Effects of sodium bicarbonate therapy on cognitive and cerebrovascular function in midlife and older adults with chronic kidney disease: a pilot randomized trial.
Fangning Gu, Zhiying You, Nell Hawkins, Rachael Reddin, Rahaf Hamour, Allison Shapiro, Christina Coughlan, Douglas Seals, Seth Furgeson, Angelina Dixon, Kristen L Nowak, Jessica Kendrick
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Abstract
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.
期刊介绍：
BMC Nephrology is an open access journal publishing original peer-reviewed research articles in all aspects of the prevention, diagnosis and management of kidney and associated disorders, as well as related molecular genetics, pathophysiology, and epidemiology.
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