Tetrahydrobiopterin in Patients With Chronic Kidney Disease (CKD) and Albuminuria

• Patients with controlled hypertension (blood pressure (BP) less than 150/90 mmHg) using standard antihypertensive medications.
• Stable chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) 40-90 ml/min/173m2 by the abbreviated Modification of Diet in Renal Disease (MDRD) equation and with a rate of decline of eGFR no greater than 1ml/min/1.73m2 per month over the prior 3 months with albuminuria (urine albumin excretion in the 24-hr urine sample of between 300-3000mg).

• No concomitant use with:

  • Vitamin C supplements
  • Multivitamins containing vitamin C
  • Any other dietary supplements, nutraceuticals, or other over-the- counter products containing vitamin C
  • Vitamin E containing supplements
• Concurrently taking study approved antihypertensive medications at a stable dose for at least 3 months prior to screening.
• Sexually active subjects must be willing and able to use an acceptable method of contraception
• Females of childbearing potential must have a negative pregnancy test at screening. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to screening, or who have had total hysterectomy.

Exclusion Criteria:

• Uncontrolled hypertension with BP greater than 150/90 or with frequent changes to antihypertensive regimen during the last 3 months.
• Concurrent disease or condition that would interfere with study participation or safety, such as bleeding disorders, history of syncope or vertigo; severe gastroesophageal reflux disease (GERD) or gastric ulcers; heart failure; symptomatic coronary or peripheral vascular disease; arrhythmia; serious neurologic disorders, including seizures; or organ transplant.
• Diabetics that are uncontrolled, unstable, newly diagnosed, or have undergone major changes in therapy in the last three months or HbA1C consistently greater than 9.0.
• Any severe comorbid condition that would limit life expectancy to less than 6 months.
• Advanced stage III CKD or worse , i.e. eGFR less than 40 ml/min/1.73m2 (by abbreviated MDRD formula).
• History of nephrolithiasis.
• Patients with albuminuria due to causes other than hypertension and /or diabetes; e.g., systemic lupus erythematosus (SLE).
• Hepatic enzyme concentrations greater than 2 times the upper limit of normal.
• HIV infection, hepatic cirrhosis, other preexisting liver disease, or positive HIV, Hepatitis B or C test at screening.
• Concomitant treatment with drugs known to inhibit folate metabolism, Levodopa, phosphodiesterase (PDE) 5 inhibitors or PDE 3 inhibitors.
• Myocardial infarction, stroke, or surgery within the last 60 days prior to screening.
• History of alcohol and/or drug abuse.
• Pregnant or breastfeeding at screening, or planning to become pregnant (subject or partner) at any time during the study.
• Previous treatment with tetrahydrobiopterin (6R-BH4).
• Has known hypersensitivity to 6R-BH4 or its excipients.
• Any condition that, in the view of the principal investigator (PI), places the subject at high risk of poor treatment compliance or of not completing the study.