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

Kalani L. Raphael, Tom Greene, Guo Wei, Tristin Bullshoe, Kunani Tuttle, Alfred K. Cheung, Srinivasan Beddhu

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)200-208
Number of pages9
JournalClinical Journal of the American Society of Nephrology
Issue number2
StatePublished - Feb 7 2020

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation


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