Hyertension in patients on regular hemodialysis

HYPERTENSION IN PATIENTS

ON REGULAR HEMODIALYSIS

Prepared by

Dr/ Ehab Ashoor M.B.B.Ch. Alex. University

M.Sc. Internal Medicine, Cairo University

TALK OUTLINE

General view

Pathogenesis

Blood pressure measurement in dialysis patients

Management of high blood pressure in hemodialysis patients:

Target blood pressure of hypertensive dialysis patients

Algorithm for blood pressure control in dialysis patients

Intradialytic hypertension

Hemodialysis patients admitted with hypertensive urgency

General view Hypertension is common in dialysed patients

- at pre-dialysis state >80%,

- in patients with haemodialysis >60%,

- in those with peritoneal dialysis >30 %

The leading cause of death in dialysed patients

is cardiovascular!

Rahman M, Smith MC. Hypertension in hemodialysis patients. Current Hypertension Reports 2001; 3: 496-502.

General view But:

in dialysed patients the relationship between

hypertension and cardiovascular mortality/morbidity

is controversial because of

- the high prevalence of co-morbid conditions,

- by the underlying vascular pathology and

- by the effects of

- dialysis on blood pressure

- age

- left ventricular hypertrophy/dysfunction (also

more prevalent in patients with hypertension)

- poor nutrition .

General view In patients on hemodialysis, hypertension has been

associated with:

- stroke,

- MI,

- CHF,

- ventricular arrhythmias and

- progression of atherosclerosis

General view Characteristics of cardiovascular

complications in patients on dialysis

Hypertension present in 60-90%

LVH: 90%

Total mortality: 12-25% - CV mortality: 60-70%

CHD: 17x mortality

Risk factors 1 mm Hg icrease in MAP = 35% increase in CV morbidity

5 mm Hg increase in MAP = 3% increase in the risk of LVH

PATHOGENESIS

Putative Pathogenetic Mechanisms of Hypertension in ESRD Patients

Expanded extracellular fluid volume

Renin angiotension aldosterone stimulation

Increased sympathetic activity

Endogenous digitalis-like factors

Prostaglandins/bradykinins

Altered function of endothelium-derived factors

Erythropoietin administration

Nephron number

Parathyroid hormone secretion

Calcified arterial tree

Worsening of pre-existing essential hypertension

Renal vascular disease

EXPANDED EXTRACELLULAR FLUID VOLUME

Volume expansion is perhaps the most important factor in the development and maintenance of hypertension in dialyzed patients

It leads to an elevation in BP through the combination of an increased in cardiac output and an inappropriately high systemic resistance

INCREASED SYMPATHETIC ACTIVITY

Sympathetic overactivity is a common finding in ESRD

The afferent signal may arise within the kidney because sympathetic activation is not seen in aphrenic patients

Chemoreceptors within the kidney by uremic metabolites may be important in generation of these signals

ENDOGENOUS DIGITALIS-LIKE SUBSTANCE

It is believed to be produced in either the hypothalamus or adrenal cortex

Because it inhibits Na+-K+ ATPase activity, cytosolic sodium increases, inhibiting calcium outflux, and causing increased smooth muscle calcium content leading to increased smooth muscle tone

ENDOTHELIUM-DERIVED FACTORS

The abnormal endothelial release of hemodynamically active compounds

Elevated plasma levels of endothelin-1, the potent vasoconstrictor, had been found in uremic patients

Uremic plasma contains a higher level of an endogenous compound, asymmetrical dimethylarginine, that is an inhibitor of NO synthesis

ERYTHROPOIETIN

An increase in BP of 10mmHg or more occurs in approximately one third of the patients with renal failure who are treated with erythropoietin

Through increased total peripheral resistance related to increased viscosity and decreased hypoxic vasodilatation

HYPERPARATHYROIDISM

Increase in intracellular calcium induced by parathyroid hormone excess cause vasoconstriction and hypertension

Either vitamin D administration or parathyroidectomy has been shown to lower blood pressure

Blood pressure measurement

in dialysis patients

Pre- or post-dialysis blood pressure measurements

in patients with hemodialysis may be misleading for

the diagnosis of hypertension:

- the pre-dialysis systolic blood pressure may

overestimate by an average of 10 mmHg

- the post-dialysis systolic blood pressure may

underestimate by an average of 7 mmHg

Blood pressure readings over a period of 1 to 2 weeks rather than

isolated readings should be used

Luik AJ, Kooman JP, Leunissen ML. Hypertension in hemodialysis patients: Is it only hypervolaemia?

