Sodium Bicarbonate Supplementation and Urinary TGF- β 1 in Nonacidotic Diabetic Kidney Disease: A Randomized, Controlled Trial

Abstract

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.

Keywords: TGF-beta; acidosis; albumins; ammonium compounds; bicarbonate; carbon dioxide; chronic kidney disease; chronic renal insufficiency; creatinine; diabetes mellitus; diabetic nephropathies; fibronectins; hepatitis A virus cellular receptor 1; human FN1 protein; human HAVCR1 protein; human LCN2 protein; humans; kidney function tests; lipocalin; sodium bicarbonate; transforming growth factors; veterans.