Metformin and Congenital Nephrogenic Diabetes Insipidus

Nephrogenic diabetes insipidus (NDI) is a genetic disease. Patients with this disease make large amounts of urine because their kidneys don't hold on to water. The large amount of urine means that patients need to urinate very frequently. They are also at increased risk for dehydration if they don't drink enough. The large amount of urine can sometimes damage their bladders and kidneys. There are some medicines that may help these patients urinate less, but they are not very effective. There is evidence in animal studies that a medication called metformin may help patients with NDI urinate less.

• Metformin (Drug), also known as Glumetza, Fortamet, Glucophage, Riomet: Metformin 500 mg pill dispensed once orally

Primary outcomes

• Change in mean urine osmolality [Baseline, 7 hours]: Urine osmolality is a measure of urine concentration. Urine osmolality will be measured using a Wescor vapor pressure osmometer. A normal range for urine osmolality is approximately 500-850 mOsm/kg water. Change is the difference in average osmolality from baseline to 7 hours.

Secondary outcomes

• Change in mean urine volume [Baseline, 7 hours]: Urine volume is a measure of fluid balance. Change from baseline in average volume of urine collected from baseline to 7 hours.

Sex: Male, ages: 18 Years to any

Inclusion Criteria:

* Males with a documented mutation in the vasopressin type 2 receptor (V2R)
* Willing to provide consent and/or assent as appropriate
* Capable of providing urine samples as dictated by the protocol

Exclusion Criteria:

* Urinary incontinence
* Subjects who have heart disease, liver disease, diabetes, cancer, or other significant disease other than Nephrogenic Diabetes Insipidus (NDI)
* Subjects with significant renal dysfunction (defined as a calculated glomerular filtration rate (GFR) <80 ml/min/1.73 m\^2)
* Subjects with acquired NDI

• Larry Greenbaum, MD, PhD, Principal investigator, Emory University
• Titilayo Ilori, MD, Principal investigator, Emory University