Transcript Document

Evaluation and treatment
of renal hypertension
Dr.
Scope
 Renal hypertension
 Introduction
 Causes
 ARAS,





FMD
 Takayasu’s arteritis
Pathophysiology
Clinical features
Diagnosis
 Imaging
Management
Conclusions
Renovascular hypertension
(RVH)
 Renal Hypertension or RVH:


Defined as
 The presence of systemic hypertension due to a
stenotic or obstructive lesion within the renal
artery
Form of secondary hypertension, accounting for an
estimated 0.5% to 4% of cases in unselected
hypertensive patients
US Nephrology 2009;5(2):56–59,
Proc (Bayl Univ Med Cent) 2010;23(3):246–49
RVH: Introduction
 The simultaneous presence of renal artery
stenosis (RAS) and systemic hypertension
should not lead to the conclusion that
The patient has RVH;
Strictly speaking, the definitive diagnosis of RVH
can only be made retrospectively
 When hypertension improves upon correction of
the stenosis


US Nephrology 2009;5(2):56–59,
Proc (Bayl Univ Med Cent) 2010;23(3):246–49
RVH: Introduction (Contd)
 In practice, obtaining complete “reversal”
of hypertension is rarely possible

Important to recognize that renovascular
disease
 Often
accelerates preexisting hypertension,
 Can ultimately threaten the viability of the
post-stenotic kidney and
 Impair sodium excretion in subjects with
congestive heart failure
Med Clin North Am. 2009 May ; 93(3): 717,
available in PMC 2010 May 1.
RVH: Causes
The
two most common
causes of RVH are
1. Atherosclerotic renal
artery stenosis (ARAS)
2. Fibromuscular dysplasia
(FMD)
Med Clin North Am. 2009 May ; 93(3): 717,
available in PMC 2010 May 1.
RVH: Causes (Contd)
 Takayasu’s arteritis (TA)


Although TA has a worldwide distribution, it
is observed frequently in Asia than in North
America
The most common cause of RVH in
 India
 China
 Korea
 Japan
and other countries of South East Asia
Eur J Vasc Endovasc Surg 2007;33, 578-82
RVH: Indian studies
 TA


In one study from Chandigarh by Sharma
et al Takayasu’s arteritis was found as the
leading cause of hypertension in
hospitalised patients
Involvement: 50% cases bilateral and in
28% unilateral
 Indicating
that this condition must be kept in
mind as one of the important causes,
especially in northern India, whenever one is
considering RVH
Angiology 1985; 36: 370-8
RVH: Indian studies (Contd)
 Study at PGI Chandigarh

205 patients with hypertension were shown
to have a renovascular aetiology over 16
years. Of these,
 125
(61 %) Takayasu's arteritis,
 58 (28.3 %) fibromuscular dysplasia,
 16 (7.8 %) atherosclerosis,
 five (2.4 %) polyarteritis nodosa and
 one (0.5 %) renal artery aneurysm
Q J Med. 1992;85:833-43.
RVH: Indian studies (Contd)
 Study at PGI Chandigarh (Contd)
 Among patients with TA, males were affected as
commonly as females
 The mean age of these patients at the time of detection
was 26.8 +/- 8.6 years (range 5-52 years)



Type I arteritis in nine (7.2 %),
Type II in 40 (32 %) and
Type III in 76 (60.8 %) patients
 The abdominal aorta was involved in 117 (93.3 %)
patients

TA was associated with ulcerative colitis in two patients
and with renal amyloidosis and focal segmental
glomerulosclerosis with a nephrotic syndrome in one
patient each
Q J Med. 1992;85:833-43.
RVH: Indian studies (Contd)
 Seth GS Medical College & KEM
Hospital, Parel, Mumbai




Medical records of 54 patients with RVH
showed
Aortoarteritis 44 (81.5%),
Atherosclerotic disease 7 (31.5%) and
Fibromuscular dysplasia 3 (5.6%) as
etiologies of RVH
32nd Annual Conference of Indian
Society of Nephrology September, 2001
TA
 TA is a chronic vasculitis involving
mainly the aorta and its branches, as
well as the pulmonary and coronary
arteries
 Classical definition of TA is that of

