Renal Vascular Diseases

8/21/2019 Renal Vascular Diseases

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RENAL VASCULAR DISEASES


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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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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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PREVALENCE

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 .


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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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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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Acu te renal fai lure

bilateral renal arterial occlusion (RAO)

intra-renal cholesterol atheroembolization damage from radiocontrast agents during intra-

arterial angiography

hypovolaemia, often with concurrent diuretic use

concurrent use of angiotensin-converting enzymeinhibitors (ACE-I) or angiotensin II receptor blockers(AII-RBs).


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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?


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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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Investigation of ARVDDuplex 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;


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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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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 AtheroscleroticLesions)


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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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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


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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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PROGNOSIS OF PATIENTS WITH

ARVD (1)

Major mortality from cardiovascular

complications; risk of death is almost sixtimes that of developing ESRD


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NEPHROSCLEROSIS


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Definition

clinical syndrome characterized by long-

term essential hypertension, hypertensive

retinopathy, left ventricular hypertrophy,

minimal proteinuria, and progressive renalinsufficiency


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Pathophysiology

glomerular ischemia:chronic hypertension

result in narrowing of preglomerular

arteries and arterioles, with a consequent

reduction in glomerular blood flow

Glomerulosclerosis induce by glomerular

hypertension and glomerular hyperfiltration


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Genetics

a significant loss in kidney function was

observed in black people despite similar

levels of BP control

polymorphism in the angiotensin-

converting enzyme (ACE) gene, the DD

genotype

increased angiotensinogen mutations


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Frequency

USA: 1985-2005, adjusted rates of ESRD

caused by hypertension increased 140%

Hypertensive nephrosclerosis accounts formore than one third of patients on

hemodialysis.

Europe: 12% of new patients starting renalreplacement therapy


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Race

In black people, hypertensive

nephrosclerosis occurs earlier, is moresevere, and more often causes ESRD

(36.8% in black patients vs 26% in white

patients).


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Age

The diagnosis of hypertensive

nephrosclerosis increases with advancing

age. The peak age for the development of

ESRD in white patients is 65 years and

older, while the peak age is 45-65 years inblack people


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DIAGNOSIS

Long-standing or very severe hypertension Black race

Hypertension preceding renal dysfunction

Hypertension diagnosed prior to the onset ofproteinuria

No evidence of another renal disease

Biopsy findings compatible with the diagnosis

Proteinuria less than 0.5 g/d

Hypertensive retinal changes

Left ventricular hypertrophy


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Lab Studies

(I)

Baseline complete blood cell count

Creatinine level

Electrolyte status Urinalysis

Either a spot urine test for albumin or

creatinine ratio or a 24-hour urinecollection - To determine total protein

excretion

S


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Lab Studies

(II)

urine protein excretion of lower than 1 g/d;

in some patients a 24-hour urinary proteinexcretion greater than 1 g/d has been

described. When secondary changes of focal

segmental glomerulosclerosis (FSGS)

related to hyperfiltration develop,proteinuria can increase to the nephroticrange.


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Imaging Studies

echocardiogram to assess left ventricular size.

Renal imaging with either an ultrasound or anintravenous pyelogram reveals that kidney size is usuallysymmetric and may be normal or modestly reduced.

The renal calices and pelves are normal. Renal asymmetry or irregularities in the contour raise the

possibility that hypertension could be secondary to renalartery stenosis or reflux nephropathy

ECG typically shows left ventricular hypertrophy; thesensitivity of ECG in helping to detect left ventricularhypertrophy may be as low as 22%.


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Histologic Findings(I)

medial and intimal thickening with intimal

fibrosis of preglomerular arterioles

hyalinosis of afferent arterioles

secondary tubular atrophy

interstitial fibrosis

malignant hypertension Fibrinoid necrosis

microinfarcts


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Histologic Findings (II)

GLOMERULAR CHANGES

Obsolescent glomeruli were defined as glomeruli in

which Bowman's space was occupied by collagenous,PAS positive material, and the tuft was retracted

Solidified glomeruli were defined as glomeruli in

which the entire tuft was solidified, in the absence of

the collagenous change in the capsular space

Disappearing glomeruli were identified as globally

sclerotic glomeruli where there was an absence or

partial disappearance of Bowman's capsule


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TREATMENT (I)


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TREATMENT (I) BP goal of less than 130/80 mm Hg to preserve renal function and to reduce

cardiovascular events in patients with hypertension and diabetes.

