Recent advances in renal hypertension

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Recent advances in renal hypertension
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Scope

• Renal hypertension
• Introduction
• Causes
• ARAS, FMD
• Pathophysiology
• Clinical features
• Diagnosis
• Imaging
• Management
• Conclusions

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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 20095(2)5659, Proc (Bayl Univ
Med Cent) 201023(3)24649
4
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 20095(2)5659, Proc (Bayl Univ
Med Cent) 201023(3)24649
5
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.
6
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.
7
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.
8
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.
9
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 20095(2)5659, Proc (Bayl Univ
Med Cent) 201023(3)24649
10
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

US Nephrology 20095(2)5659, Proc (Bayl Univ
Med Cent) 201023(3)24649
HT- Hypertension
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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 20095(2)5659, Proc (Bayl Univ
Med Cent) 201023(3)24649
12
RVH Pathophysiology
Safian Textor. NEJM 3446
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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 20095(2)5659, Proc (Bayl Univ
Med Cent) 201023(3)24649
14
RVH Pathophysiology (Contd)
US Nephrology 20095(2)5659, Proc (Bayl Univ
Med Cent) 201023(3)24649
15
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 20095(2)5659, Proc (Bayl Univ
Med Cent) 201023(3)24649
16
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 20095(2)5659, Proc (Bayl Univ
Med Cent) 201023(3)24649
17
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 20057(6)40511.
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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 20057(6)405411.
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RVH Diagnosis (Contd)

• Clinical findings associated with RVH

N Engl J Med 2001344(6)43142. Curr Cardiol
Rep 20057(6)40511 Kidney Int
200670(9)15431547
20
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 2001344(6)43142. Curr Cardiol
Rep 20057(6)40511 Kidney Int
200670(9)15431547
21
RVH Diagnosis (Contd)

• Clinical findings associated with RVH (Contd)

AAA abdominal aortic aneurysm CAD, coronary
artery disease PADperipheral arterial disease
N Engl J Med 2001344(6)43142. Curr Cardiol
Rep 20057(6)40511 Kidney Int
200670(9)154347
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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

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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

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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

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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

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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

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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

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RVH Management

• Treatment options include
• Pharmacological therapy with various
  antihypertensive medications,
• Percutaneous angioplasty with or without stent
  placement, and
• Surgical revision of RAS

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RVH Management (Contd)

• Availability of potent antihypertensive drugs and
  the advances in endovascular techniques, as well
  as stents, have made surgical treatment rarely
  necessary

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RVH Management (Contd)
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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

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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

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Fibromuscular Dysplasia, before and after PTRA
Atherosclerotic RAS before and after stent
Safian Textor. NEJM 3446
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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

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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 2009361(20)19531962
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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 2009361(20)19531962
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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

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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 2009150(12)840848
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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 200922(1)1316
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RVH ARAS Management (Contd)

• CORAL
• The Cardiovascular Outcomes with Renal
  Atherosclerotic Lesions (CORAL) study is a
  National Institutes of Healthfunded 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
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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

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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

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Conclusions

• RVH is potentially remediable cause of HT
• ARAS and FMD are common causes of RAS
• 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

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Thank You!