Kidney Week

Abstract: SA-OR036

A Multicenter, Randomized Pilot Study of Oral Sodium Bicarbonate Supplementation in Non- to Mildly-Acidotic CKD: The BASE Pilot Study

Session Information

• Fluids and Electrolytes: Clinical, Translational, and Acid-Base
  October 27, 2018 | Location: 23A, San Diego Convention Center
  Abstract Time: 05:30 PM - 05:42 PM

Category: Fluid and Electrolytes

• 902 Fluid and Electrolytes: Clinical

Authors

• Raphael, Kalani L., VA Salt Lake City Health Care System, Salt Lake City, Utah, United States

Kalani L. Raphael, MD, MS, FASN



Dr. Kalani Raphael is a clinical nephrologist and Associate Professor in the Division of Nephrology and Hypertension at University of Utah Health and VA Salt Lake City Health Care System. His primary research interest is in metabolic acidosis in chronic kidney disease patients.

• Isakova, Tamara, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States

Tamara Isakova,

• Ix, Joachim H., UCSD, San Diego, California, United States

Joachim H. Ix,

• Raj, Dominic S., GWU Medical Faculty Associates, Washington, District of Columbia, United States

Dominic S. Raj,

• Wolf, Myles, Duke University, Durham, North Carolina, United States

Myles Wolf,

• Fried, Linda F., VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States

Linda F. Fried,

• Gassman, Jennifer J., Cleveland Clinic, Cleveland, Ohio, United States

Jennifer J. Gassman,

• Larive, Brett, Cleveland Clinic, Cleveland, Ohio, United States

Brett Larive,

• Abbott, Kevin C., The National Institutes of Health, NIDDK, Bethesda, Maryland, United States

Kevin C. Abbott,

• Mendley, Susan R., The National Institutes of Health, NIDDK, Bethesda, Maryland, United States

Susan R. Mendley,

• Block, Geoffrey A., Colorado Kidney Care, Denver, Colorado, United States

Geoffrey A. Block,

• Li, Ping, GWU Medical Faculty Associates, Washington, District of Columbia, United States

Ping Li,

• Middleton, John Paul, Duke University, Durham, North Carolina, United States

John Paul Middleton,

• Sprague, Stuart M., NorthShore University HealthSystem University of Chicago Pritzker School of Medicine, Chicago, Illinois, United States

Stuart M. Sprague,

• Wesson, Donald E., Baylor Scott and White Health and Wellness Center, Dallas, Texas, United States

Donald E. Wesson,

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

Alfred K. Cheung,

Group or Team Name

• The CKD Pilot Studies Consortium

Background

Chronic oral NaHCO₃ may preserve GFR in CKD, even in those with normal serum (S) HCO₃^-. However, definitive proof of efficacy and the optimal dose have not been demonstrated. We performed a randomized, double-blinded, placebo-controlled multicenter pilot study to determine the safety, tolerability, compliance, and pharmacodynamics of two doses of oral NaHCO₃ and the feasibility to conduct a multicenter Phase-3 trial.

Methods

Individuals (n=194) with mean age 68 yrs, eGFR 37 ml/min/1.73m², ACR 530 mg/g, and S-HCO₃^- 24 meq/L (range 20-28 meq/L) were randomized to higher-dose (HD) (0.8 meq/kg-LBW/d; n=90) or lower-dose (LD) (0.5 meq/kg-LBW/d; n=52) NaHCO₃ or placebo (Plac; n=52) for 28 weeks. The dose was adjusted depending on clinical and laboratory side-effects. The prescribed dose at study completion was the primary outcome. Feasibility for a Phase 3 trial was defined a priori as ≥67% of participants completing the study on full dose and ≥80% on ≥25% of the dose. Pharmacodynamics were assessed by S-HCO₃^-, 24-hour urine NH₄⁺ (U-NH₄⁺) and pH (U-pH).

Results

87% in HD, 98% in LD, and 88% in Plac completed the study on full dose, while 91% in HD, 98% in LD, and 94% in Plac completed the study on ≥25% of the dose. Compliance by pill count was ≥88%, with >80% of participants having ≥80% compliance in all arms during follow-up. BP, weight, and S-K⁺ were similar between Plac, LD and HD during follow-up. Table 1 shows dose-response effects of NaHCO₃ on S-HCO₃^-, U-pH and U-NH₄⁺.

Conclusion

In persons with non- to mildly-acidotic stage 3/4 CKD, safety, tolerability and compliance of HD and LD NaHCO3 were each comparable to Plac. NaHCO₃ had a mild effect on S-HCO₃^- and substantial dose-dependent effects on U-NH₄⁺ and U-pH, but no significant effect on BP, weight, or S-K⁺. A Phase-3 multicenter trial using NaHCO₃ 0.8 meq/kg-LBW/d is feasible.

Dose response effects of NaHCO3 on acid-base indices

Funding

• NIDDK Support