Renal Vascular Diseases Final

8/10/2019 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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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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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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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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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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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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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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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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Renal Arteriography

the gold standard diagnostic test. ? risks of contrast nephropathy andatheroembolic renal disease


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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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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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CORAL study (Cardiovascular Outcomes in Renal Atherosclerotic

Lesions)


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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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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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Diabetes Mellitus

HbA1c of


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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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Surgical treatment

revascularization nephrectomy of small kidneys with relatively complete

arterial occlusion.


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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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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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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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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.).



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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



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ARVD (3)

Time to renal replacement therapy or death according tobaseline GFR. (median survival 21 mo in those with

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Renal Vascular Diseases Final