due to hemodynamically significant
RAD (K/DOQI)
impairment of renal function beyond occlusive disease
of the main renal arteries (Textor).

PREVALENCE (1)
RAS due to:
Atherosclerotic renovascular disease (ARVD >90%)
Fibromuscular disease (FMD).
Takayashus arteritis up to 60% (Indian subcontinent
and the Far East)

autopsy studies,
- 450% of subjects, (16.4 vs. 5.5% > 60 vs < 60 years)
aortic angiography,
- 38% of patients with aortic aneurysm,
- 33% in those with aortic occlusive disease
- 39% lower limb occlusive disease.
cardiac catheterization
- 1429% prevalence in coronary disease
- < 10% in normal coronary arteries .

PATHOGENY (1)
ARVD is associated with three major clinical
syndromes:
ischemic renal disease
hypertension.
Renal failure (acute and chronic)

PATHOGENY (2)

Interrelation among Renal-Artery Stenosis, Hypertension, and Chronic Renal Failure

Robert D. Safian, M.D., and Stephen C. Textor, M.D NEJM, Nr 6, vol 344:431-442,
2001

RAS AND KIDNEY FUNCTION (1)

27% of those with RAS develop chronic renal failure within 6 years.

Nephrol Dial Transplant (2007) 22: 10021006; Atherosclerotic renovascular

disease: beyond the renal artery stenosis; Pascal Meier, Jerome Rossert,
Pierre-Francois Plouin ,Michel Burnier

ISCHAEMIC NEPHROPATHY

(1)

Interstitial fibrosis,
tubular atrophy,
glomerulosclerosis (including focal segmental
glomerulosclerosis),
periglomerular fibrosis
arteriolar abnormalities (hialinosclerosis,
atheroembolism).
atherosclerotic nephropathy

ISCHAEMIC NEPHROPATHY (2)

Histologic studies of interstitial fibrosis (Trichrome stain, left two (a) low magnification and high magnification (b) and
immunohistochemistry for NF-kappa-B (NFkB, right) in swine. The presence of renal artery stenosis (RAS) induces both
interstitial fibrosis and NFkB), which is accelerated by the presence of high cholesterol levels (HC). (Chade AR,
Rodriguez-Porcel M, Grande JP, Krier JD, Lerman A, Romero JC, Napoli C, Lerman LO: Distinct renal injury in early
atherosclerosis and renovascular disease. Circulation 106: 11651171, 2002)

ISCHAEMIC NEPHROPATHY

(3)

Acute renal failure

bilateral renal arterial occlusion (RAO)
intra-renal cholesterol atheroembolization
damage from radiocontrast agents during intraarterial angiography
hypovolaemia, often with concurrent diuretic use
concurrent use of angiotensin-converting enzyme
inhibitors (ACE-I) or angiotensin II receptor blockers
(AII-RBs).

MARKERS OF PROGRESSION (1)

Lack of a relationship between RAS severity and renal
dysfunction
Renal parenchymal damage is the major factor
responsible for renal function loss in atherosclerotic renal
disease
Surrogate markers of progression:
decrease in renal artery diameter
decline in GFR
renal atrophy
proteinuria
From the data available, the best predictor of
progression to ESRD may be
GFR at presentation
and/or biopsy proven renal fibrosis score.

ARVD AND ITS ASSOCIATION WITH

HEART AND OTHER VASCULAR
DISEASES (1)
Coronary artery disease
RAS is associated with more severe and extensive
coronary artery disease
? effects of renal ischemia or is a marker for advanced
atherosclerosis and cardiovascular risk?
Wollenweber et al described a 6-year cardiovascular
eventfree survival of 53%, with risk related to the
severity of the renal stenosis.

ARVD AND ITS ASSOCIATION WITH

HEART AND OTHER VASCULAR
DISEASES (2)
Cardiac dysfunction including flash pulmonary oedema
presenting clinical syndrome in 41% of patients with
bilateral ARAS and in 12% of patients with unilateral ARAS.
angiotensin II promoted sodium retention and increase in
pulmonary microcirculation permeability
ARVD patients were found to have significantly higher
prevalence
left ventricular hypertrophy (78.5% compared with
46.0%)
left ventricular diastolic dysfunction (40.5% compared
with 12.0%),
greater left ventricular mass index (183 74 g/m2
compared with 116 33 g/m2).

ARVD AND ITS ASSOCIATION WITH

HEART AND OTHER VASCULAR
DISEASES (3)
Aortic aneurysm and peripheral vascular disease
Prevalence of ARVD in patients undergoing aortography
for intermittent claudication varying from 33%, 39%,
44.9%;
Cerebrovascular disease
The coexistence of ARVD in patients who have stroke
and/or carotid stenoses In an autopsy series of 346
cases of brain infarcts >75% RAS was found in 10.4%
of subjects and carotid artery stenosis in 33.6%.
Patients with carotid stenosis were more likely to have
ARVD than those without carotid disease.
Conversely, ARVD patients are more likely to have
carotid disease.

