Sodium Bicarbonate Supplementation and Urinary TGF-β1 in Nonacidotic Diabetic Kidney Disease: A Randomized,
Kalani L Raphael1,2, Tom Greene2, Guo Wei2
1Medicine Section, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah; and.
Insights
Sodium bicarbonate did not significantly impact kidney injury markers in patients with diabetic kidney disease. This study found no reduction in urinary transforming growth factor-beta 1 (TGF-β1) or other markers over six months.
Area of Science:
- Nephrology
- Endocrinology
- Clinical Trials
Background:
- Previous studies showed sodium bicarbonate reduced urinary TGF-β1 in hypertensive CKD.
- The effect of sodium bicarbonate on kidney fibrosis and injury in diabetic kidney disease (DKD) with normal serum total CO2 is unknown.
Purpose of the Study:
- To investigate the efficacy of sodium bicarbonate in reducing kidney injury and fibrosis markers in patients with DKD.
- To assess the impact of sodium bicarbonate on urinary TGF-β1, KIM-1, fibronectin, NGAL, and UACR.
Main Methods:
- A 6-month randomized, double-blind, placebo-controlled trial involving 74 US veterans with DKD.
- Participants received oral sodium bicarbonate or placebo, with primary outcome being change in urinary TGF-β1/creatinine.
Main Results:
- Sodium bicarbonate increased serum total CO2 and urinary pH, and decreased urinary acid excretion.
- No significant changes were observed in urinary TGF-β1/creatinine, KIM-1/creatinine, fibronectin/creatinine, NGAL/creatinine, or UACR.
Conclusions:
- Sodium bicarbonate did not significantly reduce markers of kidney injury or fibrosis in patients with nonacidotic DKD over 6 months.
- Further research is needed to explore potential benefits in different patient populations or with longer treatment durations.
Background And Objectives:
In early-phase studies of individuals with hypertensive CKD and normal serum total CO2, sodium bicarbonate reduced urinary TGF-β1 levels and preserved kidney function. The effect of sodium bicarbonate on kidney fibrosis and injury markers in individuals with diabetic kidney disease and normal serum total CO2 is unknown.
Design, Setting, Participants, & Measurements:
We conducted a randomized, double-blinded, placebo-controlled study in 74 United States veterans with type 1 or 2 diabetes mellitus, eGFR of 15-89 ml/min per 1.73 m2, urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g, and serum total CO2 of 22-28 meq/L. Participants received oral sodium bicarbonate (0.5 meq/kg lean body wt per day; n=35) or placebo (n=39) for 6 months. The primary outcome was change in urinary TGF-β1-to-creatinine from baseline to months 3 and 6. Secondary outcomes included changes in urinary kidney injury molecule-1 (KIM-1)-to-creatinine, fibronectin-to-creatinine, neutrophil gelatinase-associated lipocalin (NGAL)-to-creatinine, and UACR from baseline to months 3 and 6.
Results:
Key baseline characteristics were age 72±8 years, eGFR of 51±18 ml/min per 1.73 m2, and serum total CO2 of 24±2 meq/L. Sodium bicarbonate treatment increased mean total CO2 by 1.2 (95% confidence interval [95% CI], 0.3 to 2.1) meq/L, increased urinary pH by 0.6 (95% CI, 0.5 to 0.8), and decreased urinary ammonium excretion by 5 (95% CI, 0 to 11) meq/d and urinary titratable acid excretion by 11 (95% CI, 5 to 18) meq/d. Sodium bicarbonate did not significantly change urinary TGF-β1/creatinine (difference in change, 13%, 95% CI, -10% to 40%; change within the sodium bicarbonate group, 8%, 95% CI, -10% to 28%; change within the placebo group, -4%, 95% CI, -19% to 13%). Similarly, no significant effect on KIM-1-to-creatinine (difference in change, -10%, 95% CI, -38% to 31%), fibronectin-to-creatinine (8%, 95% CI, -15% to 37%), NGAL-to-creatinine (-33%, 95% CI, -56% to 4%), or UACR (1%, 95% CI, -25% to 36%) was observed.
Conclusions:
In nonacidotic diabetic kidney disease, sodium bicarbonate did not significantly reduce urinary TGF-β1, KIM-1, fibronectin, NGAL, or UACR over 6 months.
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