Chronic, progressive, inflammatory,
occlusive disease of the aorta and its
branches
Eur J Vasc Endovasc Surg 2007;33, 578-82
TA: Aetiology
 Remains enigmatic
 Various mechanisms such as post-
infective, autoimmune, ethnic
susceptibility and a genetic
predisposition have been postulated
 Autoimmunity appears to be the most
plausible mechanism
Eur J Vasc Endovasc Surg 2007;33, 578-82
ARAS
 Most common and problematic cause of
RVH

90% of cases of RVH due to ARAS
 Mainly in older men
 Lesion at the ostium or proximal third of
the renal artery as an extension of an
aortic plaque
 Bilateral in approx. 1/3 of cases
Med Clin North Am. 2009 May ; 93(3): 717,
available in PMC 2010 May 1.
ARAS (Contd)
Aortogram demonstrating highgrade stenosis affecting the left
renal artery
Quantitative measurements
indicated more than 86% lumen
obstruction
Med Clin North Am. 2009 May ; 93(3): 717,
available in PMC 2010 May 1.
ARAS (Contd)
 Risk factors
 Identical to those associated with
systemic atherosclerosis, i.e.,




Advanced age, male sex, smoking,
Diabetes mellitus, hypertension,
Positive family history, and
Dyslipidemia
US Nephrology 2009;5(2):56–59,
Proc (Bayl Univ Med Cent) 2010;23(3):246–49
ARAS (Contd)
 Generally believed that


ARAS slowly progresses over time, but the
rate of progression is variable
Atherosclerotic renovascular disease is
associated with accelerated and more
severe target organ injury than essential
HT
HT- Hypertension
US Nephrology 2009;5(2):56–59,
Proc (Bayl Univ Med Cent) 2010;23(3):246–49
FMD
 10% of cases of RVH are due to FMD


Mainly in younger women
Bilateral renal artery involvement with
extension into the distal portion of the
artery and its branches is common
US Nephrology 2009;5(2):56–59,
Proc (Bayl Univ Med Cent) 2010;23(3):246–49
RVH: Pathophysiology
Safian & Textor. NEJM 344:6;
RVH: Pathophysiology (Contd)
 Widely believed that

The obstructing lesion in the renal artery
has to reach a “critical level” of about 75%
to cause any clinically significant
hemodynamic effects
US Nephrology 2009;5(2):56–59,
Proc (Bayl Univ Med Cent) 2010;23(3):246–49
RVH: Pathophysiology (Contd)
US Nephrology 2009;5(2):56–59,
Proc (Bayl Univ Med Cent) 2010;23(3):246–49
RVH: Pathophysiology (Contd)
 Bilateral RAS, or unilateral RAS in a
functionally impaired or absent
contralateral kidney,

The increased renin produced by both
kidneys is responsible for the increased
salt and water retention and subsequent
HT
US Nephrology 2009;5(2):56–59,
Proc (Bayl Univ Med Cent) 2010;23(3):246–49
RVH: Pathophysiology (Contd)
 Unilateral RAS with a normal
contralateral kidney,


HT is caused by the increased renin
produced in the ischemic kidney while
The nonischemic kidney has its renin
production suppressed
US Nephrology 2009;5(2):56–59,
Proc (Bayl Univ Med Cent) 2010;23(3):246–49
RVH: Diagnosis
 Mere presence of RAS and hypertension
does not establish the diagnosis of RVH
 Three-step approach to the diagnosis of
RVH has been suggested
Curr Cardiol Rep 2005;7(6):405–11.
RVH: Diagnosis (Contd)
 First step:

An appropriate selection of patients who
are more likely to have RVH
 Second step:
 The patients’ renal arteries are imaged to
demonstrate RAS
 Third step:

Resolution or improvement in blood
pressure control occurs with reversion of
the stenosis
Curr Cardiol Rep 2005;7(6):405–411.
RVH: Diagnosis (Contd)
 Clinical findings associated with RVH
N Engl J Med 2001;344(6):431–42.; Curr Cardiol Rep
2005;7(6):405–11; Kidney Int 2006;70(9):1543–1547
RVH: Diagnosis (Contd)
Clinical
findings associated with RVH
(Contd)
ACE: angiotensin-converting enzyme; ARBs: angiotensin II
receptor blockers; RAS: renal artery stenosis
N Engl J Med 2001;344(6):431–42.;
Curr Cardiol Rep 2005;7(6):405–11; Kidney Int 2006;70(9):1543–1547
RVH: Diagnosis (Contd)
 Clinical findings associated with RVH
(Contd)
AAA: abdominal aortic aneurysm;
CAD, coronary artery disease; PAD:peripheral arterial disease
N Engl J Med 2001;344(6):431–42.; Curr Cardiol Rep 2005;7(6):405–11;
Kidney Int 2006;70(9):1543–47
RVH: Imaging
 Intra-arterial angiography



