a translational approach to gitelman syndrome

Conditions: Gitelman Syndrome

Summary: this study will test the response to a single dose of thiazide diuretic as a diagnostic test for gitelman syndrome. individuals with hypokalemic alkalosis will be enrolled. after a baseline study, they will have the response to 50 mg hydrochlorothiazide on fractional chloride excretion examined.

the purpose of this study is to test the hypothesis that gitelman syndrome (gs) can be diagnosed using a simple clinical protocol. gs is an inherited kidney disease that usually shows up in patients as low blood potassium levels. currently, no commercial genetic test for gs exists. currently, gs is diagnosed based upon clinical findings but this method is not precise and often not reliable. thus, in order to develop new treatments specific for gs patients, a more exact method of diagnosis would be of benefit. eligible subjects are men and women ages 21-60 with normal blood pressure who have been diagnosed with low blood potassium of uncertain cause. subjects may withdraw at any time. this study requires 3 visits to ohsu's campus. study visit 1 will occur during a normal visit with the nephrologist. as part of the normal visit, a complete interview, physical exam and urine and blood samples will be taken. in addition, another blood sample will be taken and used for genetic analysis. a urine pregnancy test will be administered. a quality of life survey, described below, will be administered. the genetic analysis, urine pregnancy test and quality of life survey are not normal tests for gs. blood and urine samples, as well as pregnancy tests will be collected/administered at the oregon clinical and translational research institute (octri). during the intervention period, subjects will refrain from taking their potassium sparing medications for 7 days. this period is called the washout period and is needed to ensure that blood tests during the hydrochlorthiazide (hctz, a "water pill") (see below), are not affected by medications. on the 3rd day of the washout period, study visit 2 will occur at the octri. this will require blood to be drawn, to insure that subjects maintain proper blood levels of potassium and magnesium. magnesium and potassium supplements will be allowed during the washout. after review of the blood test results, the investigator may adjust the doses of these supplements in order to keep subject blood levels of potassium and magnesium as close to normal as possible. blood pressure, heart rate and breathing rate will also be checked at this visit. study visit 3 will occur at the octri and will be devoted to the hctz test. during the course of the hctz test, subjects will have an plastic tube (an iv) placed in an arm vein, have vital signs checked and receive 50mg of hctz to take by mouth . subjects will provide 8 urine samples and 3 blood samples. the time required for this visit is expected to be 6 hours. the total time required for subjects to complete the study from study visit 1 through discharge from the octri on study visit 3 will not be less than 9 days and subjects should not expect the total length to exceed three weeks depending on available appointments for study visit 3 at the octri. the quality of life survey is derived from a national research corporation and has been modified for use in this study. the authors of this survey allow free public use of this document provided it is properly referenced in any presentation of the study's results. hctz is an fda approved medication. there are no experimental drugs or devices used in this study. the purpose of this study is to develop methods for, and determine the feasibility of, performing a hctz test and genetic analysis for gs at ohsu. there is no statistical analysis of data, but descriptive characteristics will be entered into an access database with password restricted access. genetic samples will be analyzed using pcr and standard sequencing techniques. data and samples will be stored for a maximum of 15 years.

Eligibility criteria:
inclusion criteria: 1. institutional review board (irb) approved written informed consent and health insurance portability and accountability act (hipaa) authorization as per national regulations, must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 2. subject is between the ages of 21 and 60. 3. female subjects of child bearing potential must have a negative urine pregnancy test at the screening visit (study visit 1) and must agree to maintain effective birth control during the study. 4. subjects who are referred to dr. ellison for evaluation of normotensive hypokalemia of unknown etiology exclusion criteria: 1. subject has known allergy to thiazide or sulfonamide medications 2. subject is pregnant or lactating. 3. subject has major systemic illnesses that affect potassium regulation through pathology or pharmacologic treatment. this category includes: * hypertension * requiring regular pharmacological control * history of blood pressure greater than 140mmhg systolic and 90mmhg diastolic * congestive heart failure * cirrhosis of the liver 4. subject has documented kidney disease resulting in anuria, proteinuria or abnormal urinalysis, or requiring dialysis for treatment.

Keywords: hypokalemia bartter syndrome salt wasting