BMC Nephrology · Aug 12, 2025

Effects of sodium bicarbonate therapy on cognitive and cerebrovascular function in midlife and older adults with chronic kidney disease: a pilot randomized trial

By Gu F, You Z, Hawkins N et al.

INTRODUCTION: Metabolic acidosis may create a pathway to cognitive impairment in chronic kidney disease (CKD) by contributing to cerebrovascular dysfunction. Trials examining the effect of sodium bicarbonate (NaHCO₃) on cognitive function are lacking. METHODS: We conducted a randomized, double-blind, placebo-controlled pilot study examining the effect of 12 months of NaHCO₃ on cognitive function in 34 patients aged 50-80 years with CKD stage 3b-4 (eGFR 15-44 ml/min/1.73m²) with metabolic acidosis (serum bicarbonate level 16-22 mEq/L). Participants were randomized 1:1 to NaHCO₃ or placebo. The primary endpoint was change in overall cognition (Cognitive Function Composite score) assessed by the NIH Toolbox® Cognition Battery over 12 months. Secondary endpoints were change in cerebrovascular reactivity and pulsatility of the middle cerebral artery (MCA) assessed by Transcranial Doppler Ultrasonography over 12 months. RESULTS: 33 patients completed the study. After 12 months of treatment with NaHCO₃ therapy, the Cognitive Function Composite score increased significantly from baseline (mean ± SD, 47.3 ± 8.5 to 49.3 ± 11.0, p = 0.03), however, there was no difference compared to placebo (p = 0.39). NaHCO₃ therapy resulted in a significant reduction in time to perform the Trail Making Test-A (median [IQR], 31.3 [27.0, 36.3] to 29.0 [19.4, 38.2] seconds, p = 0.02), however there was no difference compared to placebo (p = 0.29). After 12 months of treatment, there was a significant increase in resting pulsatility index of the MCA in the placebo group, but there were no statistical differences between groups (p = 0.71). NaHCO₃ treatment resulted in a significant decrease in baseline mean blood flow velocity of the MCA (p = 0.03), but there was no difference from placebo (p = 0.11). CONCLUSIONS: Although there were trends supporting a role for sodium bicarbonate in having an effect on cognitive function, this was not significant in this underpowered study. A larger study is recommended. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04600323) on 10/19/2020.

doi.org/10.1186/s12882-025-04388-6 Open access PubMed 40797182 Interventions