Sodium Bicarbonate Treatment and Vascular Function in CKD: A Randomized, Double-Blind, Placebo-Controlled Trial

Authors

Jessica Kendrick, Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
Zhiying You, Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
Emily Andrews, Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
Heather Farmer-Bailey, Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
Kerrie Moreau, Division of Geriatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado
Michel Chonchol, Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
Cortney Steele, Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
Wei Wang, Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
Kristen L. Nowak, Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
Nayana Patel, Division of Radiology, University of New Mexico Health Sciences Center, Albuquerque, New MexicoFollow

Document Type

Article

Publication Date

8-1-2023

Abstract

SIGNIFICANCE STATEMENT: Lower serum bicarbonate levels, even within the normal range, are strongly linked to risks of cardiovascular disease in CKD, possibly by modifying vascular function. In this randomized, controlled trial, treatment with sodium bicarbonate (NaHCO 3 ) did not improve vascular endothelial function or reduce arterial stiffness in participants with CKD stage 3b-4 with normal serum bicarbonate levels. In addition, NaHCO 3 treatment did not reduce left ventricular mass index. NaHCO 3 did increase plasma bicarbonate levels and urinary citrate excretion and reduce urinary ammonium excretion, indicating that the intervention was indeed effective. NaHCO 3 therapy was safe with no significant changes in BP, weight, or edema. These results do not support the use of NaHCO 3 for vascular dysfunction in participants with CKD.

BACKGROUND: Lower serum bicarbonate levels, even within the normal range, are strongly linked to risks of cardiovascular disease in CKD, possibly by modifying vascular function. Prospective interventional trials with sodium bicarbonate (NaHCO 3 ) are lacking.

METHODS: We conducted a randomized, double-blind, placebo-controlled trial examining the effect of NaHCO 3 on vascular function in 109 patients with CKD stage 3b-4 (eGFR 15-44 ml/min per 1.73 m 2 ) with normal serum bicarbonate levels (22-27 mEq/L). Participants were randomized 1:1 to NaHCO 3 or placebo at a dose of 0.5 mEq/lean body weight-kg per day for 12 months. The coprimary end points were change in brachial artery flow-mediated dilation (FMD) and change in aortic pulse wave velocity over 12 months.

RESULTS: Ninety patients completed this study. After 12 months, plasma bicarbonate levels increased significantly in the NaHCO 3 group compared with placebo (mean [SD] difference between groups 1.35±2.1, P = 0.003). NaHCO 3 treatment did not result in a significant improvement in aortic pulse wave velocity from baseline. NaHCO 3 did result in a significant increase in flow-mediated dilation after 1 month; however, this effect disappeared at 6 and 12 months. NaHCO 3 resulted in a significant increase in 24-hour urine citrate and pH and a significant decrease in 24-hour urine ammonia. There was no significant change in left ventricular mass index, ejection fraction, or eGFR with NaHCO 3 . NaHCO 3 treatment was safe and well-tolerated with no significant changes in BP, antihypertensive medication, weight, plasma calcium, or potassium levels.

CONCLUSION: Our results do not support the use of NaHCO 3 for vascular dysfunction in participants with CKD and normal serum bicarbonate levels.

Publisher

American Society of Nephrology

Publication Title

Journal of the American Society of Nephrology : JASN

ISSN

1533-3450

Volume

34

Issue

8

First Page

1433

Last Page

1444

DOI

10.1681/ASN.0000000000000161

Recommended Citation

Kendrick J, You Z, Andrews E, Farmer-Bailey H, Moreau K, Chonchol M, Steele C, Wang W, Nowak KL, Patel N. Sodium Bicarbonate Treatment and Vascular Function in CKD: A Randomized, Double-Blind, Placebo-Controlled Trial. J Am Soc Nephrol. 2023 Aug 1;34(8):1433-1444. doi: 10.1681/ASN.0000000000000161. Epub 2023 May 25. PMID: 37228030.