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Hemodialysis Patients
C. Venkata S. Ram, MD, and Andrew Z. Fenves, MD
Corresponding author
C. Venkata S. Ram, MD
1420 Viceroy Drive, Dallas, TX 75235, USA.
E-mail: ramv@dneph.com
Current Hypertension Reports 2009, 11:292298
Current Medicine Group LLC ISSN 1522-6417
Copyright 2009 by Current Medicine Group LLC
Introduction
Systemic hypertension in patients undergoing chronic
dialysis presents a major therapeutic challenge in clinical
medicine. Because it is a cause as well as a consequence of
chronic kidney disease (CKD) and end-stage renal disease
(ESRD), hypertension not only is prevalent in patients
undergoing dialysis but also is a critical contributor to
excessive cardiovascular morbidity and mortality in these
high-risk patients. Hypertension occurs in more than 80%
of patients who have ESRD [1]. The prevalence and degree
of hypertension is steadily increasing in patients undergoing hemodialysis or chronic ambulatory peritoneal dialysis.
Pathophysiologic Factors
The etiology of hypertension in ESRD is complex and
multifactorial. With the establishment and progression of
hypertension in ESRD, the hemodynamic milieu changes
dramatically with complicated interactions among the
mechanisms of circulatory control. Because of the complex
interplay of various pathophysiologic processes, treatment
of hypertension in ESRD is extremely difficult and the
therapeutic response is often unpredictable. In a substantial number of patients on dialysis, removal of excess fluid
and achievement of dry weight improves blood pressure
control. Patients with ESRD demonstrate a rise in cardiac
output as a reaction to anemia. In normotensive patients
with ESRD, the rise in cardiac output is accompanied by
a fall in peripheral vascular resistance; in hypertensive
patients, however, this reciprocal adaptive change fails to
occur, culminating in a blood pressure rise. The discussion in this article applies to hemodialysis patients but
not to peritoneal dialysis patients, with some exceptions.
Blood pressure control in patients undergoing peritoneal
dialysis is less difficult than in hemodialysis patients.
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Erythropoietin use
Therapeutic application of recombinant human erythropoietin (rHuEPO) has been a significant advance in the
management of anemia in ESRD/hemodialysis patients.
Unfortunately, rHuEPO increases blood pressure by
causing vasoconstriction and increasing the blood viscosity (Table 2) [1416]; correction of anemia also prevents
hypoxia-mediated vasodilatation. The rise in blood pressure with the use of rHuEPO occurs within 2 to 12 weeks
of therapy. Rapid correction of anemia and a prior history of hypertension are important predisposing factors.
Both anemia and its overcorrection can be detrimental, so
every attempt should be made to keep the maximum level
of hemoglobin between 10 and 12 g/dL.
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Prostaglandins
Because renal prostaglandins and prostacyclin cause
vasodilatation, a deficiency of these mediators in ESRD
may increase blood pressure. They also offset vasoconstrictor influences. Hence, renal prostaglandins may play
a pathologic role in blood pressure regulation in patients
with ESRD.
Treatment of Hypertension
Divalent ions and parathyroid hormone
Intracellular levels of calcium are increased in patients
with chronic renal failure, and there is a direct pathophysiologic correlation between intracellular calcium and
blood pressure levels in dialysis patients with hypertension. Studies have shown a positive correlation between
intracellular and platelet calcium, serum parathyroid
hormone (PTH), and blood pressure levels in patients
with chronic renal failure [1719]. Hypercalcemia is more
likely to raise blood pressure in the presence of increased
PTH levels because of vasoconstriction, not cardiac output changes. Exogenous use of vitamin D analogues and
oral calcium supplementation are some factors contributing to hypercalcemia in ESRD. Augmentation of RAS and
SNS activity may also raise cytosolic concentrations of
calcium. Correction of hyperparathyroidism by vitamin
D administration or parathyroidectomy may lower blood
pressure in patients with ESRD. PTH appears to play a
role in the development of hypertension associated with
hypercalcemia in ESRD.
Endothelial factors
The role of endothelial cells in regulating vasomotor tone
and systemic vascular resistance is well established. The
availability and actions of endothelium-derived relaxation
factornow identified as nitric oxide (NO)governs the
state of vasoactive tone [20]. An absolute or relative deficiency of NO leads to a rise in the blood pressure level.
This mechanism may play a role in the development of
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Direct vasodilators
Despite the advent of effective dialysis and modern
antihypertensive drugs, some patients with ESRD have
a therapeutic need for old direct vasodilators such as
hydralazine and minoxidil to achieve their goal blood
pressure levels. Before the availability of RAS blockers
and CCBs, direct vasodilators were used extensively in
ESRD to control hypertension: both hydralazine and minoxidil, in conjunction with adequate volume control and
-blockade, lowered the blood pressure significantly.
Because of brisk stimulation of reflex SNS activity,
direct vasodilator therapy should be accompanied by
simultaneous -blockade to offset tachycardia. To minimize adverse effects, the total daily dose of hydralazine
should not exceed 200 mg. For all practical purposes,
minoxidil can be considered a more potent version of
hydralazine. It is a powerful vasodilator and is advocated for severe and resistant forms of hypertension. The
adverse-effect profi le of minoxidil is very similar to that
of hydralazine, with the addition of hair growth and
massive fluid retention (managed by ultrafi ltration). For
these reasons, the use of minoxidil is restricted. Despite
the complexities of using hydralazine and minoxidil, these
drugs have a practical role in the management of resistant
hypertension when they are used properly.
Secondary Hypertension
Secondary forms of hypertension should be considered
in the dialysis patient with resistant hypertension, based
upon clinical and laboratory parameters. Although
hypertension in patients with ESRD is generally
advanced and linked to the decline in renal function, a
secondary source (eg, renovascular or endocrine causes
or sleep apnea) should be pursued on clinical grounds
in selected patients. The extent of the workup should be
guided by the clinical course, patient characteristics, and
laboratory fi ndings.
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Acknowledgment
The authors thank Ms. Nanci Hassell for her assistance in
the preparation of this manuscript.
Disclosure
No potential confl icts of interest relevant to this article
were reported.
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