Epidemiology of Interdialytic Ambulatory Hypertension and the Role of Volume Excess.
Editor's Note: Dr. Rajiv Agarwal is Professor of Medicine, Division of Nephrology, Indiana University Indianapolis, Indiana. USA. Rajiv is an internationally recognized leader in the area of clinical and translational research in nephrology. His foremost contribution has been in the area of hypertension in hemodialysis patients for which he receives funding from the National Institutes of Health. A summary of the topic can be obtained by clicking the Link. A more general review is available in his CJASN publication published in 2009. Rajiv has refined the techniques to diagnose and treat hypertension in this complex group of patients. Here he discusses his recent publication (published online Sep 2, 2011) in the American Journal of Nephrology.
2. Challenge their dry weight if BP is found to be elevated. Don't just add more antihypertensive agents to get the BP down. It may not work as well.
3. Beware of ESAs-they can raise BP. This study does not prove it but the package insert of ESAs states so. Mechanisms of increased BP with epoetin include enhanced responsiveness to norepinephrine and both an increase in endothelin-1 and constrictor prostanoids.
COMMENTARY
BP measurements before and after dialysis are dramatically different and these peridialytic measurements may not reflect recordings during the interdialytic interval. However, almost all studies have described the epidemiology of hypertension using BP recordings that are either measured immediately before or after dialysis. We performed our study (1) with two aims:
1. To describe the epidemiology of hypertension using 44-hour interdialytic ambulatory BP measurements.
2. To assess the association of volume excess with BP control.
This association was assessed in two ways. First, the relationship between hypertension control and ECF volume using echocardiographic evidence of volume excess is established. Second, antihypertensive medications among those with hypertension are gradually withdrawn to test whether an expanded ECF volume is associated with development of hypertension using 44-hour interdialytic ambulatory BP recordings.
Results related to epidemiology
We observed that among 369 ESRD patients on chronic hemodialysis the following:
1) Ambulatory BP defined hypertension (average systolic BP of 135 mm Hg or more and/or diastolic BP of 85 mm Hg or more, or the use of antihypertensive medications) was prevalent in the vast majority of patients: 82%.
2) Hypertension was independently associated with epoetin use, lower body mass index and fewer years on dialysis.
3) Although most of the patients were being treated (89%), hypertension was controlled adequately in only about a third (38%).
4) Poor control was independently associated with greater antihypertensive drug use.
Results related to volume excess
Inferior vena cava diameter in expiration is commonly regarded as a marker of excess ECF volume. The parameter was associated with increased risk of poorly controlled hypertension both in cross sectional analysis and after withdrawal of antihypertensive drugs. Thus volume excess was associated with poor BP control.
The association of fewer years on dialysis with greater hypertension has also been seen in many other studies and could be due to several reasons.
1) Survival bias-- it is possible that those with more hypertension die; therefore, the survivors have lower BP.
2) ESRD is state of chronic catecholamine excess (lack of renalase in part). Chronic catecholamine excess may lead to beta-adrenergic receptor down-regulation in long-term survivors.
Why was a lower body mass index independently associated with a greater prevalence of hypertension? Again there are several possibilities:
1) ECF volume excess may evoke a greater hemodynamic response in those who are lean. Obese people may have a greater buffer to sequester ECF volume which may dampen the hemodynamic response.
2) Skeletal muscle is an important site for renalase expression, an enzyme that breaks down catecholamines. Sarcopenic patients would therefore have greater circulating catecholamines and therefore greater BP.
What is the take home message?
1. Assess BP more often at home of dialysis patients (I recommend home BP monitoring).
2. Challenge their dry weight if BP is found to be elevated. Don't just add more antihypertensive agents to get the BP down. It may not work as well.
3. Beware of ESAs-they can raise BP. This study does not prove it but the package insert of ESAs states so. Mechanisms of increased BP with epoetin include enhanced responsiveness to norepinephrine and both an increase in endothelin-1 and constrictor prostanoids.
References
1. Agarwal R. Epidemiology of Interdialytic Ambulatory Hypertension and the Role of Volume Excess. Am J Nephrol. 2011 Sep 2;34(4):381-390.
