Controlled Trial of Renin Angiotensin Blockade in ADPKD

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DESCRIPTION (provided by applicant): The overall hypothesis of the proposed studies is that an intensified interventional strategy aimed at blocking the renin angiotensin system at multiple levels (angiotensin II-receptor interaction by an angiotensin II AT1-receptor blocker or ARB, angiotensin II generation by an angiotensin I converting-enzyme inhibitor or ACEI, an angiotensin II AT1-receptor density and intracellular signaling by inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase or statin) will slow down the progression of the renal cystic disease in patients with normal or near-normal renal function (GFR > 60ml/min/1.73m2) and the decline of renal function in patients with mild to moderate renal insufficiency (30-60 ml/min/1.73 m2) (Main Study) and that the success of this strategy will be predicted by the extent to which it corrects the intrarenal hemodynamic alterations associated with autosomal dominant polycystic kidney disease (ADPKD) (Pilot Study). The primary end-points for the Main Study will be a 15% increase in kidney volume or a 30% increase in cyst volume measured by MR in patients with normal or near-normal renal function and a 50% reduction in GFR or a doubling in serum creatinine in patients with mild to moderate renal insufficiency. MR determinations of renal blood flow (RBF), renal vascular resistance (RVR) and arterial compliance will be obtained to ascertain the extent to which the hemodynamic changes in response to therapeutic interventions can predict their success in delaying the progression of the renal cystic disease or the decline of renal function. Similar methodology will be used to ascertain the potential value of novel antihypertensive therapies in ADPKD. The protocols for the Main Study will be conducted in 500 patients, 250 recruited at the Mayo Clinic, 150 recruited at KUMC, and 100 at the Cleveland Clinic. Approximately one-half of these patients will have normal or near-normal renal function and one-half have mild to moderate renal insufficiency. The protocols for the Pilot Study will be conducted only at the Mayo Clinic.