Renal hypertension

Renovascular HT
Renoparenchimatous HT
Nephroangiosclerosis
HT - kidney relationship

 Renovascular hypertension
 Renoparenchimatous hypertension
 Nephroangiosclerosis
Atherosclerosis-kidney relationship
The problem
 According to WHO reports, 600 million people worldwide have an
excessively high blood pressure and 3 million deaths annually are due
to the consequences of hypertension.
 It is estimated that 50 million people in the USA alone suffer from
hypertension (systolic blood pressure 140 mm Hg and/or diastolic
blood pressure 90 mm Hg, or patients undergoing treatment).
 If all those with an isolated diastolic or isolated systolic increase in
blood pressure are also included, more than 50% of all US citizens
over the age of 65 have high blood pressure.
 In 85 to 90% of cases, essential or primary arterial hypertension is
involved.
 In 5 to 10 % of cases, the hypertension is due to renal causes, i.e. the
secondary effect of a bilateral renal parenchymal disease.
 Only 1 to 2% of high blood pressure cases are attributable to
potentially curable diseases.
Prevalence of various forms of HT
Prevalence of various forms of HT in the general population and in Specialized
Referral Clinics
Diagnosis General population, % Specialty Clinics, %
Essential 92-94 65-85
Renal hypertension
– Parenchimal 2-3 4-5
– Renovascular 1-2 5-15
Endocrine hypertension
– Primary aldosteronism 0.3 0.5-12
– Cushing’s syndrome <0.1 0.2
– Pheochromocytoma <0.1 0.2
– Oral contracetive-induced 0.5-1
Miscellaneous 0.2 1
! <40 yrs – secondary HT reppresents >50%
Renoparenchimatous HT
Renovascular HT
RVHT - Background
 Renovascular hypertension (RVHT) denotes the causal relationship
between anatomically evident arterial occlusive disease and elevated blood
pressure. The coexistence of renal arterial vascular (ie, renovascular)
disease and hypertension roughly defines this type of nonessential
hypertension.
 Since Goldblatt's seminal experiment in 1934, RVHT has become
increasingly recognized as an important cause of clinically atypical
hypertension and chronic renal failure, the latter by virtue of renal ischemia.
 RVHT is the clinical consequence of renin-angiotensin-aldosterone
activation.
– As demonstrated by Goldblatt, renal artery occlusion creates ischemia, which
triggers the release of renin and a secondary elevation in blood pressure.
– Hyperreninemia promotes conversion of angiotensin I to angiotensin II, causing
severe vasoconstriction and aldosterone release.
– The ensuing cascade of events varies, depending on the presence of a
functioning contralateral kidney.
 Juxtaglomerular apparatus
 The juxtaglomerular apparatus is a small
endocrine organ associated with individual
nephrons within the kidneys. It is composed
of:
– the macula densa of the proximal distal tubule
of the nephron
– the closely situated afferent arteriole of the
same nephron
– 2 cell types intervening between macula densa
and arteriole in the 'mesangial' region:
 granular mesangial cells containing prorenin
granules, the precusor of renin; they are modified
smooth muscle cells which secrete renin into the
afferent arteriole
 agranular lacis cells
 sympathetic nerves lying in close proximity to
the granular cells
 The JGA is in an ideal position to monitor the
amount and composition of urine in the
nephron and blood in the afferent arteriole.
Renin secretion may be modified
accordingly.
RVHT - Pathophysiology
 The chief pathophysiologic mechanism underlying RVHT involves
activation of both limbs of the renin-angiotensin-aldosterone system
and depends on the presence or absence of a contralateral kidney.
 Unilateral renal ischemia initiates hypersecretion of renin, which
accelerates conversion of angiotensin I to angiotensin II and enhances
adrenal release of aldosterone. The result is profound angiotensin-
mediated vasoconstriction and aldosterone-induced sodium and water
retention.
 The sympathetic nervous system does not appear to play a role in
perpetuating elevated blood pressure in the 2-kidney 1-clip model of
RVHT. Evidence for a role in the 1-kidney 1-clip model of RVHT has
been presented but is not clear or definitive.
RVHT - Pathophysiology

Kidney ischaemia

Renin

Angiotensinogen Angiotensin I
ACE

Angiotensin II

Vasoconstriction Aldosteron

Natrium retention

Natriuresis

HBP
RVHT - Pathophysiology
RVHT - Causes
– Overall
 approximately 2/3 of RVHT cases are caused by atherosclerotic
disease and
 1/3 are caused by fibromuscular dysplasia or other congenital
disorders.
– Other clinical entities that may be associated with RVHT include
 cholesterol embolic disease
 acute arterial thrombosis or embolism
 aortic dissection
 renal arterial trauma
 arterial aneurysm
 arteriovenous malformation of the renal artery
 and polyarteritis nodosa
Classification of renal artery disease

