There are over 316,000 patients with end-stage renal disease in the USA that cost Medicare about $11 billion/year. Hypertension plays an important role in causing excess cardiovascular morbidity and mortality that accounts for approximately half of all deaths, yet hypertension is poorly controlled in the vast majority of the US hemodialysis patients. There are no guidelines for the diagnosis and treatment of hemodialysis hypertension. We have preliminary evidence that home BP monitoring can accurately diagnose hypertension and that ultrafiltration and supervised antihypertensive drug therapies can enhance hypertension control.
In Specific Aim 1 we will evaluate the clinical performance of routine hemodialysis unit BP monitoring and home BP monitoring in the diagnosis of hemodialysis hypertension in 150 chronic hemodialysis patients. Interdialytic ambulatory BP will be the gold standard.
In Specific Aim 2 we hypothesize that achieving """"""""dry-weight"""""""" controls systolic hypertension rapidly in a prevalent hemodialysis cohort, can be predicted by echocardiographic signs of volume overload and can be accurately detected by home BP monitoring. This improvement in BP can be also predicted by demographic factors and parameters of volume excess. We propose an 8-week, prospective, randomized, trial of ultrafiltration therapy, to assess the efficacy, safety and tolerance of ultrafiltration therapy in controlling systolic hemodialysis hypertension. To assist clinicians in decision making, specific markers of volume excess such as plasma BNP (brain natriuretic peptide), plasma renin activity, and change in protein concentration from pre to post dialysis will be evaluated as predictors of improvement in BP with ultrafiltration therapy.
In specific aim 3 we hypothesize that an initial strategy of treatment with an ACE inhibitor based therapy is more effective than beta-blocker based therapy in causing regression of echocardiographic left ventricular hypertrophy (LVH) in patients with hemodialysis hypertension. We propose a parallel group, active control, randomized controlled trial comparing the safety and efficacy of initial monctherapy with an ACE inhibitor versus a beta-blocker each administered three times weekly after dialysis to assess BP reduction and LVH regression by echocardiography. In summary, we use simple strategies to diagnose hypertension in hemodialysis patients, evaluate the role of expanded extracellular fluid volume and test supervised drug therapies to impact hypertension control. We also assess the clinical performance of bedside tests to assess an expanded extracellular fluid space. Evaluation of such strategies will improve BP control in hemodialysis patients and, in the long-term, provide cardiovascular protection.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZRG1-CCVS (01))
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Eggers, Paul Wayne
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Indiana University-Purdue University at Indianapolis
Internal Medicine/Medicine
Schools of Medicine
United States
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Georgianos, Panagiotis I; Agarwal, Rajiv (2018) Blood pressure control in conventional hemodialysis. Semin Dial 31:557-562
Sinha, Arjun D; Agarwal, Rajiv (2017) Setting the dry weight and its cardiovascular implications. Semin Dial 30:481-488
Agarwal, Rajiv (2016) Treating hypertension in hemodialysis improves symptoms seemingly unrelated to volume excess. Nephrol Dial Transplant 31:142-9
Georgianos, Panagiotis I; Agarwal, Rajiv (2015) Relative Importance of Aortic Stiffness and Volume as Predictors of Treatment-Induced Improvement in Left Ventricular Mass Index in Dialysis. PLoS One 10:e0135457
Georgianos, Panagiotis I; Agarwal, Rajiv (2015) Effect of lisinopril and atenolol on aortic stiffness in patients on hemodialysis. Clin J Am Soc Nephrol 10:639-45
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) B-type natriuretic peptide is not a volume marker among patients on hemodialysis. Nephrol Dial Transplant 28:3082-9
Agarwal, Rajiv (2013) Salt, salt sensitivity, and the endothelium: a pathway to discovery of molecular mechanisms. Hypertension 62:831-3

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