The HALT-PKD study is the first prospective clinical interventional study for autosomal dominant polycystic disease (ADPKD). The goal of the HALT PKD study is to slow or prevent the progression of the kidney and heart disease in patients with early (Study A) or later (Study B) ADPKD. The focus of the HALT-PKD study is to block the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney and heart. Because of the local effects of the cysts on the kidney, the circulating and intrarenal RAAS is stimulated in ADPKD patients. The activation of the RAAS results in several consequences which have the potential to increase progression of kidney and heart complications in ADPKD. These include (1) raising blood pressure, (2) increasing kidney and heart fibrosis, (3) increasing oxidant injury of kidney and heart, (4) increasing growth factors which can stimulate increase proliferation of kidney cysts, and (5) increase remodeling of heart which predisposes to heart failure, heart attacks, and heart arrhythmias. There are substantial results demonstrating early hypertension and activation of the RAAS in subjects with ADPKD. Subjects with ADPKD will be separated into two groups based on renal function and age. Group A (Glomular Filtration Rate or GFR >60 ml/min/1.73 m2, ages 15 to 49 years) and Group B (GFR 30-60 ml/min/1.73 m2, ages 18 to 64 years). Group A subjects will be randomized in a 2-by-2 design to treatment with an Angiotensin Converting Enzyme Inhibitor (ACE-1) and an Angiotensin Receptor Blocker (ARB) versus an ACE-I plus placebo medication and to Standard (<130/80 mm Hg) or Rigorous (<110/75 mm Hg) blood pressure control. Study A primary endpoint is the percent change in total kidney size as measured by Magnetic Resonance Imaging (MRI). Study B subjects will be randomized to treatment with a combination of ACE-I/ARB therapy or ACE-I therapy alone, with both groups treated to Standard levels of blood pressure control (<130/80 mm Hg). The primary endpoint for Study B is a composite endpoint of time to the 50% reduction of baseline eGFR, eGFR <20 ml/min/1.73 m2, end stage renal disease (ESRD) or death.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01DK062402-12S1
Application #
8796343
Study Section
Special Emphasis Panel (ZDK1-GRB-N (O1))
Program Officer
Flessner, Michael Francis
Project Start
2002-08-15
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2015-01-31
Support Year
12
Fiscal Year
2014
Total Cost
$89,230
Indirect Cost
$31,585
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Torres, Vicente E; Abebe, Kaleab Z; Chapman, Arlene B et al. (2014) Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med 371:2267-76
Miskulin, Dana C; Abebe, Kaleab Z; Chapman, Arlene B et al. (2014) Health-related quality of life in patients with autosomal dominant polycystic kidney disease and CKD stages 1-4: a cross-sectional study. Am J Kidney Dis 63:214-26
Schrier, Robert W; Abebe, Kaleab Z; Perrone, Ronald D et al. (2014) Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med 371:2255-66
Torres, Vicente E; Chapman, Arlene B; Perrone, Ronald D et al. (2012) Analysis of baseline parameters in the HALT polycystic kidney disease trials. Kidney Int 81:577-85
Schrier, Robert W (2011) Hypertension and autosomal dominant polycystic kidney disease. Am J Kidney Dis 57:811-3
Perrone, Ronald D; Abebe, Kaleab Z; Schrier, Robert W et al. (2011) Cardiac magnetic resonance assessment of left ventricular mass in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 6:2508-15
Chapman, Arlene B; Torres, Vicente E; Perrone, Ronald D et al. (2010) The HALT polycystic kidney disease trials: design and implementation. Clin J Am Soc Nephrol 5:102-9
Ecder, Tevfik; Schrier, Robert W (2009) Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease. Nat Rev Nephrol 5:221-8
Schrier, Robert W (2006) Optimal care of autosomal dominant polycystic kidney disease patients. Nephrology (Carlton) 11:124-30