ARVD AND ITS ASSOCIATION WITH

HEART AND OTHER VASCULAR
DISEASES (4)
ARVD and hypertension
ARVD is found in 25% of all cases of hypertension
90% of patients with ARVD are hypertensive.
hypertension precedes ARVD development in many
cases.

DIAGNOSIS OF ARVD (1)

Clinical features suggestive of renovascular disease
Hypertension
Abrupt onset of hypertension in patients aged <30 years (suggestive of
FMD) or >50 years (suggestive of ARVD)
Absent family history of hypertension
Accelerated or malignant hypertension
Resistance to therapy (3 drugs)
Hypertension may be absent, particularly in patients with chronic
cardiac disfunction.

Renal abnormalities
Unexplained renal failure in patients aged >50 years
Elevation in plasma creatinine level after the initiation of ACE-I or AII-RB
therapy (> 30% increase in serum creatinine)
Asymmetrical kidneys on imaging

DIAGNOSIS OF ARVD (2)

Other
Unexplained acute pulmonary oedema or
congestive cardiac failure
Femoral, renal, aortic or carotid bruits
Severe retinopathy
History of extra-renal vascular disease
Hypokalaemia
Neurofibromatosis

DIAGNOSIS OF ARVD (3)

DRASTIC
The most powerful predictors for detecting lesions of
at least 50%:
age,
symptomatic vascular disease,
elevated cholesterol
the presence of an abdominal bruit.

DIAGNOSIS OF ARVD (4)

Investigation of ARVD
Duplex ultrasonography
widely available, noninvasive, and inexpensive.
First line screening test
sensitivity of 85% and specificity of 92%.
peak systolic velocity, has the highest performance
characteristics;
(Comparative Accuracy of Renal Duplex Sonographic
Parameters in the Diagnosis of Renal Artery Stenosis:
Paired and Unpaired Analysis; Gabrielle J. Williams;
AJR:188, March 2007; 1,357 titles, 88 studies involving
9,974 arteries in 8,147 patients)

DIAGNOSIS OF ARVD (5)

RI 80 cannot be recommended as the predictive
parameter of choice for the outcome of intervention in
patients with significant unilateral RAS. (Radermarker 2001
vs. Zeller T, Muller C, Frank U et al. Stent angioplasty of severe
atherosclerotic ostial renal artery stenosis in patients with diabetes
mellitus and nephrosclerosis. Catheter Cardiovasc Intervent 2003and
Garcia-Criado A, Gilabert R, Nicolau C et al. Value of Doppler
sonography for predicting clinical outcome after renal artery
revascularization in atherosclerotic renal artery stenosis. J Ultrasound
Med 2005 ;)

DIAGNOSIS OF ARVD (6)

Magnetic resonance imaging
the favoured imaging method for the proximal renal vasculature
The sensitivity ranges from 83% to 100% and specificity from 92% to
97%.
Gadolinium is non-nephrotoxic at low doses;

MR renal angiogram showing tight stenosis of the right renal artery and occlusion of the left
renal artery

DIAGNOSIS OF ARVD (7)

Computed tomography angiography
Sensitivity and specificity of 95%
Best for aortorenal calcification (utility in stent
placement);
Visualise main and accesory renal arteries.
Limitations
risk of contrast nephropathy
poor visualization of the distal main renal
artery and segmental branches.

DIAGNOSIS OF ARVD (8)

Renal scintigraphy and measurement of individual

kidney function
the captopril test unravel the degree of renin activation
Asymmetric result of a functional test RAS
Sensitivity and specificity variable: 43% - 93%
Insufficient sensitivity in:
Renal failure;
Renin independent hypertension

DIAGNOSIS OF ARVD (9)

Renal Arteriography
the gold standard diagnostic test. ?
risks of contrast nephropathy and
atheroembolic renal disease

DIAGNOSIS OF ARVD (10)

Conclusion
Computed tomographic angiography and
gadolinium enhanced magnetic resonance
angiography have the best diagnostic accuracies
for detecting renal stenosis.
(metaanalysis by Vasbinder et al/ 2001/ 5 studies on CTA,
16 on MRA, 24 on ultrasonography, 14 on captopril renal
scintigraphy)

Suggested work-up for RVHT

Marc A. Pohl

TREATMENT OPTIONS IN ARVD (1)

Few topics provoke more controversy between

nephrologists and interventional cardiologists
than management of atherosclerotic renovascular
disease

TREATMENT OPTIONS IN ARVD (2)

Medical treatment
Limiting the progression of atheromatous disease
and chronic kidney disease

vigorous control of hypertension and hyperlipidemia,

diabetes control
use of antiplatelet agents,
cessation of smoking
lifestyle modification (including reduced dietary intake
of salt and increased exercise).
attention to the complications of renal insufficiency

TREATMENT OPTIONS IN ARVD (3)

CORAL study (Cardiovascular Outcomes in Renal Atherosclerotic
Lesions)

TREATMENT OPTIONS IN ARVD (4)

Antihypertensive therapy
Is there an ideal blood pressure target that confers
maximal cardiovascular protection?
In CORAL, the target blood pressure is 140/ 90 mm
Hg ; 130/80 mm Hg is recommended for patients
with hypertension and diabetes or renal disease.
Is there a specific antihypertensive regimen that
provides cardiovascular benefits beyond just lowering
blood pressure?

