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Transcript
Renal Vascular Disease & HTN
Mark D. Purcell DO
Nephrology/Internal Medicine
Carolina Nephrology, PA
203 Mills Avenue
Greenville, SC 29605
(864) 271-1844
[email protected]
Hypertension and the Kidney
The Kidney and Hypertension
Chicken or the Egg?
Overview – Secondary Hypertension
 HTN affects >50 million adults in US
 95% - Essential HTN
 5-10% - “ Secondary” HTN
 Potentially curable disease

Often overlooked / under screened – OSA and Hyperaldosteronism

Controversy over screening and treatment

Expensive, index of clinical suspicion and knowledge of limitations
of different tests
Suspect Secondary Hypertension
 General principles:

New onset HTN if <30 or >50 years of age

HTN refractory to medical Rx (>3-4 meds)

Specific clinical/lab features typical for diagnosis
 Hypokalemia, epigastric bruits, differential BP in
arms, episodic HTN/flushing/palpitations
 Features of OSA (Obstructive Sleep Apnoea)
 OTC, Steroids, Licorice etc
RESISTANT HYPERTENSION
 Definition

BP > 140/90 mm of Hg on at-least three anti–hypertensive medications
(one diuretic)
 Prevalence - 10%
 Clinical conditions:

Non-compliance
Sub-optimal doses
White coat effect
Exogenous substances (cocaine)

Secondary causes



Causes of Secondary HTN
 Common
 Intrinsic Renal Disease
 Retention of salt

 Uncommon
 Pheochromocytoma

Glucocorticoid excess/
Cushing’s disease

Coarctation of Aorta

Hyper/hypothyroidism
Renovascular Disease
 RAAS
 Renal a. stenosis

Mineralocorticoid excess
 Aldosteronism

OSA (Obst. Sleep apnea)
 Sympathetic overactivity
Hypertensive
Nephrosclerosis?
Moser M and Setaro J. NEJM 2006;355:385-392
Kidney Disease in Hypertension
A Historical Perspective
 Ludwig Traube (Berlin, 1856)
“High BP Necessary”



… arterial pressure was
elevated to overcome
mechanical resistance …
through thickened arteries.
… increased BP pressure was
necessary for excretory
efficiency.
… concepts which were
unchallenged …
 Page (Cleveland, 1934)
“High BP Not Required for
Kidney Function”



Developed kidney clearance
techniques that estimated
kidney blood flow in humans.
Reduced elevated BP without a
fall in urea clearance.
Radical sympathectomy in
essential & malignant HTN safely
lowered BP w/o loss of function.
Traube L. Ueber den zusammenhang von herz und nierenkrankeiten. Berlin: Hirschwald, 1856.
Page IH. Effect on kidney efficiency of lowering blood pressure in cases of essential hypertension and nephritis. J Clin Invest
1934;13:909.
ESRD: Incident Counts & Adjusted Rates
By Primary Diagnosis
72%
illi
illi
lla
lla
Incident ESRD patients. Rates adjusted for age, gender, & race.
ESRD Care Only — $17.3 million USD
United States Renal Data Survey, 2006
Adjusted Relative Risk for Developing
ESRD Associated with BP Level
BP level (mm Hg)
Adjusted
relative risk
95% CI
<120/80
Reference
—
120-129/80-84
1.62
1.27-2.07
130-139/85-89
1.98
1.55-2.52
140-159/90-99
2.59
2.07-3.25
160-179/100-109
3.86
3.00-4.96
180-209/110-119
3.88
2.82-5.34
>210/120
4.25
2.63-6.86
Pohl MD et al. J Am Soc Nephrol 2005. Available at: http://www.jasn.org.
Nephrosclerosis
 Definition
 Stiff vessels from hypertension
 Hyaline in vessels, loss of glomeruli and
tubules from microvascular ischemia
 Called benign to distinguish clinical
course from malignant
Nephrosclerosis – Target
Regions
Arcuate arteries
Intralobular arteries
Afferent arteriole
Hypertensive Nephrosclerosis
 Two processes
 Loss of lumen through medial hypertrophy
(growth) and intimal thickening
(encroachment)
 Deposition and accumulation of hyaline
material (protein in origin, eg, C3b) in vessel
wall, causing further narrowing of vessel.
 Glomeruli
 Shrunken (ischemic)
Benign Hypertesion
Clinical Features of
Nephrosclerosis
 Proteinuria, variable, <1 g/d
 Uric acid elevations more common
 UA bland
 If SCr is elevated, even minimally, the
kidneys are usually small

