Hypertension and the Kidney The Kidney and Hypertension
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Transcript Hypertension and the Kidney The Kidney and Hypertension
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