Kidney Week

Abstract: SA-PO496

Among Patients Meeting the KDIGO CKD Practice Point Criterion for Treatment of Metabolic Acidosis, Higher Serum Bicarbonate Concentrations Are Associated with Slower CKD Progression

Session Information

• Acid-Base, Calcium, Potassium, and Magnesium Disorders: Clinical
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

• Singh, Bhupinder, Renibus Therapeutics, Southlake, Texas, United States

Bhupinder Singh, MD, FASN

• Tangri, Navdeep, University of Manitoba, Winnipeg, Manitoba, Canada

Navdeep Tangri, MD, PhD

• Chertow, Glenn M., Stanford University, Palo Alto, California, United States

Glenn M. Chertow, MD, MPH, FASN

• Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States

Pablo E. Pergola, MD, PhD

• Turner, Stewart A., Renibus Therapeutics, Southlake, Texas, United States

Stewart A. Turner, PhD

• Kendrick, Jessica B., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Jessica B. Kendrick, MD, MPH

• Wesson, Donald E., University of Texas, Austin, Texas, United States

Donald E. Wesson, MD, MBA, FASN

Background

Lower serum bicarbonate concentrations in patients with CKD and metabolic acidosis are associated with worse clinical outcomes including faster CKD progression. Less clear is to what extent raising bicarbonate delays CKD progression. The 2024 KDIGO CKD guideline recommends, as a practice point, the use of pharmacological treatment in patients with serum bicarbonate < 18 mEq/L. We explored the relation between achieved serum bicarbonate and CKD progression using data from the VALOR-CKD study, which evaluated the safety and efficacy of veverimer, a non-absorbed polymer that removes hydrochloric acid from the gastrointestinal tract.
In this study, 1,480 patients with CKD (eGFR 20-40 mL/min/1.73 m²) and metabolic acidosis (serum bicarbonate 12-20 mEq/L) were randomized, after a single-blind active treatment period, to veverimer or placebo and followed for a median of 24.5 months. The difference in achieved serum bicarbonate concentrations between treatment groups was only 1.3 mEq/L and the trial failed to show a slowing of CKD progression.

Methods

In a post-hoc analysis restricted to patients with baseline serum bicarbonate < 18 mEq/L, we evaluated the relation between the average serum bicarbonate concentration achieved over the course of the randomized treatment period (<20, ≥22 mEq/L, ie > 4 mEq/L serum bicarbonate increase), and CKD progression using a Cox proportional hazards model. CKD progression was defined as the time to the first kidney composite endpoint (KCE) of a confirmed reduction in eGFR ≥40%, ESKD (requiring dialysis or transplantation), or death.

Results

The patients who achieved average serum bicarbonate concentrations ≥22 mEq/L, irrespective of treatment received, experienced a significantly reduced risk of KCE, HR=0.52 (CI 0.36 to 0.75), p <0.0005, relative to those with serum bicarbonate concentrations <20 mEq/L.

Conclusion

This post-hoc analysis from the VALOR-CKD trial provides supportive evidence that in a CKD population with serum bicarbonate concentrations meeting the KDIGO practice point criterion for treatment of metabolic acidosis (< 18 mEq/L), higher achieved serum bicarbonate concentrations are associated with slower CKD progression.