Effect of Treatment of Metabolic Acidosis on Vascular Endothelial Function in Patients with CKD: A Pilot Randomized Cross-Over Study

Background and objectives

We examined the effect of alkali replacement for metabolic acidosis on vascular endothelial function in patients with CKD.

Methods

We performed a pilot, prospective, open-label 14-week crossover study examining the effect of oral sodium bicarbonate treatment on vascular function in 20 patients with an eGFR of 15–44 ml/min per 1.73 m² with low serum bicarbonate levels (16–21 mEq/L). Each period was 6 weeks in duration with a 2-week washout period in between. Patients were treated to goal serum bicarbonate of ≥23 mEq/L. The primary end point was change in brachial artery flow-mediated dilation (FMD) between treatment and control conditions. Secondary end points included changes in markers of inflammation, bone turnover, mineral metabolism, and calcification.

Results

Eighteen patients completed the study and were included in the primary efficacy analysis. The mean (SD) age and eGFR were 59 (12) years and 26 (8) ml/min per 1.73 m², respectively. Serum bicarbonate increased significantly with sodium bicarbonate treatment (+2.7±2.9 mEq/L, P≤0.001), whereas there was no change in bicarbonate levels in the control group. FMD significantly improved after sodium bicarbonate therapy (mean±SD, FMD baseline: 4.1%±4.1%; 6 weeks: 5.2%±2.9%; P=0.04) There was no significant change in FMD in the control group (mean±SD, FMD baseline: 4.6%±3.1%; 6 weeks: 4.1%±3.4%; P=0.20). Compared with control, sodium bicarbonate treatment resulted in a significant increase in FMD (mean, 1.8%; 95% confidence interval, 0.3 to 3.3; P=0.02). There was no significant change in bone markers or serum calcification propensity with treatment. Serum phosphorus and intact fibroblast growth factor 23 increased significantly during treatment.

Conclusions

Treatment of metabolic acidosis with sodium bicarbonate significantly improved vascular endothelial function in patients with stages 3b and 4 CKD.

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