SICU Conference

Hypertension in End-Stage Renal Disease Patient

Ri 彭偉倫

Hypertension and ESRD

Hypertension is a major cause of end-stage renal disease(ESRD)

Base on the 1997 United States Renal Data System report, the incidence rate of hypertension and diabetes mellitus as causes of ESRD continue to increase more rapidly than the other major causes of ESRD

Hypertension ESRD

Although poorly controlled hypertension may either cause or accelerate the development of renal failure, it can also be a sequence of renal disease

ESRD and Cardiovascular Disease

Cardiovascular disease is the leading cause of death in patients undergoing dialysis and renal transplantation

Atherosclerosic and cardiovascular disorders have been found to be more prevalent in dialysis patients than in the general population

Outcomes A number of studies have suggested poorer

outcomes in those patients with ESRD with uncontrolled hypertension

Two Japanese studies suggested that the early correction of elevated systolic pressure was important in determining the ultimate prognosis of the hemodialyzed patients

The patient groups with normal BP had better survival

Low Blood Pressure

Recent data have shown that abnormally low predialysis systolic blood pressure levels (<110mmHg) were associated with decreased survival on dialysis

Pathogenesis

Putative Pathogenetic Mechanisms of Hypertension in ESRD PatientsExpanded 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 egress, 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 increased 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

Treatment

It has been reported that hypertension is less well controlled in patients undergoing dialysis

In a large cohort of European hemodialysis patients treated for hypertension, it was reported that 87% of the patients with diabetes and 65% of the patients without diabetes had inadequate BP control

Volume Control

Volume control can either normalized the BP or make hypertension easier to control

Salt and water balance

Dialysis

Dry Weight(I)

Attaining dry weight will either normalized the BP or male it easier to control in 80% to 90% of patients

The absence of edema does not exclude the hypervolemia

It is the thorniest clinical problem of clinical nephrologists

Dry Weight(II) Not merely the absence of edema, but the body sodium

content and volume of body water or critical component thereof 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 and Water Balance

Patient compliance is often sub-optimal

As a result, heavy reliance is placed on the dialysis ultrafiltration 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

Dialysis

Two crossover studies and one long-term project demonstrated that more frequent and longer hemodialysis treatment were associated with normal blood pressures without medications and with regression of left ventricular hypertrophy

Antihypertensive drugs and rapid fluid removal required by shorter dialysis time may limit the degree of fluid removal

Antihypertensive Drugs(I) Antihypertensive drugs are indicated in patients in

whom hypertension persists, despite seemingly adequate volume control

Elevated BP can usually be controlled by most classes of antohypertensive agents

The selection of antohypertensive agents is frequently dictated by the presence of comorbid conditions

Antihypertensive Drugs(II)

One European study

Ca2+ channel blocker > ACEI > α blocker > β blocker

These agents are often prescribed in the evening, especially after dialysis

Antihypertensive Drugs(III)

The addition of antihypertensive drugs may make

dialysis more difficult to deliver and may lead to

the inability to control interdialytic hypertension,

dialysis-induced hypotension, and failure to

achieve dry weight

Ca2+ channel blockers

They are effective and well tolerated in dialysis patients

They may be particular useful in patients with LVH and diastolic dysfunction

Certain of these agents have a negative inotropic and negative chronotropic effect on the myocardium

Angiotension-Conveerting Enzyme Inhibitors (I)

Reduce the production of angiotensin II and also decrease degradation of vasodilating bradykinins and prostaglandins

They are well tolerated and are particularly effective in patients with a history of heart failure due to systolic dysfunction and may induce a more rapid regression of LVH

Angiotension-Conveerting Enzyme Inhibitors (II)

They may aggravate anemia by reducing the action

of erythropoietin

They can trigger an anaphylactoid reaction in

patients dialyzed with a PAN membrane dialyzer

Angiotension II receptor Antagonists

In a study of 89 patients of whom 20 were undergoing hemodialysis, BP responded well and no significant biochemical alternation were noted

They are not associated with altered kinin metabolism and are not expected to elicit anaphylactoid reaction to PAN membrane dialyzer

β blockers

They are particularly indicated in patients who have had a recent myocardial infarction or suffer from angina pectoris

Potential side effects include CNS depression, bradycardia, altered lipid profiles, hyperkalemia, altered response to hypoglycemia, and bronchospasm

α blockers

These agents are commonly used in patients who also have BPH

They have a favorable metabolic side effect profile Orthostatic symptoms may occur, especially in

older patiemts

Central Sympathetic Agonists

These agents, such as clonidine and nethyldopa,

are used less frequently because of their adverse

effects involving the central nervous system

Refractory Hypertension (I)

Some dialysis patients are resistant to both volume control and antihypertensive medications

Concurrent use of certain over-the-counter medication

Secondary hypertension

Refractory Hypertension (II)

If faced with refractory hypertension, the clinician should redouble his efforts to determine whether the patient is truly at dry weight

If a treatable cause cannot be found, minoxidil, in combination with a β blocker may be effective in reducing the BP

Blood Pressure Control

Lowering the blood pressure too rapidly may be hazardous

Blood pressure should be controlled in a gradual manner to allow for adaptation

Optimal Blood Pressure Level

The optimal blood pressure level may be best defined by the individual patient’s overall cardiovascular profile, including age, previous and concurrent complications, and comorbid diseases

Blood pressure should be maintained as close to normal as possibleBP < 135/85mmHg by dayBP < 120/80mmHg by night

Clinical Therapeutic Conclusions Withdraw slowly as many antihypertensive

medications as possible in the process of establishing a rational dry weight

Set a realistic timetable for attaining dry weight Once the dry weight has been established, if BP

remains elevated, it may be necessary to initiate or continue antihypertensive medication, but continue reassessing dry weight

Thank You For Your Attention