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Sodium Bicarbonate Supplementation and Urinary TGF-?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-?1 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-?1-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-?1/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-?1, KIM-1, fibronectin, NGAL, or UACR over 6 months.

SUBMITTER: Raphael KL

PROVIDER: S-EPMC7015087 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Raphael Kalani L KL Greene Tom T Wei Guo G Bullshoe Tristin T Tuttle Kunani K Cheung Alfred K AK Beddhu Srinivasan S

Clinical journal of the American Society of Nephrology : CJASN 20200123 2

<h4>Background and objectives</h4>In early-phase studies of individuals with hypertensive CKD and normal serum total CO<sub>2</sub>, sodium bicarbonate reduced urinary TGF-<i>β</i>1 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 CO<sub>2</sub> is unknown.<h4>Design, setting, participants, & measurements</h4>We conducted a randomized, double-blinded, placebo-controlled ...[more]

PMID: 31974286

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