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 #
5U01DK062402-11
Application #
8242841
Study Section
Special Emphasis Panel (ZDK1-GRB-N (O1))
Program Officer
Flessner, Michael Francis
Project Start
2002-08-15
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
11
Fiscal Year
2012
Total Cost
$783,144
Indirect Cost
$374,107
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
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Braun, William E; Abebe, Kaleab Z; Brosnahan, Godela et al. (2018) ADPKD Progression in Patients With No Apparent Family History and No Mutation Detected by Sanger Sequencing. Am J Kidney Dis 71:294-296
Brosnahan, Godela M; Abebe, Kaleab Z; Rahbari-Oskoui, Frederic F et al. (2017) Effect of Statin Therapy on the Progression of Autosomal Dominant Polycystic Kidney Disease. A Secondary Analysis of the HALT PKD Trials. Curr Hypertens Rev 13:109-120
Torres, Vicente E; Abebe, Kaleab Z; Schrier, Robert W et al. (2017) Dietary salt restriction is beneficial to the management of autosomal dominant polycystic kidney disease. Kidney Int 91:493-500
Irazabal, María V; Abebe, Kaleab Z; Bae, Kyongtae Ty et al. (2017) Prognostic enrichment design in clinical trials for autosomal dominant polycystic kidney disease: the HALT-PKD clinical trial. Nephrol Dial Transplant 32:1857-1865

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