Hypertension in

Hemodialysis Patient

Ri 呂世和

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 Outline
 Pathophysioloy
 Dry weight
 “Lag phenomenon”

 Management

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 Background
 HEMO study: HTN in > 70% HD p’ts
 HTN during HD  CAD, CHF, death
 High SBP: a major predictor of mortality in
HD p’ts

Am J Nephrol 2001; 21:280-8

JAMA 2002; 287:1548-55
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Pathophysiology

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 Pathophysiology
 Classic mechanism for HTN in ESRD has
always been thought to be ECV expansion
 Blumberg: BP could be controlled in HD
p’ts by Na restriction alone
 Vertes: BP could be controlled in majority
of dialysis p’ts through “dry-weight method”
 Absence of edema not synonymous with
reaching dry weight
Lancet 1967; 2:69-73
N Engl J Med 1969; 280:978-81
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 Pathophysiology
 “Volume-dependent” HTN
 Remain normotensive w/o anti-HTN
medications as long as dry weight maintained

 “Volume-independent” HTN
 Minority continue to have HTN despite
maintaining dry weight
 Numerous medications
 Bilateral nephrectomy

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Mechanism of
HTN in
HD patients

Am J Kidney Dis 2004; 43:739-51

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 Pathophysiology
 The pathophysiology of HTN in HD p’ts is
multifactorial
 Majority:
 Volume dependent
 Na balance

 Dry weight

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 Dry Weight
 A consensus definition of “dry weight” notoriously
complicated

 Absence of overt PE findings of volume overload

( JVE, rales, edema…)
 The lowest weight p’t can tolerate before
hypotension or symptoms
 From Tassin:
The postdialysis weight at which the p’t remains
normotensive when off all anti-HTN medications
and despite interdialytic weight gain
Nephron Physiol 2003; 93:94-10110
 Dry Weight
 Accurate clinical estimation of the “true dry
weight” can be difficult
 ↑vena cava diameter despite no PE findings

 Overestimation will contribute to HTN

 Only 2% BW difference between
normotensive and HTN

Am J Kidney Dis 1998; 32:720-24

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 Dry Weight
Dry weight will constantly change based
on nutritional status
 Subtle loss of true dry weight !

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 Volume-dependent HTN
 Tight control of ECV prevents HTN in HD
p’ts

 Long, slow HD (18 hrs per week)

 Minor interdialytic weight gain
 lower frequency of HTN
 less anti-HTN drugs
 higher 10-yr survival rate opposed to
conventional HD (12 hrs per week)
Nephrol Dial Transplant 1999; 14:919-22
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 Volume-dependent HTN
 ECV↓not translate into immediate BP↓
 Fluid loading will not necessarily acutely raise
the BP

 “Lag phenomenon”: adequate BP control often

does not immediately occur after ultrafiltration to
“dry weight”, especially in chronic volume
overloaded p’ts

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 Lag Phenomenon
 Once dry weight is achieved, BP often does
normalize but may take weeks to months
 MAP 111.3 mmHg  94.4 mmHg after reduction
to dry weight over the first 6 months
 P’ts weight↑without BP↑, a reflection of improved
nutrition, not of ECV
 Only a sustained normalization of ECV will result
in perfect BP control

Nephrol Dial Transplant 1999; 14:121-4

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 Lag phenomenon
ECV↑ CO ↑ CO normal, PVR↑
 BP↑ pressure natriuresis (kidney)
 BP normal

 What links ECV↑and PVR↑?

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 Endogenous “toxins”
 Mouse experiments:
endogenous circulating “toxins” contribute to
HTN

 Na, K-ATPase inhibitor

 Ouabain
 Ouabain-like compound (OLC)
 Digoxin-like immunoreactive substance (DLIS)
 Inhibitor of NO production
 Asymmetrical dimethyl-L-arginine (ADMA)
Eur J Biochem 2002; 269:2440-8 17
 Na, K-ATPase inhibitors
Persistent volume expansion
 DLIS and OLC↑ vasoconstriction
Blocking these substances with antibodies
 lower BP in rat models associated with
ECV expansion
 Circulating Na, K-ATPase inhibitors
 identified in HD p’ts
 correlated with ECV expansion
Circulation 2002; 105:1122-7 18
 Na, K-ATPase inhibitors
 Removal of these substances with HD is
insignificant
 Very large Vd
 Long elimination half-life (36~48 hrs)

Continued circulation of DLIS and OLC

 lag phenomenon

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Na, K-ATPase inhibitors

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Am J Kidney Dis 2004; 43:739-51
 Inhibition of NO
 Nitric Oxide (NO)
 important vasodilator made by endothelial cell

 critical role in maintaining vascular tone

 Blockade of NO production

 vasoconstriction and HTN in animals

 Recently, an endogenous inhibitor of NO
production has been discovered and shown to
be elevated in subjects with CKD or ESRD

Lancet 1992; 339:572-5 21

 Inhibition of NO
 Asymmetrical dimethyl-L-arginine (ADMA)

Salt loading
 plasma NO production↓ , ADMA↑
Plasma ADMA ↓ with HD
 mean 24-hr ambulatory BP↓
 ADMA metabolism↓in oxidative stress (DM,
hyper-CHO…)

