The BASE Study: Bicarbonate Administration to Stabilize Estimated Glomerular Filtration Rate (eGFR)

Inclusion Criteria:

1. Serum bicarbonate 20-28 mEq/L at screening (the average of the two most recent values
in Baseline must be 20-28 mEq/L prior to randomization)

2. Moderate to severe chronic kidney disease (CKD) at the time of screening, defined as
one of the following:

- eGFR 20-44 ml/min/1.73m2 or

- eGFR 45-59 ml/min/1.73m2 plus random urinary albumin:creatinine (ACR) ≥100 mg/gm

3. Blood pressure <160/100 mm Hg at screening (must be <150/100 mm Hg prior to
randomization)

4. Lean body weight 38.0-96.0 kg at the time of screening

5. Age allowing legal consent without parental involvement (18-21 years, depending on
individual state regulations)

6. Able to provide consent

7. Able to travel to study visits

8. Able to read English

9. In the opinion of the site investigator, willing and able to follow the study
treatment regimen and comply with the site investigator's recommendations

10. In the opinion of the site investigator, medically stable

Exclusion Criteria:

1. Use of chronic daily oral alkali (such as sodium bicarbonate, sodium citrate,
potassium citrate, etc) with one exception: calcium carbonate ≤1500 mg/day is
allowed, as some will take this for the indication of bone health

2. On five or more antihypertensive and/or diuretic agents, regardless of the indication

3. Serum potassium <3.3 or ≥5.5 mEq/L at screening (must be 3.5-5.5 mEq/L prior to
randomization)

4. Self-reported vegetarian

5. New York Heart Association Class 3 or 4 heart failure symptoms, known left
ventricular ejection fraction ≤30%, or hospital admission for heart failure within
the past 3 months

6. Frequent urinary tract infections (≥2 in the past year)

7. Presence of indwelling urinary catheter or urinary conduit (such as neobladder or
urostomy)

8. Factors judged to limit adherence to interventions (e.g., alcoholism, history of
missing clinic visits, chronic gastrointestinal disorder that makes compliance with
the intervention unreliable)

9. Organ transplant recipients (excluding cornea)

10. Active glomerular disease requiring or potentially requiring immunosuppressive
treatment

11. Chronic immunosuppressive therapy (for ≥3 months) for any indication. This does not
include oral steroids <10 mg per day, inhaled steroids, or topical steroids

12. Anticipated initiation of dialysis or kidney transplantation within 12 months as
assessed by the site investigator

13. Current participation in another interventional research study

14. Malignancy requiring therapy within 2 years (basal or squamous cell skin carcinoma
and localized prostate cancer are exempted)

15. Pregnancy or planning to become pregnant or currently breast-feeding. Women of
childbearing potential (pre-menopausal and not surgically sterilized) will have urine
pregnancy test before enrollment.

16. Life expectancy <12 months as determined by the site investigator

17. Institutionalized individuals, including prisoners and nursing home residents

18. Plans to leave the immediate area within the next 12 months

19. Routinely leaves town for multiple weeks each year such that protocol visits would be
missed

20. Chronic use of supplemental oxygen

21. Use of both angiotensin-converting-enzyme inhibitor (ACEI) and Angiotensin II
Receptor Blockers (ARBs)