Kidney Week Educational Symposia-Moving the Needle: Updated Evidence on Metabolic Acidosis

Video Transcription

Video Summary

This symposium reviews evolving evidence on metabolic acidosis in chronic kidney disease (CKD), emphasizing that acid retention can occur even with “normal” serum bicarbonate and may worsen outcomes. Current guidelines treat when bicarbonate falls below ~22 mmol/L, aiming to protect bone, muscle, CKD progression, and mortality, but “eubicarbonatemic” acidosis remains a key open question.<br /><br />Dr. Jessica Kendrick summarizes observational and mechanistic links between lower bicarbonate (and higher anion gap/acid retention) and cardiovascular risk: hypertension, endothelial dysfunction, cardiovascular events, mortality, and possibly cognitive impairment. Proposed pathways include increased ammoniagenesis with complement activation, RAAS and endothelin activation, inflammation, and bone turnover contributing to vascular calcification. Small crossover trials suggest sodium bicarbonate can improve flow-mediated dilation; a large open-label study showed better survival and fewer hospitalizations. Veverimer (an HCl-binding polymer) raises bicarbonate and improved a composite outcome, though cardiovascular endpoints remain uncertain. Optimal bicarbonate targets are unclear due to possible harms at higher levels (e.g., heart failure signals).<br /><br />Dr. Kalani Rafael reviews bicarbonate supplementation trials: several suggest slower CKD progression and possible survival benefit, potentially even in low-normal bicarbonate. Benefits for muscle/bone are inconsistent. Risks include sodium-related edema/hypertension (generally manageable), possible vascular calcification (animal concern, human unclear), mild hypokalemia, stone risk (possibly offset by higher citrate), and rare metabolic alkalosis.

Asset Subtitle

Snezana Petrovic, Jessica Kendrick, Kalani Raphael
Support is provided by an educational grant from Tricida, Inc.

Keywords

chronic kidney disease

metabolic acidosis

eubicarbonatemic acidosis

serum bicarbonate threshold 22 mmol/L

sodium bicarbonate supplementation

cardiovascular risk and endothelial dysfunction

anion gap and acid retention

veverimer HCl-binding polymer

CKD progression and mortality