Calculate GFR
Nephrosclerosis
 Occurs with aging
 Modest
 Accounts for most
of aging-related
decline of GFR
 Ethnic predilection
 African Americans
 Relatively
younger
 Worse histology
 SCr correlates with
histology
Case presentation 1
 41 yr old white female with no significant PMH
 Evaluated for kidney donation to her father
 Spiral CT: Single renal arteries B/L: 7-8 mm in size
 Reno gram:- Normal and 5/2011 – kidney donation
 14 months later she presented with HTN (BP -150/100 mm
of Hg) and mild renal insufficiency (creat.1.5 mg %)
Date
04/07/2012
08/22/2011
08/07/2011
08/02/2011
07/25/2011
07/10/2011
07/03/2011
Time
BUN
CREAT mg/dL
1.1
1.1
1.1
1.4
1.3
1.4
Presented with HTN &
1.5
renal Failure
15:52
16:45
09:45
14:07
15:00
00:00
15:21
23
18
25
29
36
34
05/25/2010
05/24/2010
05/23/2010
00:05 9
00:10 11
00:10 11
1.0
1.2
1.2
04/09/2010
11:02 9
0.8
kidney Donation
Differential Diagnosis ?
Hypertension and Azotemia
 Renal parenchymal disease
 Ischemic renal disease
 Reno-vascular stenosis (single kidney)
 Aortic Coarctation
 Vasculitis (PAN)
 Athero-embolic disease
What is next ?
ANGIOGRAM OF FIBROMUSCULAR DYSPLASIA
 Unique features of this case
 Presentation: Ischemic renal disease (HTN & azotemia)

? Silent severe FMD vs. Rapid progression FMD
gradient of > 120 mm of Hg)
(systolic

Failure to detect by CTA

? Unilateral (Recipient had no definite features of severe FMD)
Fibromuscular dysplasia
 10-25% of all RAS
 Young female, age 15-40
 Medial disease 90%, often involves distal RA
 ~ 30% progressively worsen but total occlusion is rare
 Treatment – Percutaneous Transluminal Renal
Angioplasty (PTRA)



Successful in 82-100% of patients
Restenosis in 5-11%
“Cure” of HTN in ~60%
Fibromuscular dysplasia
Medial Fibroplasia : 70-85 %
Classic “String of beads”
Perimedial Fibroplasia:10-25%
Small (focal) string of beads
Intimal Fibroplasia: 10%
Localized smooth stenosis
With Post-stenotic dilatation
Case presentation 2
 A 72 yr old Caucasian female
 Recent onset of mild kidney injury and HTN
 Meds: Prinivil, Cardizem & third unknown agent
 BP 200/100 mm of Hg, SCr. 1.6 mg/dL
 PMH: Smoker 50 pk.yrs & Hypercholesterolemia
Date
08/28/2011
08/21/2011
08/17/2011
08/17/2011
08/17/2011
08/16/2011
07/25/2011
07/24/2011
06/12/2011
05/23/2011
05/03/2011
04/26/2009
02/23/2009
Time
00:00
00:00
21:00
14:30
05:30
19:38
15:10
19:48
17:10
16:01
11:10
21:45
11:33
BUN
96
62
41
39
39
31
37
34
42
34
14
19
CREAT mg/dL
5.8
3.5
2.3
2.2
2.2
1.9
1.7
PTRA with Stent
1.6
Referral to Nephrology
2.0
1.9
1.5
1.2
0.9
Case presentation 2
 Post-PTRA outcome

