evaluation and treatment of renal hypertension dr

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


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)


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.


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.


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


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


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


ARAS (Contd)

Aortogram demonstrating high-grade stenosis affecting the left renal artery

Quantitative measurements indicated more than 86% lumen obstruction


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


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


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



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



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


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.


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


Clinical findings associated with RVH (Contd)

ACE: angiotensin-converting enzyme; ARBs: angiotensin II receptor blockers; RAS: renal artery stenosis



Clinical findings associated with RVH (Contd)

AAA: abdominal aortic aneurysm; CAD, coronary artery disease; PAD:peripheral arterial disease


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


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


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


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


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


TA: Diagnostic criteria


Modified diagnosis criteria for TA: Sharma et al

TA: Diagnostic criteria (Contd)


Modified diagnosis criteria for TA: Sharma et al(Contd)

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

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


TA: Clinical features (Contd)


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


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%



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



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


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


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


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


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


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


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


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


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


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



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)



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



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.


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



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


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

evaluation and treatment of renal hypertension dr

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