Nephrol Dial Transplant 1997; 12: 1557-60.

Blood pressure measurement


Ambulatory blood pressure monitoring (ABPM)

appears to be reproducible in pts. on hemodialysis.

Blood pressure is frequently

- high in pre-dialysis state,

- it falls immediately after dialysis, and then

- it gradually increases during the inter-dialytic period.

ABPM may be useful in determining “systolic blood pressure

load”(the amount of time that the patient′s systolic Bp exceeds normal values) which

is an important factor in the development of left ventricular hypertrophy.

- Pre-dialysis blood pressure correlates better with

LVH than post-dialysis blood pressure.

- The dialyzed patients usually lose the diurnal variation

in blood pressure and consequently these patients develop

nocturnal hypertension.

- Home blood pressure measurement, an increasingly popular

method, may be useful to estimate the blood pressure control

also in dialysed patients

Conion PJ, Walshe JJ, Heinle SK et al. Predialysis systolic blood pressure correlates strongly with mean 24-hour systolic blood pressure

and left ventricular mass in stable hemodialysis patients. J Am Soc Nephrol 1996; 7: 2658-63.

Agarwal R. Role of home blood pressure monitoring in hemodialysis patients. Am J Kidney Dis 1999; 33: 682-7.

Management of high blood pressure in

hemodialysis patients

Improved survival due to adequate blood pressure

control of dialysed patients has been clearly demonstrated,

stressing the importance of adequate antihypertensive treatment.

Salem MM, Bower J. Hypertension int he hemodialysis population: any relation to one-year survival? Am J Kidney Dis 1996; 28: 737-40.

Target blood pressure of hypertensive

dialysed patients

The pre-dialysis & post-dialysis Bp goals should be <140/90

mmHg & <130/80 mmHg respectively (C). In some younger

patients the target Bp may even be set as low as 120/80

mmHg. In patients with reduced vascular & cardiac

compliance, Bp goals need to be higher.

The reasonable target goal of a mean ABPM value

- during the day < 135/85 mmHg

- by night < 120/80 mmHg.

CAUTION! Very low systolic blood pressure (<110 mm Hg)

may be associated with enhanced cardiovascular mortality

Henrich WL, Mailloux LU. Hypertension in dialysis patients. Rose B. UpToDate online 11.3, 2004, http://www.uptodate.com

http://www.uptodate.com/

Algorithm for blood pressure control


1. Estimate dry weight

2. Initiate non-pharmacological treatment

3. Attain dry weight

4. Start or increase the dose of antihypertensives

to maintain BP below 140/90 mmHg

Fishbane S, Maseka JK, Goreja MA et al. Hypertension in Dialysis Patients . In Cardiovascular Disease in End-stage Renal Failure.

Loscalzo J, London GM. Oxford University Press, New York, USA, 2000. pp 471-484.

Clinical definitions of stable “dry weight”

- either the blood pressure has normalized or

- symptoms of hypervolemia disappear (not merely the absence

of edema);

- after dialysis seated blood pressure is optimal, and

- symptomatic orthostatic hypotension and clinical signs of

fluid overload are not present;

- at the end of dialysis patients remain normotensive until the

next dialysis without antihypertensive medication.

- No HTN (pre-dialysis Bp at the beginning of the week < 140/90 mmHg)

- No peripheral edema

- CXR; no pulmonary congestion & cardiothoracic ratio ≤ 50% (≤ 53% in females)

- Absence of edema does not exclude the hypervolemia

DRY WEIGHT

Not merely the absence of edema, but the body sodium content and volume of body water below which further reduction results in hypotension

Volume removal to correct clinical fluid overload and optimized seated BP without symptomatic orthostatic hypotension after dialysis

Body weight at the end of dialysis at which the patient can remain normotensive until the next dialysis without antihypertensive medication

Salt & water balance: Patient compliance is often suboptimal & so, heavy reliance is placed on dialysis UF capacity to remove this excess fluid

LAG PHENOMENON

In new patients starting dialysis, some period of time passes before volume is controlled, dry weight is achieved, and BP is controlled; this period has been called the lag phenomenon

This is the time required to convert the patient from a catabolic to an anabolic state while the extracellular fluid space slowly stabilized

Algorithm for blood pressure control


5. If BP is not controlled or dry weight not attained in 30 days,

consider:

- 24-48 hours ABPM

- increasing the duration of dialysis to facilitate removal

of fluid and attainment of dry weight

- increasing the dose or number of antihypertensives

6. If BP remains uncontrolled, consider:

- evaluating for secondary forms of hypertension

- peritoneal dialysis

- bilateral nephrectomy (exceptional)

Fishbane S, Maseka JK, Goreja MA et al. Hypertension in Dialysis Patients . In Cardiovascular Disease in End-stage Renal Failure.

