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.
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