verbatim): The long-term objective of this research is to reduce the morbidity and mortality of autosomal dominant polycystic kidney disease (ADPKD). This project is an on-going 5-year clinical trial to test the hypothesis that intensive blood pressure control with angiotensin converting enzyme inhibitors (ACEI) as first-line drugs will slow the progression of ADPKD in children. Progression in children will be measured by increase in renal volume as determined by ultrasound imaging, reflecting increased number and size of renal cysts. Secondary aims are to evaluate the effect of intensive blood pressure control on left ventricular mass index, on microalbuminuria and proteinuria, and on the activation level of several growth-related and inflammatory cytokines. Three groups of children and young adults, age 4 to 21 years, will be randomized to different treatments: 1. Hypertensive subjects with blood pressures above the 95th percentile for age-, gender- and height-matched children will be randomized to intensive or standard blood pressure control, with intensive control defined as lowering blood pressure to the 45th to 50th percentile and standard control as lowering blood pressure to the 85th to 90th percentile. 2. Borderline hypertensive subjects with blood pressures between the 75th and 95th percentile will be randomized to treatment to lower the blood pressure to the 45th to 50th percentile versus no treatment. 3. Normotensive subjects (blood pressure between the 25th and 75th percentile) will be randomized to treatment with ACEI as long as blood pressure stays above the 25th percentile versus no treatment. The first-line drug for all groups is enalapril, second-line drugs for groups 1 and 2 are amlodipine and hydrochiorothiazide. The primary outcome variable is the increase in renal volume per year, compared between the different treatment levels or between treatment and no treatment. If intensive blood pressure control can be shown to reduce progressive renal enlargement, it would change screening and treatment recommendations for children from ADPKD families, and would have a major impact on the morbidity associated with large kidneys and with end-stage renal disease in ADPKD.
