Abstract: SA-PO153
Effect of Oral Sodium Bicarbonate on Urine TGF-β1 in Non-Acidotic Diabetic Kidney Disease (DKD)
Session Information
- Diabetic Kidney Disease: Clinical - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 602 Diabetic Kidney Disease: Clinical
Authors
- Raphael, Kalani L., VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
- Greene, Tom, University of Utah, Salt Lake City, Utah, United States
- Wei, Guo, University of Utah, Salt Lake City, Utah, United States
- Cheung, Alfred K., VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
- Beddhu, Srinivasan, VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
Background
Oral NaHCO3 may preserve GFR in CKD patients with normal serum (s) HCO3- by attenuating physiological responses that enhance H+ excretion to maintain normal s-HCO3-, but cause kidney fibrosis. Along these lines, urine (u) NH4+ is directly associated with uTGF-β1 in CKD. NaHCO3 reduces uNH4+ and, in hypertensive CKD, uTGF-β1. Whether NaHCO3 reduces uTGF-β1 in DKD is unknown.
Methods
We conducted a single-center, randomized, double-blinded, placebo-controlled study in 74 US veterans with stage 2-4 DKD, ACR ≥30 mg/g, and s-HCO3- 22-28 meq/L. Participants received NaHCO3 (0.5 meq/kg-LBW/d, n=35) or placebo (n=39) for 6 months. The primary analysis applied a mixed effect model to compare mean △ from baseline in uTGF-β1/Cr over 3- and 6-months after controlling for baseline uTGF-β1/Cr.
Results
Mean baseline values were age 71 years, eGFR 51 ml/min/1.73m2, SBP 127 mm Hg, ACR (median) 121 mg/g, s-HCO3- 24 meq/L, u-pH 5.5, uNH4+ 1.4 meq/hr, and u-titratable acids (uTA) 1.3 meq/hr. Baseline characteristics were similar between groups. NaHCO3 had expected effects on u-pH, u-TA, and s-HCO3- but did not lower uNH4+ (Table) or uTGF-β1/Cr (Figure). NaHCO3 had no effect on ACR, however eGFR was higher with NaHCO3 (5.7 ml/min/1.73m2, 95% CI 1.2-10.2). There were no significant differences in BP, weight, or s-K+ between groups during follow-up.
Conclusion
Oral NaHCO3 did not reduce uTGF-β1 or uNH4+ in persons with non-acidotic DKD. The effect of NaHCO3 on kidney NH3 production may be attenuated in DKD, perhaps because kidney gluconeogenesis also produces NH3. NaHCO3 increased eGFR, however long-term effects of NaHCO3 on eGFR in DKD should be determined.
Mean values of acid-base indices over 3- and 6-months by treatment group.
| Acid-base variable | Placebo | NaHCO3 | p |
| s-HCO3- (meq/L) | 24.3 (1.8) | 25.4 (2.6) | 0.07 |
| u-pH | 5.5 (0.4) | 6.2 (0.5) | <0.01 |
| u-TA (meq/hr) | 1.3 (0.7) | 0.9 (0.6) | 0.02 |
| u-NH4+ (meq/hr) | 1.3 (0.7) | 1.2 (0.7) | 0.47 |
Funding
- Veterans Affairs Support