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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
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.
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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)
PATHOGENY (2)
ISCHAEMIC NEPHROPATHY
(1)
Interstitial fibrosis,
tubular atrophy,
glomerulosclerosis (including focal segmental
glomerulosclerosis),
periglomerular fibrosis
arteriolar abnormalities (hialinosclerosis,
atheroembolism).
atherosclerotic nephropathy
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 9
atherosclerosis and renovascular disease. Circulation 106: 11651171, 2002)
ISCHAEMIC NEPHROPATHY
(3)
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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
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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 of
at least 50%:
age,
symptomatic vascular disease,
elevated cholesterol
the presence of an abdominal bruit.
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MR renal angiogram showing tight stenosis of the right renal artery and occlusion of the left renal artery
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Second-line agent
Thiazide diuretic
Combinations with ARB/ACE may be available
Use loop diuretics for patients with serum creatinine 2 mg/dL
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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
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Surgical treatment
revascularization
nephrectomy of small kidneys with relatively complete
arterial occlusion.
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n Medical Balloon
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X
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X
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X
84
X
106
X
Benefits:
A modest improvement in blood pressure control
no improvement in renal function.
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NEPHROSCLEROSIS
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Definition
clinical syndrome characterized by longterm essential hypertension, hypertensive
retinopathy, left ventricular hypertrophy,
minimal proteinuria, and progressive renal
insufficiency
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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 angiotensinconverting 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 for
more than one third of patients on
hemodialysis.
Europe: 12% of new patients starting renal
replacement therapy
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Race
In black people, hypertensive
nephrosclerosis occurs earlier, is more
severe, 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 in
black people
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DIAGNOSIS
Lab Studies
(I)
Lab Studies
(II)
urine protein excretion of lower than 1 g/d;
in some patients a 24-hour urinary protein
excretion 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 nephrotic
range.
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Imaging Studies
echocardiogram to assess left ventricular size.
Renal imaging with either an ultrasound or an
intravenous pyelogram reveals that kidney size is usually
symmetric 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 renal
artery stenosis or reflux nephropathy
ECG typically shows left ventricular hypertrophy; the
sensitivity of ECG in helping to detect left ventricular
hypertrophy may be as low as 22%.
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TREATMENT (I)
ACE inhibitors
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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 ACE
inhibitors
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)
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 greater
than 170 mm Hg in the first 24 hours has been
an acceptable target.
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