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Recent advances in renal hypertension

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Title: Recent advances in renal hypertension


1
Recent advances in renal hypertension
2
Scope
  • Renal hypertension
  • Introduction
  • Causes
  • ARAS, FMD
  • Pathophysiology
  • Clinical features
  • Diagnosis
  • Imaging
  • Management
  • Conclusions

3
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
11
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
13
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.
18
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.
19
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
22
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

23
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

24
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

25
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

26
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

27
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

28
RVH Management
  • Treatment options include
  • Pharmacological therapy with various
    antihypertensive medications,
  • Percutaneous angioplasty with or without stent
    placement, and
  • Surgical revision of RAS

29
RVH Management (Contd)
  • Availability of potent antihypertensive drugs and
    the advances in endovascular techniques, as well
    as stents, have made surgical treatment rarely
    necessary

30
RVH Management (Contd)
31
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

32
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

33
Fibromuscular Dysplasia, before and after PTRA
Atherosclerotic RAS before and after stent
Safian Textor. NEJM 3446
34
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

35
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
36
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
37
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

38
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
39
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
40
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
41
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

42
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

43
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

44
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