TREATMENT OPTIONS IN ARVD (5)

First-line agent
Angiotensin receptor antagonist
First-line agent if ARB not tolerated - ACE inhibitor
especially for those
with proteinuric chronic parenchymal disease,
and those with coexisting coronary artery disease and
cardiac dysfunction.

Second-line agent
Thiazide diuretic
Combinations with ARB/ACE may be available
Use loop diuretics for patients with serum creatinine 2 mg/dL

Third-line agents (function of comorbidities)

Calcium channel blocker

Beta Blocker
Alfa Blocker
Vasodilator

TREATMENT OPTIONS IN ARVD (6)

Dyslipidemia Treatment
in terms of cardiovascular risk RAS is considered a
coronary artery disease equivalent. Third Report of the
Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults (Adult Treatment Panel III)

Goal of therapy
low-density lipoprotein cholesterol <100 mg/dL
some suggesting a target of < 70 mg/dL
Statins
effects independent of lipid-lowering
stabilize, slow progression or even induce regression of
atherosclerotic plaque
reduction of proteinuria

TREATMENT OPTIONS IN ARVD (7)

Diabetes Mellitus
HbA1c of <7 mg/dL with oral agents and/or insulin
medical nutrition therapy;
physical activity;
multidisciplinary foot and eye care;
Chronic Renal Insufficiency
Tight control of blood pressure, dyslipidemia, diabetes;
manage anemia; hyperparathyroidism. (Guidelines)
Antiplatelet Agents
Although there are no direct data in patients with RAS,
administration of an antiplatelet agent is required in
CORAL and recommended for all patients with RAS.
Aspirin, Clopidogrel or Ticlopidin.

TREATMENT OPTIONS IN ARVD (8)

Effect of the Medical Therapy Intervention

reduce cardiovascular risk
progression to end-stage renal disease actually
does not respond very well to medical therapy

TREATMENT OPTIONS IN ARVD (9)

Surgical treatment
revascularization
nephrectomy of small kidneys with relatively complete
arterial occlusion.

TREATMENT OPTIONS IN ARVD (9)

Evidence for renal revascularization
Randomized Trials in Renal Artery Stenosis Intervention
Year
Weibull
1993
Plouin
1998
Webster
1998
van de Ven 1999
van Jaarsveld 2000

n Medical Balloon
58
X
49
X
55
X
84
X
106
X

Stent End Points

X
BP/renal function
X
BP
X
BP/renal function
X
Patency/BP/renal function
X
BP/renal function

Benefits:
A modest improvement in blood pressure control
no improvement in renal function.

TREATMENT OPTIONS IN ARVD (10)

Definite indications for renal revascularization

Recurrent flash pulmonary oedema
Severe hypertension resistant to all medical therapy.
When a patient who requires ACE-I or AII-RB
therapy (e.g. for cardiac failure) presents with
significant ACE-I-related uraemia.
RAO in a reasonably sized kidney

TREATMENT OPTIONS IN ARVD (11)

CONTROVERSIES
Effect of Revascularization on Blood Pressure
Revascularization may fail to cure hypertension
In long-standing hypertension, secondary processes
that sustain hypertension
Vascular remodeling,
atherosclerosis,
ischemic damage to the poststenotic kidney,
hypertensive injury to the nonstenotic kidney

TREATMENT OPTIONS IN ARVD (12)

Effect of Revascularization on kidney function

filtration rate often fails to improve significantly after

revascularization
Intrinsic kidney damage rather than the vascular stenosis
per se accounts for the renal functional impairment.
Ongoing studies: Stenting in Renal Dysfunction Caused by
Atherosclerotic Renal Artery Stenosis (STAR) and
Angioplasty and Stent for Renal Artery Lesions (ASTRAL).
Effect of revascularisation on congestive heart failure (flush
pulmonary edema)

At present, there are no prospective randomized data

demonstrating that angioplasty and stenting reduce
admissions for severe congestive heart failure, or any other
cardiovascular event, compared with medical therapy.

PROGNOSIS OF PATIENTS WITH

ARVD (1)
Major mortality from cardiovascular complications; risk of
death is almost six times that of developing ESRD
Mailloux et al. showed that patients with ARVD receiving
dialysis had a median survival of 27 months and an
average 5-year survival of only 18%.
Fiveyear survival in two prospective studies was 7% lower
in patients with renal artery stenosis than in wellmatched
essential hypertensives and 23% lower than in the general
population (Wollenweber , Conlon et al.).

PROGNOSIS OF PATIENTS WITH

ARVD (2)

Kaplan-Meier survival plots for 491 patients with peripheral vascular

disease (PVD), comparing outcome for those without renal artery
stenosis (NRAS) and with renal stenosis

PROGNOSIS OF PATIENTS WITH

ARVD (3)

Time to renal replacement therapy or death according to

baseline GFR. (median survival 21 mo in those with
contralateral RAS <50%; Cheung.)