Loscalzo J, London GM. Oxford University Press, New York, USA, 2000. pp 471-484.

COMMON CAUSES OF SECONDARY HYPERTENSION

Primary aldosternism

Pheochromocytoma

Cushing‘s syndrome

RAS & renal diseases

Obstructive sleep apnea

Obesity (metabolic syndrome)

Non-pharmacological treatment of

hypertension in dialysed patients

Important remarks:

-Control of plasma volume can either normalize or help to

normalize blood pressure in dialysed patients.

- Fluid removal predisposes to episodes of hypotension during

hemodialysis treatment.

-Hypotension is one of the important cardiovascular

risk factors.



- Aerobic exercise

- Control of salt and fluid intake

- Cessation of smoking

- Weight reduction

- Avoidance of alcohol

- Long, slow and more frequent hemodialysis treatment

- Bilateral nephrectomy



- Aerobic exercise

- Control of salt and fluid intake - Cessation of smoking

- Weight reduction




To avoid large inter-dialytic weight gains, patients should

restrict salt intake (750 to 1000 mg of sodium/day). This also

decreases thirst and improves patient’s compliance.

A fixed or a programmed decrease in the concentration of

sodium in the dialysate (from 155 to 135 mEq/L) with

combination of dietary salt restriction, may result in smaller

doses of antihypertensive drugs to control blood pressure.



- Aerobic exercise



- Weight reduction


- Long, slow and more frequent hemodialysis

treatment - Bilateral nephrectomy

The long, slow hemodialysis treatment (eight hours, and

three times a week) is associated with the maintenance of

normotension without medications in almost all patients,

as this decreases afferent renal nerve activity and efferent

sympathetic activation.

Nocturnal hemodialysis treatment (six or seven nights a

week during sleep hours) can also normalize blood pressure

without medications in most of the patients.

More frequent hemodialysis treatment (two hours six times

per week) may also be associated with normotension without

medications and with regression of left ventricular hypertrophy.



- Aerobic exercise



- Weight reduction




Bilateral nephrectomy may be considered in:

- noncompliant individuals

- with life-threatening hypertension

- blood pressure cannot be controlled with any of the

above detailed dialysis modality.

Pharmacological treatment of hypertension

in dialyzed patients

Suggested use of antihypertensive drugs in hemodialysis patients

(which drug - when)

Drugs Compelling indication Specific side-effects Special precautions

ACE inhibitors LVH, CHF, DM, Anaphylactoid reactions with

AN69 dialyzer

DHP-CCB CHD

Non-DHP-CCB CHD No comb. with BBL

BBL CHD Excessive bradycardia No comb with

with liposoluble compounds non-DHP-CCB

Centrally act. none Post-dialysis rebound Avoid

agents with methyldopa

ABL Dyslipidemia Severe hypotension

Insulin resistance

Direct Hypertensive In hospital use

vasodilators crisis

Some remarks for antihypertensive drug classes

ACE-inhibitors: -effective and well tolerated

- reduce mortality also of dialysed patients (age < 65 yrs) independently

from the antihypertensive effect

- can reduce the synthesis/secretion of erythropoietin (anemia !)

- can trigger an anaphylactoid reaction in patients dialyzed with

AN69 dialyzer

PHARMACOKINETIC PROPERTIES OF ACE

INHIBITORS IN ESRD

T1/2(h)

normal

T1/2(h)

ESRD

Initial

dose in

HD

Maintenance

dose in HD

Removal

during HD

Captopril 2-3 20-30 12.5 q24h 25-50 q24h Yes

Enalapril 11 prolonged 2.5 q24h

or q48h

2.5-10 q24h

or q48h

Yes

Fosinopril 12 prolonged 10 q24h 10-20 q24h No

Lisinopril 13

54 2.5 q24h

or q48h

2.5-10 q24h

or q48h

Yes

Ramipril 11 prolonged 2.5-5q24h 2.5-10 q24h yes

Henrich W. Principles and Practice of Dialysis


ARB: - limited experience

- losartan does not enhance the risk of anaphylactoid dialyzer-reactions

- no dose adjustment is necessary in renal failure in the absence of

volume depletion.