The gold standard
Invasive and carries the risk of contrastinduced nephropathy
Not used routinely unless
 Concurrent
therapy with angioplasty,
with/without stenting, is being considered
RVH: Imaging (Contd)
 Digital subtraction angiography (DSA)


Uses less dye than a conventional
arteriogram but is still invasive
The quality of images with DSA is not as
good as with conventional angiogram
RVH: Imaging (Contd)
 Captopril-enhanced renography and
scintigraphy



Noninvasive test and the ability to assess
renal functional status
Use is limited in patients with bilateral RAS
and in patients with significant renal
insufficiency
Provide a basis for functional, not
anatomical, diagnosis of RAS, as there is
no direct visualization of the renal arteries
RVH: Imaging (Contd)
 Duplex ultrasound imaging


Direct visualization of the renal vascular
tree while assessing blood flow velocity
and pressure wave forms
Limitations include interoperator variability
and the need for expertise in obtaining and
interpreting the images
RVH: Imaging (Contd)
 Spiral computed tomography
angiography



Enables a three-dimensional
reconstruction of the vascular tree
Excellent sensitivity and specificity to
visualize RAS
However, requires up to 150 cc of
iodinated contrast, which may be
nephrotoxic
RVH: Imaging (Contd)
 Magnetic resonance angiography (MRA)



Noninvasive imaging technique and results in
excellent visualization of the renal vasculature
Gadolinium is used as the radio-contrast in the
phase contrast technique
Drawbacks
 High cost
 Potential for nephrogenic systemic fibrosis in
patients with renal insufficiency
TA: Diagnostic criteria
 Following table mentions

Sensitivity and specificity for the various
diagnostic criteria
Eur J Vasc Endovasc Surg 2007;33, 578-82
TA: Diagnostic
criteria
Modified diagnosis criteria
for TA: Sharma et al
Eur J Vasc Endovasc Surg 2007;33, 578-82
TA: Diagnostic
criteria (Contd)
Modified diagnosis criteria
for TA: Sharma et al
(Contd)
Eur J Vasc Endovasc Surg 2007;33, 578-82
TA: Diagnostic criteria (Contd)
 Type I is limited to the aortic arch and its
branches
 Type II affects the descending thoracic and
abdominal aorta
 Type III is extensive form involving the arch and
the thoracic and abdominal aorta
 Type IV is designated to those cases with
pulmonary involvement in addition to the
features of type I, II, or III
Eur J Vasc Endovasc Surg 2007;33, 578-82
TA: Clinical features
 TA classically progresses through 3
stages:



An early systemic illness usually
associated with constitutional symptoms
and fever
A vascular inflammatory phase
The inflammation settles down or burns out
Eur J Vasc Endovasc Surg 2007;33, 578-82
TA: Clinical features (Contd)
Eur J Vasc Endovasc Surg 2007;33, 578-82
RVH: Management
 Treatment options include



Pharmacological therapy with various
antihypertensive medications,
Percutaneous angioplasty with or without
stent placement, and
Surgical revision of RAS
RVH: Management (Contd)
 Availability of potent antihypertensive
drugs and the advances in endovascular
techniques, as well as stents, have
made surgical treatment rarely
necessary
RVH: Management (Contd)
RVH: TA Management
 Besides management of hypertension and its
complications,

Steroids and immunosuppressive agents like
methotrexate and cyclophosphamide are used to
suppress disease activity
 Response to therapy is faster and better in
children with a higher rate of remission
 Anti-platelet agents like aspirin and
dipyridamole have been used especially in
patients with transient neurological symptoms
Eur J Vasc Endovasc Surg 2007;33, 578-82
RVH: TA Management (Contd)
 Percutaneous transluminal angioplasty
(PCTA) is the commonest palliative
procedure performed with a success rate
varying from 56-80%