Severe renal failure

Severe HTN and CVA

Patient died a week later
Case presentation 3
 A 72 yr old AA male, Smoker with h/o DM, HTN, CAD,
Hypercholesterolemia & CRF
 Hytrin 5 mg QD, Lasix 80 mg BID, Vasotec 20 mg BID, Norvasc 5
mg BID, Clonidine 0.2 mg TID, Metoprolol 100 mg BID and K-Dur
20 meq TID
 BP 150/100 mm of Hg
 Sr. Creat. 1.8 –2.3 mg/dL
MRA - BILATERAL RAS
Case presentation 3
 Bilateral renal artery stenosis
 PTRA with stent placement
 BP – 130 / 85 mm Hg on 3 anti – hypertensive
drugs
 2 yrs later his Sr. Creat. is 1.6 –1.7 mg/dL
RENOVASCULAR HYPERTENSION (RVH)
 Definition of Reno-vascular Hypertension
 Hypertension cured or improved by reversal of
stenosis
 Confirmation is retrospective
 Hypertension
Reno vascular stenosis
 Cause and Effect Relationship
CAUSES OF RVH
 Atherosclerotic RAS (90%)
 Usually ostial and associated with diseased aorta
 Fibromuscular dysplasia
 Aortorenal dissection
 Vasculitis involving the renal artery (i.e. PAN)
 AVMs involving the renal artery
 Irradiation of the renal artery
 Scleroderma
Characteristics of Atherosclerotic Renal-Artery Stenosis and Fibromuscular Dysplasia.
Dworkin LD, Cooper CJ. N Engl J Med 2009;361:1972-1978.
PREVALENCE OF RAS
 Hypertensive patients
 PCP clinic
 hospital based clinic
 specialized HTN clinic
 Autopsy series >60yrs
- 1%
- 5%
- 40%
25 - 30%
 Extrarenal vascular diseases 18 - 42%
ASSOCIATION BETWEEN DEGREE OF
STENOSIS AND HYPERTENSION
DEGREE OF
STENOSIS
HYPERTENSION
0 –49%
46%
50 –75%%
Unilateral
Bilateral
78%
93%
>75%
Unilateral
Bilateral
86%
94%
Morphological stenosis may not always result in clinical HTN
DIAGNOSIS OF RAS
(Renal A. Stenosis)
 Commonest form of curable hypertension if diagnosed
early
 Less amenable to pharmacotherapy
 Worse prognosis than primary hypertension
 Definitive therapy mandates diagnosis of RAS
 4-8 % of all ESRD : Ischemic Nephropathy
RVH - CLINICAL DILEMMA
1.
Who should be investigated for RVH?
2.
Which is the ideal screening test ?
3.
What is the functional relevance of morphological stenosis ?
4.
How to recognize critical RAS in timely manner ?
5.
How to predict response to Renal Revascularization?
RAS – Hemodynamic significance
 Definition for Hemodynamically significant RAS

Stenosis > 75%

> 50% stenosis with poststenotic dilitation

Luminal stenosis between 50 –75%



Peak SBP gradient of >10 % across the stenosis
Mean pressure gradient > 5 % or 10 mm of Hg
Resistive Index of < 80 (PSV – EDV / PSV*100)
RAS – Clinical significance
 Morphological RAS
Clinically significant
 BP uncontrolled on medical management
 Impairment of renal function
 Evidence of nephron loss on follow-up imaging studies
 Poor Quality of life – pulmonary edema or resistant HTN
 Decision to re-vascularize depends up on
clinical significance rather than morphological
or hemodynamic significance
Who should be investigated for RVH?
Prediction Rule for Quantifying the Probability of
Renal Artery Stenosis
Predicted probability of renal artery stenosis in patients with
drug-resistant hypertension as a function of the sum score.
SUGGESTED WORK-UP FOR RVH
INDEX OF CLINICAL SUSPICION
LOW (1%)
NO FURTHER WORK UP
-
MODERATE
(5-15%)
CAPTOPRIL RENOGRAM
CAPTOPRIL TEST
RV RENINS
MRA OR DUPLEX SCAN
HIGH (>25%)
ARTERIOGRAM
+
Which is the ideal screening test ?
Diagnostic Imaging Tests for Renal-Artery Stenosis.
Dworkin LD, Cooper CJ. N Engl J Med 2009;361:1972-1978.
So some tests are inconclusive while others
are expensive or have inherent risks, does it
really matter to pursue RAS in today’s
health care system???
Dismal Prognosis Associated with
RAS
 3 year mortality


26% in patients treated with stents (Circulation 1998;98:642-647)
28% in patients managed medically (Mayo Clin Proc 2000;75:437)
 4 year mortality



43% in patients with RAS discovered incidentally at cardiac
catheterization (Kidney International 2001;60:1490-1497)
35% in patients with RAS discovered incidentally at cardiac
catheterization (JASN 1998;9:252-256)
26% in a multi-center study of patients undergoing percutaneous renal
revascularization (Circulation 1998;98:642-647)
 5 year mortality

