TY - JOUR
T1 - Sodium bicarbonate supplementation and urinary TGF-β1 in nonacidotic diabetic kidney disease a randomized, controlled trial
AU - Raphael, Kalani L.
AU - Greene, Tom
AU - Wei, Guo
AU - Bullshoe, Tristin
AU - Tuttle, Kunani
AU - Cheung, Alfred K.
AU - Beddhu, Srinivasan
N1 - Funding Information:
Dr. Beddhu is supported by grants from Bayer, Boehringer In-gelheim, and the National Institutes of Health, outside of the submitted work. Dr. Beddhu also reports receiving consultant fees from Reata Pharmaceuticals outside of the submitted work. Dr. Cheung is supported by grants from the National Institutes of Health. Dr. Greene is supported by a grant from the National Institutes of Health and reports receiving statistical consulting fees from DU-RECT Corporation, Janssen Pharmaceuticals, and Pfizer, Inc., outside of the submitted work. Dr. Raphael is supported by grants from the National Institutes of Health and US Department of Veterans Affairs Clinical Sciences Research and Development Service outside the submitted work. Dr. Raphael reports a one-time consulting fee from Tricida, Inc. in October 2016 outside the submitted work. Mr. Bullshoe, Ms. Tuttle, and Mr. Wei have nothing to disclose.
Funding Information:
This study was supported by the US Department of Veterans Affairs Clinical Sciences Research and Development Service Career Development Award (IK2 CX000537, to Dr. Raphael).
Funding Information:
This study was supported by the US Department of Veterans Affairs Clinical Sciences Research and Development Service Career Development Award (IK2 CX000537, to Dr. Raphael).. Dr. Beddhu, Dr. Cheung, Dr. Greene, and Dr. Raphael designed the study. Dr. Raphael enrolled participants. Mr. Bullshoe and Dr. Raphael performed laboratory measurements. Dr. Greene, Dr. Raphael, and Mr. Wei analyzed the data. Mr. Bullshoe, Dr. Raphael, and Ms. Tuttle prepared the figures and tables. Dr. Raphael drafted and revised the manuscript. All authors contributed significantly to the analysis and interpretation of the data, critically revised the manuscript, approved the final version of the manuscript, and agree to be accountable for all aspects of the work. The investigators wish to acknowledge the study participants and the following members of the research team: Jennifer Zitterkoph, Megan Varner, Katherine Mackin, and Sarah Neagle. The contents do not represent the views of the US Department of Veterans Affairs or the US Government.
Funding Information:
The study was funded by US Department of Veterans Affairs Clinical Sciences Research and Development Service and was approved by Institutional Review Boards of the University of Utah and VASLCHCS. All participants signed an informed consent document. The study was performed under the principles embodied in the Declaration of Helsinki. A Data Monitoring Committee, established by the Department of Veterans Affairs Clinical Sciences Research and Development Service, provided oversight of the study. The study was registered at Clinicaltrials.gov (identifier NCT01574157).
Publisher Copyright:
© 2020 by the American Society of Nephrology.
PY - 2020/2/7
Y1 - 2020/2/7
N2 - 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.
AB - 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.
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U2 - 10.2215/CJN.06600619
DO - 10.2215/CJN.06600619
M3 - Article
C2 - 31974286
AN - SCOPUS:85079103319
SN - 1555-9041
VL - 15
SP - 200
EP - 208
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 2
ER -