renal vascular diseases final
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RENAL VASCULAR DISEASES
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SIGNIFICANCE
The prevalence and incidence of chronic kidneydisease (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 50years;
Correction of ischemic lesions can reversedecrease in renal function and improve CVoutcomes.
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DEFINITION (K/DOQI)
Renal artery disease (RAD) is defined as astenosis of the main renal artery or its proximalbranches.
Significant RAD anatomicallyif there is a >50% stenosis of the lumen
hemodynamicallyif the stenosis exceeds 75%. clinically significant stenosis
RVHT - systemic hypertension due tohemodynamically significant RAD.
Ischemic nephropathy decreased GFR due to hemodynamically significant
RAD (K/DOQI)
impairment of renal function beyond occlusive diseaseof the main renal arteries (Textor).
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PREVALENCE (1)
RAS due to:
Atherosclerotic renovascular disease (ARVD >90%)
Fibromuscular disease (FMD).
Takayashus arteritis up to 60% (Indian subcontinentand the Far East)
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autopsy stud ies,
- 450% of subjects, (16.4 vs. 5.5% > 60 vs < 60 years)
aort ic 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 .
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PATHOGENY (1)
ARVD is associated with three major clinical
syndromes:
ischemic renal disease
hypertension.
Renal failure (acute and chronic)
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PATHOGENY (2)
Interrelation among Renal-Artery Stenosis, Hypertension, and Chronic Renal Failure
Robert D. Safian, M.D., and Stephen C. Textor, M.DNEJM, Nr 6, vol 344:431-442,
2001
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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
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ISCHAEMIC NEPHROPATHY(1)
Interstitial fibrosis,
tubular atrophy,
glomerulosclerosis (including focal segmental
glomerulosclerosis),
periglomerular fibrosis
arteriolar abnormalities (hialinosclerosis,
atheroembolism).
atherosclerotic nephropathy
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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 earlyatherosclerosis and renovascular disease. Circulation106: 11651171, 2002)
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MARKERS OF PROGRESSION (1)
Lack of a relationship between RAS severity and renaldysfunction
Renal parenchymal damage is the major factorresponsible for renal function loss in atherosclerotic renaldisease
Surrogate markers of progression:
decrease in renal artery diameter
decline in GFR
renal atrophy
proteinuriaFrom the data available, the best predictor ofprogression to ESRD may be
GFR at presentation
and/or biopsy proven renal fibrosis score.
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ARVD AND ITS ASSOCIATION WITH
HEART AND OTHER VASCULAR
DISEASES (1)
Coronary artery dis ease
RAS is associated with more severe and extensivecoronary artery disease
? effects of renal ischemia or is a marker for advanced
atherosclerosis and cardiovascular risk?
Wollenweberet al described a 6-year cardiovasculareventfree survival of 53%, with risk related to the
severity of the renal stenosis.
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ARVD AND ITS ASSOCIATION WITH
HEART AND OTHER VASCULAR
DISEASES (2)Cardiac dysfunction including flash pulmonary oedema
presenting clinical syndrome in 41% of patients withbilateral ARAS and in 12% of patients with unilateral ARAS.
angiotensin II promoted sodium retention and increase inpulmonary microcirculation permeability
ARVD patients were found to have significantly higherprevalence
left ventricular hypertrophy (78.5% compared with46.0%)
left ventricular diastolic dysfunction (40.5% comparedwith 12.0%),
greater left ventricular mass index (183 74 g/m2compared with 116 33 g/m2).
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ARVD AND ITS ASSOCIATION WITH
HEART AND OTHER VASCULAR
DISEASES (3)Ao rt ic aneurysm and per ipheral vascular disease
Prevalence of ARVD in patients undergoing aortographyfor intermittent claudication varying from 33%, 39%,
44.9%;Cerebrovascu lar disease
The coexistence of ARVD in patients who have strokeand/or carotid stenoses In an autopsy series of 346cases 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 haveARVD than those without carotid disease.
Conversely, ARVD patients are more likely to have
carotid disease.
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ARVD AND ITS ASSOCIATION WITH
HEART AND OTHER VASCULARDISEASES (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.
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DIAGNOSIS OF ARVD (1)Clinical features suggestive of renovascular disease
Hypertension
Abrupt onset of hypertension in patients aged 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 abno rmali t ies 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
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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
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DIAGNOSIS OF ARVD (3)
DRASTIC
The most powerful predictors for detecting lesions ofat least 50%:
age,
symptomatic vascular disease,
elevated cholesterol the presence of an abdominal bruit.
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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. (Radermarker2001
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
Med2005;)
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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% to97%.
Gadolinium is non-nephrotoxic at low doses;
MR renal angiogram showing tight stenosis of the right renal artery and occlusion of the leftrenal artery
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DIAGNOSIS OF ARVD (7)
Computed tomography angiography
Sensitivity and specificity of 95%
Best for aortorenal calcification (utility in stentplacement);
Visualise main and accesory renal arteries.
Limitations
risk of contrast nephropathy poor visualization of the distal main renal
artery and segmental branches.
