Background and objectives Metabolic acidosis contributes to muscle breakdown in patients with CKD, but whether its treatment improves functional outcomes is unknown. The choice of dose and tolerability of high doses remain unclear. In CKD patients with mild acidosis, this study evaluated the dose–response relationship of alkali with serum bicarbonate, its side effect profile, and its effect on muscle strength. Design, setting, participants, & measurements In this single-blinded pilot study from March of 2009 to August of 2010, 20 adults with estimated GFR 15–45 ml/min per 1.73 m2 and serum bicarbonate 20–24 mEq/L were treated during successive 2-week periods with placebo followed by escalating oral NaHCO3doses (0.3, 0.6, and 1.0 mEq/kg per day). At each visit, handgrip strength and time required to complete 5 and 10 repetitions of a sit-to-stand test were measured. Results Each 0.1 mEq/kg per day increase in dose produced a 0.33 mEq/L (95% confidence interval=0.23–0.43 mEq/L) higher serum bicarbonate. Sit-to-stand time improved after 6 weeks of oral NaHCO3 (23.8±1.4 versus 22.2±1.6 seconds for 10 repetitions, P=0.002), and urinary nitrogen excretion decreased (−0.70 g/g creatinine [95% confidence interval=−1.11 to −0.30] per 0.1 mEq/kg per day higher dose). No statistically significant change was seen in handgrip strength (29.5±9.6 versus 28.4±9.4 kg, P=0.12). Higher NaHCO3 doses were not associated with increased BP or greater edema. Conclusions NaHCO3 supplementation produces a dose-dependent increase in serum bicarbonate and improves lower extremity muscle strength after a short-term intervention in CKD patients with mild acidosis. Long-term studies are needed to determine if this finding translates into improved functional status.