Pilot Study of Sodium Bicarbonate in Generally Healthy People With Low Bicarbonate

CKD affects 25 million Americans and the risks of cardiovascular morbidity, hospitalizations,
and death are substantially higher for people with CKD. Furthermore, 6% of the total Medicare
budget is spent on 600,000 people with end-stage renal disease. Thus, CKD is highly
prevalent, associates with poor outcomes, and is a tremendous financial burden to society.

Apart from treating hypertension and diabetes, there are no therapies that prevent CKD.
However, results from two studies have found that low serum bicarbonate levels increase risk
of developing CKD, which suggests that normalizing low serum bicarbonate may prevent CKD.

One way to raise low serum bicarbonate is by taking sodium bicarbonate. Whether sodium
bicarbonate, which is commonly prescribed to raise low serum bicarbonate in people with CKD,
can raise low bicarbonate in people without CKD is uncertain because the reason bicarbonate
is low in people without CKD is unclear. This is because low bicarbonate by itself cannot
distinguish whether the acid-base abnormality is primary metabolic acidosis or respiratory
alkalosis. The former process is readily corrected with alkali. However, the administration
of alkali in the latter situation may not raise bicarbonate concentration.

Therefore, the purpose of this pilot study is to determine whether oral sodium bicarbonate
can raise low serum bicarbonate in people without renal disease.

The study is a single-arm open label study of 15 individuals without CKD with low serum
bicarbonate concentration. The study duration is 10 weeks. After completing the baseline
visit, participants will take oral sodium bicarbonate (initial dose level: 0.3
milliequivalents per kilogram per day (mEq/kg/d) for 6 weeks (On-treatment period), followed
by a 4 week Off-treatment period. Serum concentrations of sodium bicarbonate will be tested
during the treatment period, at the end of the On-treatment period (Week 6) and at the end of
the Off-treatment period (Week 10).

Inclusion Criteria:

- Estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73m2

- Urinary albumin/creatinine ratio < 30 mg/gm

- Serum bicarbonate ≤ 23 mEq/L (average of the two most recent measurements within the
past year)

- Age ≥ 50 years

Exclusion Criteria:

- Blood pressure ≥ 160/100 mm Hg

- Serum potassium < 3.5 mEq/L

- New York Heart Association Class 3 or 4 heart failure symptoms

- Chronic oxygen therapy

- Chronic obstructive pulmonary disease requiring daily bronchodilator or prednisone
therapy

- Weight ≥ 160 kg

- Use of sodium bicarbonate, sodium citrate, potassium citrate, or potassium bicarbonate
within the previous two weeks.