Nitrite-boosting Therapy for Improving Physiological Function in Patients With Chronic Kidney Disease

Inclusion Criteria: * CKD stage II-IV (eGFR using the Modification of Diet in Renal Disease (MDRD) prediction equation 20-90 mL/min/1.73m2; stable renal function in the past 3 months) * Ability to give informed consent * Albumin \> 3.0 g/dL * Ability to perform motor and cognitive tests (e.g., can rise from a chair, walk for 6 min, climb 10 stairs) * Free from alcohol dependence or abuse, as defined by the American Psychiatry Association, Diagnostic and Statistical Manual of Mental Disorders (DSM-V) * Mini-mental state examination score \>21 (rationale: to screen for subjects with major cognitive impairment) * Blood pressure (BP) \>100/60 mmHg for past 3 months (rationale: blood pressure below 100/60 mmHg may elevate the normally small risk of hypotension with nitrate supplementation) * Not taking medications that will interfere with administered medications (e.g., sildenafil interacts with nitroglycerin) * Body mass index (BMI) \<40 kg/m2 (vascular function measurements can be inaccurate in severely obese patients) Exclusion Criteria: * Life expectancy \<1 year * Uncontrolled hypertension, defined as blood pressure \> 160/100 mmHg in the past 3 months * History of severe liver disease * History of severe congestive heart failure (i.e., ejection fraction \< 35%) * History of hospitalizations within the last 3 months * Active infection or antibiotic therapy * Warfarin use * Vasculitis requiring immunosuppressive therapy within the last year * High dietary nitrate intake or current nitrate/nitrite supplementation; hypersensitivity to nitrates or nitrites * Glucose-6-phosphate dehydrogenase deficiency or blood methemoglobin \>2% * Unwilling to abstain from use of mouthwash or other oral hygiene practices (e.g., tongue scraping) outside of teeth brushing that disrupt the oral microbiome and would interfere with nitrate conversion to nitrite * Blood donation within 8 weeks prior to enrolling in the study; unwilling to abstain from donating blood for 8 weeks after completing the study