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DIAGNOSIS OF ARVD (8)
Renal scintigraphy and measurement of individualkidney 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
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DIAGNOSIS OF ARVD (9)
Renal Arteriography
the gold standard diagnostic test. ? risks of contrast nephropathy andatheroembolic renal disease
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DIAGNOSIS OF ARVD (10)
Conclusion
Computed tomographic angiography and
gadolinium enhanced magnetic resonanceangiography have the best diagnostic accuraciesfor detecting renal stenosis.
(metaanalysis by Vasbinder et al/ 2001/ 5 studies on CTA,
16 on MRA, 24 on ultrasonography, 14 on captopril renalscintigraphy)
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Suggested work-up for RVHT
Marc A. Pohl
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TREATMENT OPTIONS IN ARVD (1)
Few topics provoke more controversy between
nephrologists and interventional cardiologiststhan management of atherosclerotic renovascular
disease
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TREATMENT OPTIONS IN ARVD (2)
Medical treatment
Limiting the progression of atheromatous diseaseand chronic kidney disease
vigorous control of hypertension and hyperlipidemia,
diabetes control
use of antiplatelet agents,
cessation of smoking
lifestyle modification (including reduced dietary intakeof salt and increased exercise).
attention to the complications of renal insufficiency
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TREATMENT OPTIONS IN ARVD (3)
CORAL study (Cardiovascular Outcomes in Renal Atherosclerotic
Lesions)
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TREATMENT OPTIONS IN ARVD (4)
Antihypertensive therapy
Is there an ideal blood pressure targetthat confersmaximal cardiovascular protection?
In CORAL, the target blood pressure is 140/ 90 mmHg ; 130/80 mm Hg is recommended for patientswith hypertension and diabetes or renal disease.
Is there a specificantihypertensive regimenthatprovides cardiovascular benefits beyond just loweringblood pressure?
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TREATMENT OPTIONS IN ARVD (6)
Dyslipidemia Treatment in terms of cardiovascular risk RAS is considered a
coronary artery disease equivalent. Third Report of theExpert Panel on Detection, Evaluation, and Treatment of High BloodCholesterol in Adults (Adult Treatment Panel III)
Goal of therapy
low-density lipoprotein cholesterol
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TREATMENT OPTIONS IN ARVD (7)
Diabetes Mellitus
HbA1c of
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TREATMENT OPTIONS IN ARVD (8)
Effect of the Medical Therapy Intervention
reduce cardiovascular risk
progression to end-stage renal disease actuallydoes not respond very well to medical therapy
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TREATMENT OPTIONS IN ARVD (9)
Surgical treatment
revascularization nephrectomy of small kidneys with relatively complete
arterial occlusion.
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TREATMENT OPTIONS IN ARVD (9)
Evidence for renal revascularization
Randomized Trials in Renal Artery Stenosis Intervention
Year n Medical Balloon Stent End Points
Weibull 1993 58 X X BP/renal function
Plouin 1998 49 X X BP
Webster 1998 55 X X BP/renal function
van de Ven 1999 84 X X Patency/BP/renal function
van Jaarsveld 2000 106 X X BP/renal function
Benefits: A modest improvement in blood pressure control
no improvement in renal function.
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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
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TREATMENT OPTIONS IN ARVD (11)
CONTROVERSIES
Effect of Revascularization on Blood Pressure
Revascularization may fail to cure hypertension
In long-standing hypertension, secondary processesthat sustain hypertension
Vascular remodeling,
atherosclerosis, ischemic damage to the poststenotic kidney,
hypertensive injury to the nonstenotic kidney
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TREATMENT OPTIONS IN ARVD (12)
Effect of Revascularization on kidney function
filtration rate often fails to improve significantly afterrevascularization
Intrinsic kidney damage rather than the vascular stenosisper se accounts for the renal functional impairment.
Ongoing studies: Stenting in Renal Dysfunction Caused byAtherosclerotic Renal Artery Stenosis (STAR) andAngioplasty and Stent for Renal Artery Lesions (ASTRAL).
Effect of revascularisation on congestive heart failure (flushpulmonary edema)
At present, there are no prospective randomized datademonstrating that angioplasty and stenting reduceadmissions for severe congestive heart failure, or any othercardiovascular event, compared with medical therapy.
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PROGNOSIS OF PATIENTS WITH
ARVD (1)
Major mortality from cardiovascular complications; risk ofdeath is almost six times that of developing ESRD
Mailloux et al.showed that patients with ARVD receivingdialysis had a median survival of 27 months and anaverage 5-year survival of only 18%.
Fiveyear survival in two prospective studies was 7% lowerin patients with renal artery stenosis than in wellmatched
essential hypertensives and 23% lower than in the generalpopulation (Wollenweber , Conlon et al.).
PROGNOSIS OF PATIENTS WITH
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PROGNOSIS OF PATIENTS WITH
ARVD (2)
Kaplan-Meier survival plots for 491 patients with peripheral vasculardisease (PVD), comparing outcome for those without renal artery
stenosis (NRAS) and with renal stenosis
PROGNOSIS OF PATIENTS WITH
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PROGNOSIS OF PATIENTS WITH
ARVD (3)
Time to renal replacement therapy or death according tobaseline GFR. (median survival 21 mo in those with
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