Effect of Vitamin B12 Levels on the Association Between Folic Acid Treatment and CKD Progression: A Post Hoc Analysis of a Folic Acid Interventional Trial

Youbao Li, J. David Spence, Xiaobin Wang, Yong Huo, Xiping Xu, Xianhui Qin

Research output: Contribution to journalArticle

Abstract

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).

Original languageEnglish (US)
Pages (from-to)325-332
Number of pages8
JournalAmerican Journal of Kidney Diseases
Volume75
Issue number3
DOIs
StatePublished - Mar 2020

Keywords

  • B12 deficiency
  • CKD progression
  • Vitamin B
  • chronic kidney disease (CKD)
  • eGFR decline
  • enalapril
  • estimated glomerular filtration rate (eGFR)
  • folic acid supplementation
  • hyperhomocysteinemia
  • hypertension
  • nutrition
  • renal function decline

ASJC Scopus subject areas

  • Nephrology

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