All lesions are not amenable to PCTA and
surgical bypass procedures become
imperative when stenosis exceeds 70%
Eur J Vasc Endovasc Surg 2007;33, 578-82
RVH: TA Management (Contd)
 Irrespective of the surgical procedures
undertaken, the outcome appears to be
favorable when the disease is quiescent
 Surgical procedures are required for total aortic
occlusion, severe aortic incompetence, critical
central nervous system ischemia, aneurysms,
renovascular hypertension, ostial lesions, tight
stenosis, extensive renal segmental artery
involvement, poorly functioning renal units,
renal failure and, occasionally, in case of failure
of angioplasty
Eur J Vasc Endovasc Surg 2007;33, 578-82
RVH: TA Management (Contd)
 Surgery for TA should be deferred in the active
phase of the disease, which is characterized by
an increased ESR, increased C-reactive protein
and symptoms of fever, malaise or pain over
the major arteries, or signs of progressive
vascular involvement on angiography as the
chances of thrombosis increase

Surgery is often difficult in the active disease period
due to more bleeding, friable tissue and the high
chance of thrombosis
Eur J Vasc Endovasc Surg 2007;33, 578-82
RVH: FMD Management
 FMD
 Percutaneous angioplasty is the treatment of
choice,

Often resulting in relief of the stenosis and marked
improvement (or cure) of the hypertension
 Stents may be used
 In patients with suboptimal results with angioplasty
alone
 Surgery is considered to be the last option,
particularly

For patients for whom endovascular procedures
have failed
RVH: FMD Case
CT angiogram obtained in a 45
y.o. woman presenting with new
onset RVH
Aneurysmal dilation and vascular
occlusion beyond a fibromuscular
lesion is present in the right
kidney associated with loss of
perfusion to the entire upper pole
of the kidney
 Antihypertensive therapy in this
instance can be achieved using
agents that block the RAS
 While such cases are unusual,
they underscore the broad range
of lesions that can produce the
syndrome of RVH
Fibromuscular Dysplasia, before
and after PTRA
Safian & Textor. NEJM 344:6;
Atherosclerotic RAS before and after stent
RVH: ARAS Management
 ARAS
 No general consensus among
physicians on the ideal therapy for this
condition

Numerous randomized prospective studies
have found no evidence of improvement in
BP control in patients undergoing
angioplasty over medical therapy alone
RVH: ARAS Management (Contd)
 One of the largest trials,

The Angioplasty and Stenting for Renal
Artery Lesions (ASTRAL) study,
 806
renal failure patients (mean serum
creatinine approximately 2 mg/dL) with
atherosclerotic renal vascular disease
included
 Randomized to receive either
revascularization and medical therapy or
medical therapy alone
N Engl J Med 2009;361(20):1953–1962
RVH: ARAS Management (Contd)
 ASTRAL Study


(Contd)
On average, patients had 75% RAS
At 1-year follow-up there were no
differences in the change in serum
creatinine level (it rose by 0.2 mg/dL in
both groups) or in rates of renal events,
including acute renal failure
N Engl J Med 2009;361(20):1953–1962
RVH: ARAS Management (Contd)
 Currently, at least three major studies
are under way to help decipher optimum
treatment for patients with ARAS



1. STAR
2. RAS-CAD
3. CORAL
RVH: ARAS Management (Contd)
 STAR study

The STent placement and blood pressure and lipidlowering for the prevention of progression of renal
dysfunction caused by Atherosclerotic ostial
stenosis of the Renal artery (STAR) study aims to
compare
 The effects of renal artery stent placement
together with medication versus medication alone
on renal function in 140 ARAS patients
 Medication consists of statins, antihypertensive
drugs, and antiplatelet therapy
Ann Intern Med 2009;150(12):840–848
RVH: ARAS Management (Contd)
 RAS-CAD
 A trial looking at cardiac endpoints, the stenting of
Renal Artery Stenosis in Coronary Artery Disease
(RAS-CAD),
 Randomized study aiming to recruit 168 patients
 Designed to study the effect of medical therapy
alone versus medical therapy plus renal artery
stenting on


left ventricular hypertrophy progression (primary
endpoint), and
cardiovascular morbidity and mortality (secondary
endpoints), in patients affected by ischemic heart
disease and RAS
J Nephrol 2009;22(1):13–16
RVH: ARAS Management (Contd)
 CORAL