Classification of renal artery disease

Disease Incidence, %
Atherosclerosis 60-80
Fibrous dysplasia 20-40
 Medial 30
 Perimedial 5
 Intimal 5
Atherosclerosis
Fibrous dysplasia
Perimedial fibroplasia.
– Selective right renal arteriogram
shows a tight stenosis in the mid
portion of the renal artery with a
small string of beads appearance,
typical of perimedial fibroplasia.
Medial fibroplasia
– Right renal arteriogram
demonstrates weblike stenosis
with interposed segments of
dilatation (large beads) typical of
medial fibroplasia (“string of
beads” lesion).
Intimal fibroplasia
– Selective right renal arteriogram
demonstrates a localized, highly
stenotic, smooth lesion involving
the distal renal artery, from intimal
fibroplasia.
Differential diagnosis
Atherosclerotic Medial fibroplasia
Men and women Women
Age >50–55 y Age 20–40 y
Total occlusion common Total occlusion rare
Ischemic atrophy common Ischemic atrophy rare
Surgical intervention or angioplasty: Surgical intervention or angioplasty:
- Mediocre cure rates of the hypertension - Good cure rates of the hypertension
- Less amenable to PTCA - More amenable to PTCA
RVHT - Clinical
 In adults, renovascular disease tends to appear at different times and
affects the sexes differently. Atherosclerotic disease affects mainly the
proximal third of the main renal artery and is most common among
older men. Fibromuscular dysplasia involves the distal two thirds and
branches of the renal arteries and is most common among younger
women.
 Frequency:
– In the US: RVHT is the most common type of secondary hypertension,
accounting for 1-5% of cases in unselected populations and as many as
30% of cases in selected populations. The prevalence may be up to 60% in
patients older than age 70 years.
– Internationally: The prevalence of RVHT internationally is not clear, but it
likely accounts for the sole etiology in a similarly small percentage (<1% in
the United States) of unselected patients with hypertension.
RVHT - Clinical
 Mortality/Morbidity
– In patients with hypertension, the presence of atherosclerotic renal artery disease is a
strong predictor of increased mortality relative to the general population.
– RVHT in the setting of renal dysfunction is associated with the greatest mortality.
 Race
– RVHT and renal artery stenosis, in particular, is less common among the black
population than the white population.
 Sex
– RVHT is most common in younger women and older men.
– Younger women develop RVHT most commonly from fibromuscular dysplasia
affecting the distal two thirds and branches of the renal arteries.
– Older men develop RVHT most often from atherosclerotic disease affecting mainly
the proximal third of the main renal artery.
 Age
– The onset of RVHT tends to occur in patients younger than 30 years or older than 50
years.
RVHT – Clue factors
 A history of hypertension with azotemia (serum creatinine level >1.5 mg/dL) and modest
proteinuria (levels <1.5 g/d) or progressive renal insufficiency,
 Accelerated or malignant hypertension,
 Severe hypertension (diastolic blood pressure >120 mm Hg),
 Hypertension with an asymmetric kidney,
 Paradoxical worsening of hypertension with diuretic therapy, and
 Hypertension refractory to standard therapy.
 Onset of hypertension occurring in patients younger than 30 years or older than 50 years
(may be abrupt)
 Abrupt onset of hypertension
 Severe or resistant hypertension
 Symptoms of atherosclerotic disease elsewhere
 Negative family history for hypertension
 Smoking tobacco products
 Azotemia with ACE inhibition
 Unprovoked hypokalemia (serum potassium level <3.6 mEq/L, often associated with
metabolic alkalosis)
 Recurrent pulmonary edema
RVHT - Physical
 Findings suggestive of long-standing hypertension may or may
not be evident upon physical examination.
– Recurrent flash pulmonary edema or unexplained episodes of
congestive heart failure
– Advanced funduscopic changes
– Abdominal bruit
 A clear abdominal bruit is heard in 46% of patients with RVHT.
 It also is heard in 9% of patients with essential hypertension; however,
innocent bruits are common in younger individuals.
 Systolic-diastolic bruits in combination with hypertension are
suggestive of RVHT.
RVHT - Differentials

 Other Problems to be Considered:

– Other nonessential forms of hypertension
– Essential hypertension
High blood pressure

1. Urinalysis
2. Renal function – blood creatinin, urea
3. Serum ionogram
4. ECG
5. Rx CP
6. Glycemia
7. Cholesterol, lipidis
8. Funduscopy
RVHT – specific screening tests
 Captopril test
 Plasma renin activity
 Renal vein renin measurements
 The IV pyelogram is mentioned as a test of historical
significance. Major findings on IV pyelography that suggest the
presence of unilateral ischemia include decreased renal size
and delayed caliceal appearance time when compared to the
contralateral kidney.
1. Kidney size asymmetry (>1.5 cm in long axis)
2. Irregularities of kidney contour
3. Indentation on pelvis/upper ureterus
4. Nephrographic asymmetry on ealy films
5. Pielographic asymmetry on late films (urographie trop belle)
6. Asymmetry of washout test
RVHT - Imaging Studies
 Renogram and captopril renogram
– Because of its high false-negative rate (20-25%), the
nonstimulated renal scan has limited efficacy as a screening
test.
– The predictive value of radioisotope scanning, however, can
be enhanced by the administration of captopril orally (25-50
mg) 1 hour before the isotope is injected. Positive results
from ACE inhibitor renogram are determined by the following
3 criteria:
1. decreased relative uptake of isotope, with 1 kidney accounting
for less than 40% of the total GFR and
2. delayed peak uptake of the isotope of more than 10-11 minutes
(normal is 3-6 min)
3. a slower washout of the isotope
RVHT - Imaging Studies