Circulation 2000; 101:856-61

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Inhibition of NO

Am J Kidney Dis 2004; 43:739-51

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Management

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 Goal

 Reach a level of ECV:

 Not require anti-HTN medications
 Free of orthostatic hypotension

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 Initial Phase
 Clinical assessment of volume status
 Jugular vein
 Peripheral edema

 CXR …

 Dietary salt restriction < 5~6 g /day

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 Ultrafiltration Phase
 Ultrafiltration initiated, “probing” for true
dry weight
 Early ultrafiltration phase: tapering of anti-
HTN medications
 Anti-HTN medications
 not allow vascular system to properly adapt to
ongoing ultrafiltration
 result in repeated hypotension

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 Lag Phase
 Patience: p’t may remain hypertensive for
weeks during this period
 Anti-HTN medications should not be
reinstituted
 A point will be reached at which the p’t can
become normotensive w/o medications

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 Longer Sessions
 Long, slow HD (18 hrs per week)
 Minor interdialytic weight gain
 lower frequency of HTN
 less anti-HTN drugs
 higher 10-yr survival rate opposed to
conventional HD (12 hrs per week)

Nephrol Dial Transplant 1999; 14:919-22

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 Longer Sessions
 Converting to nocturnal HD
 SBP: 145  122 mmHg
 a decline in the number of anti-HTN
medications used
 regression of LVH

 Decreased variability in ECV

 “Daily HD”

Kidney Int 2002; 61:2235-9 31

Effect of Prolonged HD

Semin Dial 2004; 17:295-8

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 HD Dose and High-flux HD

 Whether↑dose of HD or using high-

flux membrane dialyzers enhance
removal of these vasoactive
substances and therefore improve BP
control ?

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 Impact of HD Dose

 HEMO study: NO mortality benefit

 BP control could be achieved
independently of Kt / V
 Shorter HD sessions (8  5 hrs) with
unchanged Kt / V  MAP↑

N Engl J Med 2002; 347:2010-9

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 High-flux HD

High-flux or high-efficiency HD
 No improvement in BP control or
anti-HTN medications

Am J Kidney Dis 1998; 31:618-23

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 Acute HTN Episode

 Once during lag phase

 BP↑ to SBP >180 or DBP>110
 symptomatic HTN

 Lisinopril for HTN in HD has been

shown to↓BP w/o causing hypotensive
episodes during HD
 Atenolol also effective
Am J Kidney Dis 2001; 38:1245-50
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 Acute HTN Episode
 These medications, esp. ACEI:
 well tolerated
 prevent serious complications of acute HTN

 work synergistically with HD

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 Common Scenarios
 Thirst, acute falls in BP  could not tolerate HD
 LVH, diastolic dysfunction  sensitive to volume
reduction and susceptible to dialysis
hypotension
 Strict volume control  long-term regression of LVH
 DM  autonomic dysfunction
 Shorter HD time

 more drastic volume changes

 volume removal more difficult
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 Common Scenarios
 Prematurely claim
 at true dry weight
 classify HTN of volume-independent

 Blood volume usually re-equilibrates with

fluid from interstitial space a few hours
after HD

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 Common Scenarios
 These symptoms transient and might
improve in later HD  should not exclude
further ultrafilitration
 Failure to withdraw anti-HTN medications
also contribute to refractory hypotension

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 Common Scenarios
 When dialysis hypotension prevent further
ultrafiltration
 prolonged time
 extra HD sessions

 ↓UFR

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 Important Concepts
 The focus of treatment centers around
 strict volume control
 salt restriction
 adequate BP control can usually be achieved
with conventional HD (4 hrs, 3 times weekly)

 The “lag period” in conventional HD

 not necessarily prolonged
 variable between p’ts, from days to months

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 Important Concepts

Dry weight fluctuate depending on

nutrition status and muscle mass
 not static, must be frequently
reassessed

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 Evaluation of Volume
 Noninvasive evaluation of volume status
 Ultrasound measurement of IVC diameter
 Multifrequency bioimpedance

 May be helpful in difficult cases

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 Reinstitution of Medication
A minority remain hypertensive despite
aggressive UF
 volume-independent HTN
 require reinstitution of anti-HTN
medications

 Choice of medication: concomitant

disease
 CAD  beta-blocker
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 Reinstitution of Medication

 ACEI preferable
 fewer hypertensive episodes
 regression of LVH

 favorable survival

 synergy with UF

Am J Kidney Dis 2002; 40:1023-9

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 Reinstitution of Medication

 Avoid
 minoxidil: fluid retention
 medications altering normal
neurohormonal/sympathetic response to UF

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 Reinstitution of Medication
 Excessive volume expansion lead to
resistance to newly started medications
 Starting anti-HTN medication should not
preclude from trying to reach or maintain
dry weight

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Am J Kidney Dis
2004; 43:739-51
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 Conclusions
 Longer HD sessions
 using the dry-weight method

 can control HTN w/o addition of

medication

 Time to correction of BP relate to

 severity and duration of previous volume
expansion
 degree of elevation of these factors

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 Conclusions
 HTN of volume expansion
 long lasting
 critically important in maintaining a normal
ECV

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 Take Home Message

 Therapeutic plan
 脫乾

 Lag
phenomenon
( 怎麼來的，怎麼回去 )

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Am J Kidney Dis
2004; 43:739-51
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Thanks for Your Attention !

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