TY - JOUR
T1 - Effect of Vitamin B12 Levels on the Association Between Folic Acid Treatment and CKD Progression
T2 - A Post Hoc Analysis of a Folic Acid Interventional Trial
AU - Li, Youbao
AU - Spence, J. David
AU - Wang, Xiaobin
AU - Huo, Yong
AU - Xu, Xiping
AU - Qin, Xianhui
N1 - Funding Information:
Youbao Li, MD, J. David Spence, MD, Xiaobin Wang, MD, ScD, Yong Huo, MD, Xiping Xu, MD, PhD, and Xianhui Qin, MD, PhD. Study concept and design: all authors; conduct of study: YL, XW, YH, XQ; data collection and analysis: YL, XQ. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. The study was supported by funding from the National Key Research and Development Program (2016YFE0205400, 2016YFC0903103, 2018ZX09739, 2018ZX09301034 003). The funding body had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr Spence is a consultant to Orphan Technologies, a company that makes a truncated human cystathionine beta synthase for treatment of classic homocystinuria. The remaining authors declare that they have no relevant financial interests. Received April 8, 2019. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form July 13, 2019.
Funding Information:
The study was supported by funding from the National Key Research and Development Program ( 2016YFE0205400 , 2016YFC0903103 , 2018ZX09739 , 2018ZX09301034 003 ). The funding body had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2019 National Kidney Foundation, Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3
Y1 - 2020/3
N2 - Rationale & Objective: In populations with folic acid fortification or supplementation, the main nutritional determinant of total homocysteine levels is vitamin B12 (B12) status. We aimed to evaluate the modifying effect of B12 levels on the association between folic acid treatment and chronic kidney disease (CKD) progression. Study Design: A post hoc analysis of an interventional trial. Setting & Participants: This is a post hoc analysis of 1,374 hypertensive adults with mild to moderate CKD and B12 measurements at baseline from the kidney disease substudy of the China Stroke Primary Prevention Trial (CSPPT), conducted in 20 communities in Jiangsu province in China, a region with low folate consumption. Interventions: Assignments to a double-blinded daily treatment of enalapril, 10 mg, and folic acid, 0.8 mg; or enalapril, 10 mg, alone. Outcomes: The primary outcome was progression of CKD (defined as a decrease in estimated glomerular filtration rate [eGFR] ≥ 30% and to a level of <60 mL/min/1.73 m2 if baseline eGFR was ≥60 mL/min/1.73 m2; or a decrease in eGFR ≥ 50% if baseline eGFR was <60 mL/min/1.73 m2; or kidney failure). Results: Mean baseline eGFR in this study was 86.1 ± 20.5 (SD) mL/min/1.73 m2. Median treatment duration was 4.4 years. Among participants with higher baseline B12 levels (≥248 pmol/L), compared to enalapril alone, enalapril–folic acid treatment was associated with an 83% reduction in the odds of the primary outcome (OR, 0.17; 95% CI, 0.07-0.40). However, among those with baseline B12 levels < 248 pmol/L (metabolic B12 deficiency), there was no significant group difference in the primary outcome (OR, 1.21; 95% CI, 0.51-2.85). The interaction between B12 level and folic acid treatment was significant (P = 0.001). Limitations: The analysis is post hoc and event rate is low. Conclusions: Folic acid treatment was associated with a greater reduction in the odds of CKD progression among patients with mild to moderate CKD and higher B12 levels. Funding: Government funding (National Key Research and Development Program of China).
AB - Rationale & Objective: In populations with folic acid fortification or supplementation, the main nutritional determinant of total homocysteine levels is vitamin B12 (B12) status. We aimed to evaluate the modifying effect of B12 levels on the association between folic acid treatment and chronic kidney disease (CKD) progression. Study Design: A post hoc analysis of an interventional trial. Setting & Participants: This is a post hoc analysis of 1,374 hypertensive adults with mild to moderate CKD and B12 measurements at baseline from the kidney disease substudy of the China Stroke Primary Prevention Trial (CSPPT), conducted in 20 communities in Jiangsu province in China, a region with low folate consumption. Interventions: Assignments to a double-blinded daily treatment of enalapril, 10 mg, and folic acid, 0.8 mg; or enalapril, 10 mg, alone. Outcomes: The primary outcome was progression of CKD (defined as a decrease in estimated glomerular filtration rate [eGFR] ≥ 30% and to a level of <60 mL/min/1.73 m2 if baseline eGFR was ≥60 mL/min/1.73 m2; or a decrease in eGFR ≥ 50% if baseline eGFR was <60 mL/min/1.73 m2; or kidney failure). Results: Mean baseline eGFR in this study was 86.1 ± 20.5 (SD) mL/min/1.73 m2. Median treatment duration was 4.4 years. Among participants with higher baseline B12 levels (≥248 pmol/L), compared to enalapril alone, enalapril–folic acid treatment was associated with an 83% reduction in the odds of the primary outcome (OR, 0.17; 95% CI, 0.07-0.40). However, among those with baseline B12 levels < 248 pmol/L (metabolic B12 deficiency), there was no significant group difference in the primary outcome (OR, 1.21; 95% CI, 0.51-2.85). The interaction between B12 level and folic acid treatment was significant (P = 0.001). Limitations: The analysis is post hoc and event rate is low. Conclusions: Folic acid treatment was associated with a greater reduction in the odds of CKD progression among patients with mild to moderate CKD and higher B12 levels. Funding: Government funding (National Key Research and Development Program of China).
KW - B12 deficiency
KW - CKD progression
KW - Vitamin B
KW - chronic kidney disease (CKD)
KW - eGFR decline
KW - enalapril
KW - estimated glomerular filtration rate (eGFR)
KW - folic acid supplementation
KW - hyperhomocysteinemia
KW - hypertension
KW - nutrition
KW - renal function decline
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U2 - 10.1053/j.ajkd.2019.07.020
DO - 10.1053/j.ajkd.2019.07.020
M3 - Article
C2 - 31629573
AN - SCOPUS:85073984878
SN - 0272-6386
VL - 75
SP - 325
EP - 332
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 3
ER -