PHARMACOKINETIC PROPERTIES OF ARB’S IN ESRD

T1/2(h)

normal

T1/2(h)

ESRD

Initial dose

in HD

Maintenance

dose in HD

Removal

during HD

Candesartan 9 ? 4 q24h 8-32 q24h No

Irbesartan 11-15 11-15 75-150 q24h 150-300 q24h No

Losartan 2 4 50 q24h 50-100 q24h No

Telmisartan 24 ? 40 q24h 20-80 q24h No

Valsartan 6 ? 80 q24h 80-160 q24h No



CCB: - effective and well tolerated

- do not require supplementary post dialysis dosing

-26 % (significant) reduction in cardiovascular mortality

in USRDS Study

BBL: - side effects include CNS depression (mainly lipid-soluble drugs),

bradycardia, and heart failure

- preferable beta-blocker may be atenolol, labetalol, carvedilol

PHARMACOLOGIC PROPERTIES OF Β-BLOCKERS IN

CHRONIC DIALYSIS PATIENTS

T1/2(h)

normal

T1/2(h)

ESRD

Initial dose

in HD

Maintenance

dose in HD

Removal

during HD

Bisoprolol 9-12 18-24 5 q24h

1.25 in HF

5-10 q24h

1.25-10 in HF

No

Atenolol 6-9 <120 25 q24h 25-50 q24h Yes

Carvedilol 4-7 4-7 12.5 od, b.i.d 12.5-50 od,

b.i.d

No

Metoprolol 3-4 3-4 50 b.i.d. 50-100 b.i.d. No

Propranolol 2-4 2-4 40 b.i.d. 40-80 b.i.d. No

Labetalol 4-8 4-8 50 bid 50-800 bid,

t.d.s, q.i.d

No



ABL: - Prazocin, Doxazocin

- help counteract the increase in sympathetic nerve activity.

- on long-term treatment the favourable metabolic effects

on lipids and insulin resistance might be advantageous.

- preferred mostly in antihypertensive combinations.

Centrally acting drugs: - methyldopa, clonidine, guanfacine have more side effects,

- moxonidine, rilmenidine (imidazoline I1 receptor agonists are safe

and effective, but only limited experience is available).

Special situations

Erythropoietin (EP)-induced hypertension - decrease the actual dry weight

- decrease the dose (if possible)of EP or interrupt treatment

- reintroduce treatment later at lower dose

- introduce or increase antihypertensive medication with preference

of CCB

Ribstein J, Mourad G, Argiles A et al. Hypertension in end-stage renal failure. In Complications of Dialysis.

Ed. by Lameire N, Mehta RL. Marcel Dekker, Inc. New York, USA, 2000. pp 274-287.

Special situations

Diabetic dialysis patients Characteristics

- the number of T2DM is rapidly increasing

- patients are generally hypertensive

- exchangeable sodium is increased

- frequent:

- orthostatic hypotension due to autonomic neuropathy with

severe symptoms

- coronary artery disease

- peripheral atherosclerosis

Special situations

Diabetic dialysis patients cont.

Treatment

To avoid the risk of severe hypotension:

- longer dialysis

- slow ultrafiltration rate

- hemofiltration

- glucose-containing dialysate can be used.

- ACE inhibitors and/or ARBs may prevent end-organ vascular

diseases

- CCBs are very effectively reduce blood pressure but may result in

severe hypotensive episodes

- BBL-benefit is particularly significant in patients with CHD

• Blood pressure remaining above goal in spite

of concurrent use of 3 antihypertensive agents of

different classes.

Resistant Hypertension

CLINICAL MARKERS FOR RESISTANT HYPERTENSION:

Advancing age

High base line blood pressure

Obesity and over weight

Excessive dietary salt intake, alcoholism

Chronic kidney disease

Diabetes mellitus type 2

Left ventricular hypertrophy

Black race

Female gender

RESISTANT HTN IN ESRD TREATMENT

Transdermal clonidine at weekly intervals.

Minoxidil, a potent vasodilator,

used with beta blockers

Spironolactone in Hemodialysis Patients

25-50 mg post dialysis

Risk of hyperkalemia

Improve EF and Improve BP control

Large studies are done

RESISTANT HYPERTENSION

The use of non steroidal anti-inflammatory drugs

Renovascular hypertension

Increasing cysts in polysystic kidney disease

Compliance

PSEUDORESISTANCE

Pseudo hypertension

Non-adherence may account for up to 50% of resistant cases

Inadequate Regimen

Especially inadequate diuretic component (pre-dialysis state)

Interfering medicines and substances also need to be considered

NSAIDs

Excessive Alcohol, Caffeine, or Tobacco

Excessive Salt Intake

Drugs of Abuse

Oral contraceptives

PSEUDOHYPERTENSION

Calcification of the arteries resulting in failure of the BP cuff to compress and occlude flow

