The long-term goal of this project is to understand the utility of home BP monitoring in managing hypertension, role of volume overload in causing hypertension and drug therapy in the treatment of hypertension in hemodialysis patients. We hypothesize that that volume control can improve BP and antihypertensive therapy can regress left ventricular hypertrophy in long-term hemodialysis patients.
Specific aims : #1. In a randomized trial of 150 patients we have shown that volume control improves hypertension in hemodialysis patients within 4 weeks that persists at 8 weeks. To improve the diagnosis of hypertension, predict the response to ultrafiltration and explore the mechanisms of hypertension control in hemodialysis patients we propose 4 additional analyses on the data collected. #2. We propose to complete an ongoing randomized controlled trial of beta- blocker versus ACE-inhibitor based antihypertensive therapy in effecting regression of left ventricular hypertrophy. Methods:
Aim 1 of the application has 4 analyses which are as follows: 1. To support the use of home BP to diagnose and manage hypertension we will test the relationship of home BP improvement in the ultrafiltration group compared to controls and the agreement with improvement in ambulatory BP. We expect that the agreement between home BP and ambulatory BP will exceed the agreement between dialysis unit BP and ambulatory BP. 2. To uncover the markers of volume overload, we will evaluate a panel of markers that predict BP fall with ultrafiltration. We expect an improvement in ambulatory BP in the ultrafiltration group when patients are volume overloaded as defined by a panel of 4 markers. 3. To evaluate the value of ambulatory BP as a marker of volume overload, we will analyze the relationship of change in patterns of ambulatory BP in the ultrafiltration group compared to controls. We expect that the ultrafiltration group will have fundamental changes in patterns of ambulatory BP as assessed by the trended cosinor model. 4. To determine the contribution of arterial stiffness in causing hypertension, we will analyze the improvement in pulse wave velocity in response to ultrafiltration. We expect that ultrafiltration will lead to improvement in arterial stiffness and ambulatory BP.
Aim 2 of the application is a parallel group, active control, single-center, randomized open-label trial comparing the safety and efficacy of lisinopril vs. beta- blocker atenolol-based therapy each administered three times weekly after dialysis on the primary outcome variable of regression of echocardiographic left ventricular hypertrophy. BP control will be achieved by home BP recordings. Significance: Cardiovascular disease is the major cause of death in hemodialysis patients and hypertension a major contributor of cardiovascular disease. The strategies of diagnosis, management and treatment of hypertension in hemodialysis patients developed in this application when applied to a larger population of dialysis patients may result in improved BP control and better cardiovascular outcomes. Novelty: The volume index developed as a marker of excess volume and the trended cosinor model developed to analyze hemodynamic patterns in hemodialysis patients are novel discoveries from our earlier grant. Application of these novel models to randomized controlled trials would transform a mathematical expression to a live clinical tool.

Public Health Relevance

Cardiovascular mortality is the major cause of death in patients on hemodialysis. The long-term goal of this project is to understand the utility of home BP monitoring in managing hypertension, role of volume overload in causing hypertension and drug therapy in the treatment of hypertension in hemodialysis patients. We hypothesize that that volume control can improve BP and antihypertensive therapy can regress left ventricular hypertrophy in long-term hemodialysis patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK062030-10
Application #
8534091
Study Section
Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
Narva, Andrew
Project Start
2002-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
10
Fiscal Year
2013
Total Cost
$314,016
Indirect Cost
$107,697
Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Agarwal, Rajiv; Flynn, Joseph; Pogue, Velvie et al. (2014) Assessment and management of hypertension in patients on dialysis. J Am Soc Nephrol 25:1630-46
Sinha, Arjun D; Agarwal, Rajiv (2014) Hypertension Treatment for Patients with Advanced Chronic Kidney Disease. Curr Cardiovasc Risk Rep 8:
Sinha, Arjun D; Agarwal, Rajiv (2014) What are the causes of the ill effects of chronic hemodialysis? The fallacy of low interdialytic weight gain and low ultrafiltration rate: lower is not always better. Semin Dial 27:11-3
Agarwal, Rajiv (2013) Salt, salt sensitivity, and the endothelium: a pathway to discovery of molecular mechanisms. Hypertension 62:831-3
Tandon, Teena; Sinha, Arjun D; Agarwal, Rajiv (2013) Shorter delivered dialysis times associate with a higher and more difficult to treat blood pressure. Nephrol Dial Transplant 28:1562-8
Agarwal, Rajiv (2013) B-type natriuretic peptide is not a volume marker among patients on hemodialysis. Nephrol Dial Transplant 28:3082-9
Agarwal, Rajiv (2011) Epidemiology of interdialytic ambulatory hypertension and the role of volume excess. Am J Nephrol 34:381-90
Agarwal, Rajiv; Sinha, Arjun D; Light, Robert P (2011) Toward a definition of masked hypertension and white-coat hypertension among hemodialysis patients. Clin J Am Soc Nephrol 6:2003-8
Agarwal, Rajiv; Bouldin, J Michael; Light, Robert P et al. (2011) Inferior vena cava diameter and left atrial diameter measure volume but not dry weight. Clin J Am Soc Nephrol 6:1066-72
Agarwal, Rajiv (2011) Interdialytic hypertension-an update. Adv Chronic Kidney Dis 18:11-6

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