Uric Acid in Essential Hypertension in Children

The study will be a double-blinded crossover trial. We will recruit 40 children between the ages of 12 and 18 years, from the pediatric renal and hypertension programs at Texas Children's Hospital. The study consists of four phases, a screening phase a treatment phase, an interim washout phase and a crossover phase. The screening phase will last between 1 and 2 weeks. Patients will be provided with a digital blood pressure monitor with an appropriately sized cuff and be instructed to perform daily blood pressure measurements and keep a blood pressure log. This will detect severe hypertension that needs immediate attention and identify patients or families in which compliance problems likely to compromise data collection. Blood tests will be done to determine eligibility based on clinical laboratory parameters and 10ml of blood will be sent to the research laboratory for measurement of erythropoetin, ADMA, MCP-1 and possibly other modulators of vascular tone. Girls who are post-menarche will have a urine or serum pregnancy test. Prior to the initiation of any study procedures, informed consent and child assent (if appropriate) will be obtained from the participant and parents. Immediately prior to the initiation of the treatment or placebo phase 24-hour ambulatory blood pressure monitoring (ABPM #1) will be performed. Urinary nitrates and protein to creatinine ratio will be measured as surrogates for NOS activation and ongoing renal damage. At the end of the screening phase, eligible patients will be randomly assigned to either placebo or allopurinol for the active phase. Children will receive the other during the crossover phase. The purpose of this blinding is to remove either participant or investigator bias from the acquisition of the data. Active Phase: The active phase will last six weeks and include a clinic visit on the first day of the phase, laboratory testing between day 4 and 7, and telephone contact halfway through the phase. At the clinic visit, patients will receive their study medication (allopurinol or placebo) in a bottle prepared by the investigational pharmacy. Subjects on allopurinol will receive 10 mg/kg divided bid (maximum of 400mg). Laboratory tests will be performed 4 to 7 days after starting the medication to screen for hepatic or bone marrow toxicity (AST, ALT, CBC) and serum uric acid. Evidence for toxicity will cause un-blinding and withdrawal from the study. The families will also be instructed to continue the daily blood pressure log started in the screening phase. Twenty-four-hour ABPM and end of phase laboratory tests including, hemoglobin, serum uric acid, erythropoetin, ADMA, MCP-1 and urinary nitrates will be performed at the conclusion of the active phase, prior to discontinuing the study medication for the washout phase. Washout Phase: Upon completion of the ABPM at the end of the active phase, the study medication will be discontinued. The families will continue the home BP logs. The washout phase will end when either the child meets criteria for hypertension or two weeks have elapsed since completion of the previous phase. Crossover Phase: The crossover phase will identical in procedures to the active phase except that the medication will be that which was not previously received. Follow-up visit: Upon completion of both arms the subjects will have a final clinic visit. The laboratory tests will be repeated and if the third ABPM is not complete it will be initiated. Conventional antihypertensive therapy will be discussed and initiated if appropriate. Routine follow up will be established for management of the child's hypertension and other medical problems.