The Cardiovascular Outcomes with Renal
Atherosclerotic Lesions (CORAL) study is
a National Institutes of Health–funded
multicenter trial testing the hypothesis that
 Stenting
atherosclerotic RAS in patients with
systolic hypertension reduces the incidence
of cardiovascular and renal events
 The CORAL study has completed enrollment
with over 900 patients, but results will not be
available for some time
Available at http://www.clinicaltrials.gov/ct/show/NCT00081731
RVH: ARAS Management (Contd)
 At this time, there is no clear benefit of revascularization
for ARAS,


Especially in patients for whom BP can be controlled
easily and who have no evidence of ischemic
nephropathy
The risks of the procedure may outweigh any potential
benefits
 Angioplasty with or without stenting may be of benefit in

Patients with HT that is difficult to control in the setting of
decreased renal perfusion, because uncontrolled
hypertension is a major cardiovascular risk factor
 Accordingly, aggressive treatment of hypertension
with medications is recommended
RVH: ARAS Management (Contd)
 Antihypertensive treatment may also include



ACE inhibitors and ARBs provided that
 Renal function is stable and that close follow-up is
available
Medical therapy should also include
 Statins to prevent further progression of
atherosclerotic plaques in the renal arteries and
 Cardiac prophylaxis with lowdose aspirin
Smoking should be strongly discouraged
TA: Indian Scenario
 Indian male patients with TA have a
higher frequency of hypertension and
abdominal aorta involvement while

Female patients have a tendency towards
involvement of aortic arch and its branches
Eur J Vasc Endovasc Surg 2007;33, 578-82
TA: Indian Scenario (Contd)
 The average age of the Indian patient
presentation is in the third decade

The disease has been observed to present
in
 Second
decade in Latin America,
 Third decade in Japanese and
 Fifth decade in Swedish patients
Eur J Vasc Endovasc Surg 2007;33, 578-82
TA: Indian Scenario (Contd)
 The majority of Indian patients had HT at
the time of presentation and only 16% of
patients had constitutional symptoms of
fever weight loss and arthralgia

HT has been a predominant feature in
most of the studies from India
 It
commonly results from the involvement of
renal arteries (involved in 20-90% cases in
different series)
Eur J Vasc Endovasc Surg 2007;33, 578-82
TA: Indian Scenario (Contd)
 As most of Indian patients present in the
chronic phase, steroid therapy has not
been used very commonly,

Though it is being employed more
frequently than in the past
Eur J Vasc Endovasc Surg 2007;33, 578-82
TA: Indian Scenario (Contd)
 Indian study

Surgical intervention consisting of bypass
procedures, autotransplantation or
nephrectomy was performed in 17 (13.6
%) and angioplasty in nine (7.2 %) patients
 Cure
and improvement in BP was observed
in 82.4 % and 77.8 % respectively

Adequate control of BP was achieved with
drugs only in 22 (22.2 %) patients
Q J Med. 1992;85:833-43.
TA: Indian Scenario (Contd)
 The clinical benefit of renal angioplasty
was seen in 85%of TA cases

However, re-stenosis occurred in 24.23%
cases at a median follow up of 4.6 years
 In earlier studies of balloon angioplasty
for TA,


Tyagi et al. reported a re-stenosis rate of
25.8% in 31 renal units, whereas
Sharma et al. reported re-stenosis rate of
20% in 40 patients
Eur J Vasc Endovasc Surg 2007;33, 578-82
TA: Indian Scenario (Contd)
 Although re-stenosis is a common
problem of PTRA for TA, repeat
procedures have provided good results
 In most angioplasty series of TA, tight
ostial stenosis and longer renal artery
stenosis length are associated with
higher re-stenosis rates
Eur J Vasc Endovasc Surg 2007;33, 578-82
Conclusions
 RVH is potentially remediable cause of
HT
 TA remains the commonest cause of
RVH in India

Better understanding of disease aetiology
and pathogenesis is required for better
outcomes in the future
Conclusions (Contd)
 ARAS and FMD are common causes of
RAS in western world
 Appropriate treatment continues to
evolve, but control of hypertension is
imperative
 Role of angioplasty is well accepted in
FMD but is not so clear in ARAS