Kidney Week

Abstract: TH-PO1107

Effect of Sodium Bicarbonate on Plasma α-Klotho Levels in CKD

Session Information

• CKD: Therapies, Innovations, and Insights
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Price, Tara R, University of Utah Health, Salt Lake City, Utah, United States

Tara R Price, PhD

• Koike, Seiji, Oregon Health & Science University, Portland, Oregon, United States

Seiji Koike, MS

• Lapidus, Jodi A., Oregon Health & Science University, Portland, Oregon, United States

Jodi A. Lapidus, PhD

• Cheung, Alfred K., University of Utah Health, Salt Lake City, Utah, United States

Alfred K. Cheung, MD

• Chen, Wei, Albert Einstein College of Medicine, New York, New York, United States

Wei Chen, MD, MS, FASN

• Hostetter, Thomas H., The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States

Thomas H. Hostetter, MD

• Abramowitz, Matthew K., Albert Einstein College of Medicine, New York, New York, United States

Matthew K. Abramowitz, MD, MS, FASN

• Melamed, Michal L., NYU Langone Health, New York, New York, United States

Michal L. Melamed, MD

• Dobre, Mirela A., University Hospitals, Cleveland, Ohio, United States

Mirela A. Dobre, MD, MPH, FASN

• Ix, Joachim H., University of California San Diego Department of Medicine, La Jolla, California, United States

Joachim H. Ix, MD, FASN

• Raphael, Kalani L., University of Utah Health, Salt Lake City, Utah, United States

Kalani L. Raphael, MD, MS, FASN

Background

α-Klotho is an “anti-aging” protein highly expressed by the kidney. Circulating, soluble klotho (sKlotho) levels decline with aging and low levels are associated with poor outcomes. Prior studies suggest that urinary alkalinization with NaHCO₃ may increase sKlotho levels and provide a strategy to study the effects of manipulating sKlotho levels on aging.

Methods

We determined the effect of NaHCO₃ on sKlotho in post hoc analyses of two published NaHCO₃ trials in CKD: the VA-Bicarb Trial and Alkali Therapy in CKD Trial. Participants were randomized to receive 0.4-0.5 mEq/kg/d NaHCO₃ or placebo. sKlotho was measured by ELISA at baseline, month 3, and month 6. We compared sKlotho in active and control groups by fitting linear mixed-effects models to account for person-level variation in baseline concentrations using residual maximum likelihood.

Results

In VA Bicarb (n=74), mean age was 72±8 yrs, mean eGFR was 51±18 mL/min/1.73m², and mean sKlotho was 570±232 pg/mL. Mean sKlotho levels were 125 (95% CI, 10 to 239; p=0.03) and 107 (95% CI, -8 to 222; p=0.07) pg/mL higher at month 3 and 6, respectively, in NaHCO₃ treated vs. placebo. In Alkali Therapy in CKD (n=149), mean age was 61±13 yrs, mean eGFR was 36±11 ml/min/1.73m², and mean sKlotho was 573±304 pg/mL. Mean sKlotho levels were 50 (95% CI, -55 to 156; p=0.35) and 58 (95% CI, -29 to 164; p=0.29) pg/mL higher at month 3 and 6, respectively, in NaHCO₃ treated vs. placebo. Combining results from both studies, mean sKlotho levels were 74 (95% CI, -6 to 153; p=0.07) and 73 (95% CI, -7 to 154; p=0.07) pg/mL higher at month 3 and 6, respectively, in NaHCO₃ treated vs. placebo (Figure).

Conclusion

While not statistically significant with the available power, these results support the hypothesis that NaHCO₃ increases plasma sKlotho levels in persons with CKD. The numerically greater increase in sKlotho in VA Bicarb may indicate NaHCO₃ is more effective in those with greater nephron mass (i.e., higher eGFR).

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025fjz6pnyg