Sodium bicarbonate supplementation and urinary TGF-β1 in nonacidotic diabetic kidney disease a randomized, controlled trial

Background and objectives In early-phase studies of individuals with hypertensive CKD and normal serum total CO₂, sodium bicarbonate reduced urinary TGF-b1 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; n535) or placebo (n539) for 6 months. The primary outcome was change in urinary TGF-b1-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 7268 years, eGFR of 51618 ml/min per 1.73 m², and serumtotal CO₂ of 2462 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 excretionby 11 (95% CI, 5 to 18) meq/d. Sodiumbicarbonate did not significantly change urinary TGF-b1/creatinine (difference in change, 13%, 95% CI, 210% to 40%; change within the sodium bicarbonate group, 8%, 95% CI, 210% to 28%; change within the placebo group, 24%, 95% CI, 219% to 13%). Similarly, no significant effect on KIM-1-to-creatinine (difference in change, 210%, 95% CI, 238% to 31%), fibronectin-to-creatinine (8%, 95% CI, 215% to 37%), NGAL-to-creatinine (233%, 95% CI, 256% to 4%), or UACR (1%, 95% CI, 225% to 36%) was observed. Conclusions In nonacidotic diabetic kidney disease, sodium bicarbonate did not significantly reduce urinary TGF-b1, KIM-1, fibronectin, NGAL, or UACR over 6 months.