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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 high-grade 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- HypertensionUS 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 (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 contrast-
induced 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
Eur J Vasc Endovasc Surg 2007;33, 578-82
Modified diagnosis criteria for TA: Sharma et al
TA: Diagnostic criteria (Contd)
Eur J Vasc Endovasc Surg 2007;33, 578-82
Modified diagnosis criteria for TA: Sharma et al(Contd)
TA: Diagnostic criteria (Contd)
Eur J Vasc Endovasc Surg 2007;33, 578-82
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
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
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: 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
CT angiogram obtained in a 45 y.o. woman presenting with new onset RVHAneurysmal 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
RVH: FMD Case
Fibromuscular Dysplasia, beforeand after PTRA
Atherosclerotic RAS before and after stentSafian & Textor. NEJM 344:6;
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 lipid-
lowering 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