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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

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
  • Isakova, Tamara, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
  • Ix, Joachim H., UCSD, San Diego, California, United States
  • Raj, Dominic S., GWU Medical Faculty Associates, Washington, District of Columbia, United States
  • Wolf, Myles, Duke University, Durham, North Carolina, United States
  • Fried, Linda F., VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States
  • Gassman, Jennifer J., Cleveland Clinic, Cleveland, Ohio, United States
  • Larive, Brett, Cleveland Clinic, Cleveland, Ohio, United States
  • Abbott, Kevin C., The National Institutes of Health, NIDDK, Bethesda, Maryland, United States
  • Mendley, Susan R., The National Institutes of Health, NIDDK, Bethesda, Maryland, United States
  • Block, Geoffrey A., Colorado Kidney Care, Denver, Colorado, United States
  • Li, Ping, GWU Medical Faculty Associates, Washington, District of Columbia, United States
  • Middleton, John Paul, Duke University, Durham, North Carolina, United States
  • Sprague, Stuart M., NorthShore University HealthSystem University of Chicago Pritzker School of Medicine, Chicago, Illinois, United States
  • Wesson, Donald E., Baylor Scott and White Health and Wellness Center, Dallas, Texas, United States
  • Cheung, Alfred K., University of Utah, Salt Lake City, Utah, United States

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
Acid-Base IndicatorHigher-Dose NaHCO3 vs. Plac at week 28Lower-Dose NaHCO3 vs. Plac at week 28
Estimate95% CIEstimate95% CI
S-HCO3- (meq/L)1.40.6 to 2.20.1-0.8 to 1.1
24-hr U-NH4+, % difference-48-57 to -36-33-47 to -16
24-hr U-pH0.80.6 to 1.00.60.3 to 0.8

Funding

  • NIDDK Support