Suspect if:

severe hypertension by cuff but no end organ injury

Antihypertensive excess results in symptoms/signs of Hypoperfusion/hypotension without measurable hypotension

Pipe stem calcification on x-ray

PSEUDOHYPERTENSION

Osler’s Maneuver (the radial artery remains palpable due to calcification and thickening despite inflation of cuff above systolic pressure) Poorly reproducible

“Dynamap”-like devices may be more accurate in this setting

Direct Intra-arterial measurement is the only definitive way to establish the diagnosis, but this is uncommonly done

RESISTANT HTN IN ESRD

Renal sympathetic nerve ablation

Hyperactivation of the sympathetic nervous system

J Clin Hypertens (Greenwich). 2012 Nov;14

The Future?

Device-Based Therapy for Resistant Hypertension

Baroreflex Activation Therapy

Renal Denervation Therapy

BAROREFLEX ACTIVATION THERAPY (BAT) CONTINUOUSLY MODULATES THE AUTONOMIC NERVOUS SYSTEM

Carotid Baroreceptor Stimulation

Heart Vessels Kidney

Inhibit sympathetic & Enhance Parasymp

HR Vasodilation Natriuresis

Renin

secretion

ANATOMICAL LOCATION OF RENAL SYMPATHETIC NERVES

Arise from T10-L1

Follow the renal artery to the kidney

Primarily lie within the adventitia

The Journal of Clinical Hypertension. 14, pages 799–801,2012

Circulation. 2002;106:1974–1979

Special features of frequently used

antihypertensive drugs in hemodialysis patients

Diuretics -avoid thiazide-type drugs, K-sparing drugs (amiloride, spironolactone)

acetazolamide

- furosemide is useful but it has ototoxicity and augment

aminoglycoside-toxicity

BBL - no change in the dose of carvedilol, labetalol, metoprolol, pindolol,

propranolol (active metabolites!), tertatolol, timolol

ACEi - fosinopril has dual excretion (50% kidney, 50% liver), therefore no

need to reduce the dose

Special features of frequently used

antihypertensive drugs in hemodialysis patients

ARBs - no need to change the dose of irbesartan, losartan, olmesartan,

telmisartan and valsartan

CCB - DHP-CCB: no need to change the dose

- verapamil: the dose should be reduced by 50 % (active metabolites!)

Direct vasodilators - no need to change the dose of diazoxide, hydralazine, minoxidil

- nitroprusside-Na: thiocyanate is dialysable

Antihypertensive drugs in dialysis patients Summary (when – which drug)

Cliniucal situation Drugs of choice Not recommended

CHF ACEi, ARB, BBL -

Post-MI ACEi, BBL Dir. vasodil.

LVH diast.dysf. BBL, dilti., verap. Dir. vasodil., α1BL

COPD ACEi, ARB, CCB BBL

CHD BBL, ACEi, CCB

ARB

Locatelli F. et al. Nephrol. Dial. Transoléant. 2004; 19:1058-1068

INTRADIALYTIC HYPERTENSION:

DEFINITIONS An increase in mean arterial blood pressure (MAP) ≥ 15 mmHg during or immediately after hemodialysis

An increase in systolic BP (SBP) >10 mmHg from pre

to postdialysis

sustained increase of BP during the dialysis session with BP values during and at the end of the dialysis session exceeding BP values at dialysis onset

Hypertension during the second or third hour of

hemodialysis after significant ultrafiltration has taken

place

An increase in BP that is resistant to ultrafiltration

Inrig JK. Intradialytic hypertension: a less-recognized cardiovascular complication of hemodialysis. Am

J Kidney Dis. 2010 March ; 55(3): 580–589 Chazot C and Jean G. Intradialytic hypertension: It is time to act. Nephron Clin Pract 2010;115:c182–c188

INTRADIALYTIC HYPERTENSION

5-15%

Mechanism

Extracellular volume overload

Increased cardiac output

Changes in sodium levels

Activation of the renin–angiotensin–aldosterone system

Overactivity of the sympathetic nervous system

Endothelial cell dysfunction.

Removal of anti HTN during dialysis

INTRADIALYTIC HYPERTENSION

The most important treatment is adequate sodium and water removal and reducing sympathetic hyperactivity.

Changing to non-dialyzable antihypertensive medications

Altering the dialysis prescription.

THANK YOU FOR YOUR ATTENION

Health & Medicine

Hyertension in patients on regular hemodialysis