Both the diagnosis and treatment of hypertension in these patients can be a challenge
The characteristics of hypertension in hemodialysis patients differ from those in the general population. In dialysis patients, accelerated age-related changes in vascular stiffness, combined with factors peculiar to uremia, contribute to a loss of large and small vessel distensibility.
There are also changes in circulatory function, including an increase in systolic BP and widening of the pulse pressure. Systolic hypertension with or without diastolic hypertension is common in dialysis patients and associated with increased mortality risk. Isolated diastolic hypertension is rare in these patients, and diastolic BP is inversely related to cardiovascular risk in those with systolic hypertension (Semin Dial. 2003;16:208-213).
Hypertension (defined as mean predialysis systolic BP greater than 150 mm Hg, or diastolic BP greater than 85 mm Hg, or the use of antihypertensive medications) is found in about 86% of clinically stable, adult hemodialysis patients.
In contrast to the prevalence in the general population, the prevalence of hypertension in dialysis patients does not increase linearly with age, and is not influenced by sex or ethnicity. Hypertension is adequately controlled only about 30% of the time in these patients (Am J Med. 2003;115:291-297).
BP and prognosis
The association between predialysis BP and mortality risk in chronic hemodialysis patients has been controversial. Some studies have shown that higher BP in these patients offers a survival advantage. This counterintuitive relationship appears, in part, to be related to the methods of data analysis.
An inverse relationship between BP and total and cardiovascular mortality is ob-served when data are analyzed with systolic or diastolic BP as separate models. When both systolic and diastolic BP are considered together, systolic BP becomes a primary risk factor in predicting cardiovascular events in dialysis patients while diastolic BP retains the in-verse relationship (Kidney Int. 2005; 67:1-13).
The role of predialysis BP as a risk factor for mortality was examined in a random sample of 4,499 hemodialysis patients (Am J Kidney Dis. 1999;33:507-517). Low predialysis systolic BP (less than 100 mm Hg) was associated with an 86% increased mortality risk, and the relationship was strongest in patients with congestive heart failure. Pre-dialysis systolic hypertension was associated with an increased risk of cerebrovascular death but not total mortality. Postdialysis systolic BP was associated with an increased mortality risk for both low and high BP levels as compared with mid-range levels.
Systolic BP during the maintenance phase, corrected by hemodialysis, appears to play an important role in determining the patients’ prognoses. The relationship between BP and prognosis was studied in 195 patients new to dialysis (Am J Kidney Dis. 1995;25:405-412). In 46 who died within three years after starting dialysis, systolic BP was higher in both the introduction and maintenance phases than in the patients who survived more than three years.
There were no significant differences in diastolic BP during either phase between the survivors and nonsurvivors. The cumulative survival rate was similar in patients whose systolic BP was greater than 160 mm Hg during the introduction phase but decreased to below 160 mm Hg during the maintenance phase and in those whose systolic BP was below 160 mm Hg during both phases; the survival rate of both groups was significantly greater than that of patients whose systolic BP was greater than 160 mm Hg during both phases.
BP readings obtained in the hemodialysis unit are often used in therapeutic decision-making and to predict prognosis, but these values correlate poorly with ambulatory BP readings. Sources of BP mea-surement error in hemodialysis patients include interdialytic weight gain, the occurrence of sleep apnea and consequent nocturnal hypertension, and the inability to obtain BP readings in both arms in patients with hemodialysis angioaccess in the arm.
The problem is compounded by a lack of standardized BP measurements in these patients and the white coat effect. Precise measurement of BP in hemodialysis patients requires interdialytic ambulatory BP monitoring (Semin Dial. 2002;15:299-304). When this is not possible, BP values obtained in the hemodialysis unit can be used to identify the presence or absence of hypertension but cannot reliably predict ambulatory BP values in individual patients.
A two-week averaged predialysis BP greater than 150/85 mm Hg or a postdialysis BP greater than 130/75 mm Hg has at least 80% sensitivity in the diagnosis of hypertension (Kidney Int. 2006;69:900-906). Specificity of at least 80% can be achieved if predialysis BP greater than 160/90 mm Hg or postdialysis BP greater than 140/80 mm Hg is used. Predialysis BP is superior to postdialysis BP as a screening tool for detecting hypertension in dialysis patients.
Dietary sodium restriction and individualization of dialysate sodium delivery are useful initial steps. Predialysis plasma sodium content is relatively constant, and higher dialysate sodium concentrations may promote increased interdialytic fluid ingestion, weight gain, and BP. Compared with the use of standard dialysate, the use of low-sodium dialysate formulated in accord with the patient’s average predialysis plasma sodium level is associated with significant decreases in inter-dialytic weight gain, thirst scores, and episodes of hypotension (Kidney Int. 2004;66:1232-1238). In those with uncontrolled BP at baseline, the use of individualized dialysate is associated with significantly lower predialysis BP.
Increased frequency of dialysis may improve BP control and other cardiovascular endpoints in hypertensive patients. Compared with standard thrice-weekly sessions, short daily treatment is associated with significant decreases in 24-hour BP and left ventricular mass index. Daily sessions also increase the likelihood of withdrawing antihypertensive therapy in patients with ESRD who were stable on standard dialysis for at least six months (Am J Kidney Dis. 2001;38:371-376).
The beneficial effects may be related to decreases in extracellular water content. Supervised therapy with atenolol or lisinopril has proven safe and effective in controlling hypertension in dialysis patients. Those treated with atenolol three times weekly following dialysis achieved significant reductions in mean 44-hour interdialytic ambulatory BP without any increase in intradialytic hypotensive episodes or changes in serum glucose or potassium levels (Kidney Int. 1999;55:1528-1535). Treatment with lisinopril three times weekly following dialysis is associated with a significant and sustained decrease in the mean 44-hour interdialytic ambulatory BP (Am J Kidney Dis. 2001;38:1245-1250).
Nocturnal dialysis is a novel therapy that appears to improve BP control. A group of 28 patients were switched from conventional to nocturnal treatment and followed for a mean of 3.4 years (Kidney Int. 2002;61:2235-2239). They achieved significant reductions in systolic and diastolic BP, pulse pressure, left ventricular mass index, and the number of prescribed antihypertensive medications. Postdialysis extracellular fluid volumes were similar during conventional and nocturnal dialysis.
Dr. Agarwal is associate professor of clinical medicine in the division of nephrology at the Indiana University School of Medicine in Indianapolis.