Higher Serum Bicarbonate Concentrations, Slower CKD Progression With Metabolic Acidosis

Oral alkali therapy can raise serum bicarbonate concentrations and has been associated with slowing chronic kidney disease (CKD) progression. Researchers led by Bhupinder Singh performed a post hoc analysis from the phase 3 VALOR-CKD trial to study the relationship between serum bicarbonate concentrations and CKD progression. They reported results at the National Kidney Foundation Spring Clinical Meetings.

VALOR-CKD was conducted to assess the safety and efficacy of veverimer, a nonabsorbed polymer that removes hydrochloric acid from the gastrointestinal tract. The randomized, double-blind, placebo-controlled trial included 1480 patients who had CKD (estimated glomerular filtration rate [eGFR], 20-40 mL/min/1.73 m²) and metabolic acidosis (serum bicarbonate, 12-20 mEq/L). Following single-blind active treatment for up to 8.0 weeks, randomized patient groups received either veverimer or placebo and were followed for a median of 24.5 months.

VALOR-CKD did not find a slowdown of CKD progression (defined as time to first kidney composite end point [KCE] of a confirmed reduction in eGFR ≥40%, end-stage kidney disease requiring dialysis or transplantation, or death due to kidney disease).

In their post hoc analysis, Singh’s team used a Cox proportional hazards model to assess the relationships among three levels of average serum bicarbonate concentrations reached throughout the randomized treatment period (<20, 20 to <22, and ≥22 mEq/L) and the KCE. They found that patients with average serum bicarbonate concentrations 20 to <22 and ≥22 mEq/L had a reduced risk of KCE—hazard ratio (HR), 0.67 (95% CI, 0.49-0.90); P<.0078 and HR, 0.50 (95% CI, 0.37-0.67); P<.0001, respectively—versus those with concentrations <20 mEq/L. This was true regardless of whether patients were receiving veverimer or placebo.

The researchers asserted that their results support that higher serum bicarbonate concentrations in patients with CKD and metabolic acidosis are associated with slower CKD progression.

Source: Singh B, Tangri N, Bushinsky D, et al. Serum bicarbonate concentrations and CKD progression in patients with metabolic acidosis: evidence from VALOR-CKD. Presented at the National Kidney Foundation Spring Clinical Meetings 2024; May 14-18, 2024; Long Beach, California.