33% in a single-center study of patients undergoing percutaneous renal
artery revascularization (Catheter Cardiovasc Interv. 2007;69:1037)
Effect of RAS on Prognosis –
Relative Five year Survival
100
Survival
80
60
40
20
0
Breast
Cancer
RAS
Colorectal
Cancer
Non-Hodgkins
Lymphoma
Ries LAG et al. SEER Cancer Statistics Review, 1973-1998.
National Cancer Institute. September 2000.
Clinical Events in Patients With RAS
Claims data from a 5% random sample of the United States Medicare
population were used to select patients without atherosclerotic renovascular
disease in the 2 years preceding December 31, 1999 (N= 1,085,250), followed
J Am Coll Cardiol Intv 2009;2:175-182
until December 31, 2001.
INDICATIONS FOR ANGIOPLASTY
IN HEMODYNAMICALLY SIGNIFICANT RAS
 HYPERTENSION CONTROL
 Reasonable likelihood of cure
 Refractory, accelerated or malignant HTN
 FMD suspected clinically
 Intolerant or non-compliant to medications
 Onset of HTN < 30 or > 60
 RENAL SALVAGE
 Loss of renal mass or function unexplained or on medication (ACE-I or ARB)
 Progression of RAS under surveillance
 CARDIAC DISTURBANCE SYNDROME
 Unstable angina or flash pulmonary edema
INDICATIONS FOR RENAL ARTERY
STENT DEPLOYMENT
 Failure to attain satisfactory angioplasty results
 > 30 % stenosis
 Persistent hemodynamically significant gradient
 Flow limiting Dissection
 Ostial stenosis – standard of care
 Ostial stenosis that has normal diameter of 5 mm or more
(restenosis rate is higher)
 Re-stenosis of successful previous angioplasty
CONTRAINDICATIONS FOR RENAL
ARTERY STENT DEPLOYMENT
 Inelastic stenosis that cannot be reduced to < 50 %
by angioplasty
 Presence of sepsis
 Stent would preclude surgical salvage should
re-stenosis occur
 Stenosis of artery with 4 mm or less in diameter
COMPLICATIONS OF RENAL
REVASCULARIZATION
Controversies in ASO –RAS management
 Optimal non – invasive test
 ACEI / ARB in Bilateral RAS
 Follow up protocol for Imaging in patients on
medical management
 Medical vs. Interventional management
Angioplasty and STent for
Renal Artery Lesions (ASTRAL)
NEJM 2009;361:1953-1962
ASTRAL Trial
Substantial atherosclerotic RAS
Suitable for endovascular revascularization
Patient's doctor was uncertain that the patient would benefit from
revascularization
Revascularization
(n = 403)
No revascularization
(n = 403)
with angioplasty and/or stent
(and medical treatment)
Medical treatment according to local
protocol
PATIENT CHARACTERISTICS
Revasc.
Medical
P-value
70 (42 – 86)
71 (43 – 88)
0.7
Male
63%
63%
0.9
Current smoker
20%
22%
0.5
Diabetes
31%
29%
0.5
CHD
49%
48%
0.2
PVD
41%
40%
0.7
40.3
(5.4 – 124.5)
39.8
(7.1 – 121.7)
0.7
Mean age (range)
GFR (ml/min)
Procedural Complications
 38 peri-procedural complications in 31 of 359 patients
(9%) who underwent revascularization
 19 of these events were considered to be serious
complications




Pulmonary edema (1) and Myocardial infarction (1)
Renal embolizations (5), Renal arterial occlusions (4) and
Renal-artery perforations (4)
Femoral-artery aneurysm (1)
Cholesterol embolism leading to peripheral gangrene and
amputation of toes or limbs (3)
Blood Pressure
The ASTRAL Investigators. N Engl J Med 2009;361:1953-1962.
Kaplan–Meier Curves for the Time to the First Renal and Cardiovascular Events.
The ASTRAL Investigators. N Engl J Med 2009;361:19531962.
Kaplan–Meier Curves for Overall Survival.
The ASTRAL Investigators. N Engl J Med 2009;361:1953-1962.
• “An important limitation of our trial concerns the population that
we studied. As noted, patients were enrolled in the trial only if
their own physician was uncertain as to whether revascularization
would provide a worthwhile clinical benefit.”
• Patient selection (single center)
–
–
–
–
508 patients with atherosclerotic renovascular disease
Of these, 283 patients had renal-artery stenosis of more than 60%
71 underwent randomization
24 underwent revascularization outside the trial
•
•
–
poorly controlled hypertension
rapidly declining renal function,
188 received medical treatment only.
Criticisms of ASTRAL
 Selection bias/ Inexperienced Operators
 Reduction in number of anti-HTN Rx in stent-treated





patients
Patients with severe RAS were not enrolled
Not all patients in the intervention group had stenting
High Adverse Event Rate
Trial Centers were not high-volume centers
Await Coral (Cardiovascular Outcomes in Renal
Atherosclerotic Lesions)
Where do we stand now?
 In the absence of trials showing benefit from
revascularization over conventional therapy and the
significant risk of complications it seems reasonable to
restrict procedures to patients who fail medical therapy
with:





resistant or poorly-controlled hypertension (pts on many meds)
recurrent flash pulmonary edema
dialysis-dependent kidney failure resulting from renal artery
stenosis
chronic renal insufficiency and bilateral renal artery stenosis
renal artery stenosis to a solitary functioning kidney.
Agency for Healthcare Research and Quality
(AHRQ)
Available at www.guideline.gov
Summary
 RAS is an unusual cause of hypertension but a
common finding in patients with vascular disease
 RAS identifies patients with very poor prognosis and a
high risk of cardiovascular events
 Revascularization will benefit select patients with RAS
but predicting who responds favorably is challenging
 A better understanding of the pathophysiology of RAS
is needed in order to design more effective therapies