This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term objective of this research is to reduce the morbidity and mortality of autosomal dominant polycystic kidney disease (ADPKD). This study is a 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, which reflects an increased number and size of renal cysts, as determined by ultrasonography. Secondary aims are: 1) to evaluate the effect of intensive blood pressure control on left ventricular mass index, on microalbuminuria, and on the activation level of several growth-related and inflammatory cytokines; and 2) to compare measurement of renal volume by ultrasonography and magnetic resonance imaging (MRI). 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 below 50th percentile and standard control as lowering blood pressure 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 below 50th percentile or to no treatment. 3. Normotensive subjects (blood pressure between the 25th and 75th percentile) with severe ADPKD (SADPKD, defined as > 10 renal cysts) will be randomized to treatment with ACEI or to no treatment. The first-line drug for all groups is enalapril. Second-line drugs for groups 1 and 2 are amlodipine, metoprolol, and hydrochlorothiazide. The primary outcome variable is the increase in renal volume per year, compared between the different blood pressure levels or between ACEI treatment and no treatment. If intensive blood pressure control or treatment with ACEI 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 enlarged kidneys and with end-stage renal disease in ADPKD.
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