Oral sodium bicarbonate supplementation may preserve kidney function in patients with CKD. However, the best dose to use in phase-3 trials testing this hypothesis is uncertain. The authors conducted a multicenter pilot study to assess the safety, tolerability, adherence, and pharmacodynamics of two doses of sodium bicarbonate, 0.8 and 0.5 meq/kg of lean body wt per day, over 28 weeks. They showed that the higher dose of sodium bicarbonate was well tolerated, reduced urinary ammonium excretion, and raised serum bicarbonate more than the lower dose, but it modestly increased urinary albumin excretion. These findings contribute to understanding the pharmacodynamic effects and patient acceptance of sodium bicarbonate in CKD.