Lower BPs are recommended for patients with proteinuria greater than 1 g/d

and renal insufficiency, regardless of etiology

ACE inhibitors

Effects and indications

Reduce proteinuria

Specific renal protective effect both in diabetic and nondiabetic renal impairment

Reduce morbidity and mortality rates in congestive heart failure Monotherapy less effective in older patients (>50 y)

Larger doses required in black patients

Inhibit or blunt all adverse metabolic effects of thiazides

Dose reduction required in renal failure

Reduce left ventricular hypertrophy and thirst

Adverse effects Cough (approximately 10%)

Angioedema (rare)

Hyperkalemia (especially in renal tubular acidosis type IV)

GFR reduction in patients with impaired renal function

May precipitate acute renal failure in patients with renal artery stenosis

Interfere with breakdown of bradykinin

Contraindicated in pregnancy


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TREATMENT (II) Angiotensin II receptor antagonists

Effects and indications Reduce proteinuria

Indicated in patients intolerant of ACE inhibitors

Can be used in combination with an ACE inhibitor

Do not cause cough

Reduce left ventricular hypertrophy and thirst similarly to ACEinhibitors

Do not interfere with breakdown of bradykinin

Adverse effects

Hyperkalemia

May reduce GFR in patients with impaired renal function May precipitate acute renal failure in patient with renal artery

stenosis

Angioedema (rare)

Contraindicated in pregnancy

Data in black patients limited


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TREATMENT (III)

Calcium channel blockers Effects and indications

Effective as monotherapy in black patients and elderly patients

Potentiate ACE inhibitor effects

Renal protection not proven

Reduce morbidity and mortality rates in congestive heart failure Indicated in patients with diastolic dysfunction

No change in dose with renal failure

Adverse effects

Possible increase in cardiovascular mortality rate with short-actingdihydropyridines

Edema

Constipation (verapamil)

Profound bradycardia possible when verapamil and diltiazem usedin combination with a beta-blocker


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Malignant hypertension(1)

1% of patients with hypertension;

It may occur in patients with preexisting hypertension orin a previously normotensive patient

Systolic BP can range from 150-290 mm Hg while

diastolic BP can vary from 100-180 mm Hg. Keith-Wagener grade III (hemorrhages and exudates)

and grade IV retinal changes (papilledema) are thehallmarks of malignant hypertension.

Acute heart failure: pulmonary edema can be thepresenting signs in approximately 10% of patients.

Left ventricular hypertrophy is present in as many as75% of patients at presentation


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Malignant hypertension (2)

60% of patients complain of headaches

5-10% cerebrovascular event (eg, focalcerebral ischemia, cerebral/subarachnoid

hemorrhage) hypertensive encephalopathy is

characterized by headache, nausea,vomiting, and visual blurring, together withimpaired cognitive function, generalizedseizures, or cortical blindness.


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Malignant hypertension (3)

microangiopathic hemolytic anemia (schistocytes,thrombocytopenia, increased fibrin degradation products,and increased fibrinogen) is frequently present

Renal involvement is common, but the degree of

severity varies Proteinuria is common, but overt nephrotic syndrome is

unusual

30% of patients will have an elevated serum creatininelevel at presentation

Other symptoms include weakness, malaise, fatigue,and weight loss

TREATMENT OF MALIGNANT


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TREATMENT OF MALIGNANT

HYPERTENSION

Malignant hypertension complicated by organ

failure is a medical emergency and requires

rapid reduction in BP

In uncomplicated malignant hypertension, rapid

BP reduction is not as critical as in the previous

group with BP reduction by up to 20% of the

presenting values, or a systolic BP of greaterthan 170 mm Hg in the first 24 hours has been

an acceptable target.

Documents

Renal Vascular Diseases