 Angiography
– Conventional renal angiogram or Intraarterial digital
subtraction angiogram (DSA) remains the current
diagnostic golden standard test for detecting renal artery
occlusive disease.
– Intravenous DSA is less invasive but requires more
radiocontrast than intraarterial DSA.
– Carbon dioxide digital angiography
RVHT - Imaging Studies
 Magnetic resonance angiography (MRA)
 Spiral CT scan with angiography
 Doppler ultrasonography
HTRV - Diagnosis
 Steps in making the diagnosis of renovascular
hypertension
1. Identification of clinical clues
2. Demonstration of renal arterial stenosis by angiography
3. Determination of pathophysiologic significance of the
stenotic lesion
4. Cure of the hypertension by intervention, ie,
1. revascularization,
2. percutaneous transluminal angioplasty,
3. nephrectomy
HTRV - Diagnosis
1. Identification of clinical clues
– At present, no sufficiently accurate, noninvasive, radiologic, or
serologic screening test is available that, if negative, completely
excludes the presence of RAS. Therefore, clinical index of
suspicion remains the primary determinant for the degree of
evaluation.
2. Demonstration of renal arterial stenosis by angiography
– When the history is highly suggestive and no risk for
radiocontrast-mediated renal injury is present, an intraarterial DSA
or conventional angiogram (criterion standard) is the appropriate
initial test. In patients at risk, a carbon dioxide angiogram can
determine the presence of a stenosis, and the risk of radiocontrast
angiogram is imposed only on those individuals most likely to
benefit.
– Perform a spiral CT scan, MRA, or duplex ultrasonography
(depending on availability and local experience) when moderate
suspicion of renovascular disease exists. A negative test result
indicates that an RAS is highly unlikely, while a positive test result
can be followed by renal arteriography
HTRV - Diagnosis
3. Determination of pathophysiologic significance of the stenotic
lesion
– Duration of hypertension <3–5 y
– Appearance of lesion on angiogram (>75% stenosis)
– Systolic-diastolic bruit in abdomen
– Renal vein renin ratio >1.5
– Positive captopril provocation test or captopril renogram
– Abnormal rapid sequence IVP
– Hypokalemia
Suggested work-up for RVHT

Marc A. Pohl
HTRV - Treatment
 Treatment options for renovascular hypertension and
ischemic nephropathy
– Pharmacologic antihypertensive therapy
– PTRA
– Renal artery stents
– Surgical renal revascularization
RVHT – Medical Treatment
 Medical Care:
– Antihypertensive drug therapy is indicated.
– Optimal blood pressure control plays an essential role in the therapeutic
management of RVHT; however, aggressive control of other risk factors for
atherosclerosis also is key.
– Cessation of smoking is important for its positive impact on the
cardiovascular risk profile in patients with hypertension. Similarly,
antidyslipidemic therapy for those patients with hyperlipidemia likely
provides benefit in atherosclerotic RVHT.
– Definitive therapy for the underlying cause must be considered in order to
avoid the development of ischemic nephropathy. Intervention of
hemodynamically significant stenoses has been presumed to offer clinical
benefit; however, trials comparing renal artery revascularization with
medical management do not unequivocally favor surgical over medical
intervention.
RVHT – Surgical treatment
 Percutaneous transluminal renal angioplasty
 Surgical revascularization
 Nephrectomy
RVHT – Follow-up
 Complications:
– Major complications of RVHT include end-organ damage from chronically
uncontrolled hypertension and progressive renal failure, an important and
indolent sequela of chronic renal ischemia.
 Prognosis:
– The prognosis of patients with RVHT is difficult to ascertain and varies with
the extent of the occlusive phenomena, the sensitivity of the individual to
antihypertensive therapy, and the efficacy of surgical repair and/or
angioplasty.
– RVHT in the setting of chronic renal ischemia and consequent renal
dysfunction has been linked to worse outcomes.
 Patient Education:
– Education about hypertension should include information about the clinical
features associated with RVHT (see Clinical) and information about the
importance of good blood pressure control.
RVHT - Conclusions
 Renal arterial atherosclerotic stenosis now is recognized as an
important and fastest-growing cause of end-stage renal disease.
Because preventing this form of renal failure is possible by performing
an operation or angioplasty, identifying patients who may be at risk for
renal ischemia by atherosclerosis is important. Even when renal
function is impaired, relief of the stenosis, if achieved early enough,
may result in dramatic improvement.
 A clinically atypical course of hypertension developing in people older
than 50 years, difficulty controlling long-standing hypertension that
previously was easy to control, or an increase in creatinine level after
administration of an ACE inhibitor all should be evaluated because
renal arterial disease may be present.
 Deterioration of renal function in the setting of diffuse atherosclerosis
but no proteinuria or known renal parenchymal disease, even in the
absence of hypertension, is highly suggestive of renovascular disease.