Association of serum vitamin B12 and folate with mortality in incident hemodialysis patients

Abstract

A B S T R A C TBackground: Vitamin B12 (B12) and folate are essential vitamins that play important roles in physiological processes. In the general population, many studies have evaluated the association of these vitamins with clinical outcomes, yet this association in hemodialysis (HD) patients remains unclear. Methods: We examined the association of serum folate and B12 with mortality in a 5-year cohort of 9517 (folate) and 12 968 (B12) HD patients using Cox models with hierarchical adjustment for sociodemographics, comorbidities, and laboratory variables associated with the malnutrition and inflammation complex syndrome. The associations of baseline B12 and folate (separately) with all-cause mortality were evaluated across five categories of B12 [<400 (reference), 400-<550, 550-<650, 650-<750 and !750 pg/mL] and folate [<6.2, 6.2-<8.4, 8.4-<11 (reference), 11-<14.3 and !14.3 ng/mL]. Results: The study cohort with B12 measurements had a mean 6 standard deviation age of 63 6 15 years, among whom 43% were female, 33% were African-American, and 57% were diabetic. Higher B12 concentrations !550 pg/mL were associated with a higher risk of mortality after adjusting for sociodemographic and laboratory variables. However, only lower serum folate concentrations <6.2 ng/mL were associated with a higher risk of all-cause mortality when adjusted for sociodemographic variables [adjusted hazard ratio (95% confidence-interval): 1.18 (1.03-1.35)]. Conclusions: Higher B12 concentrations are associated with higher all-cause mortality in HD patients independent of sociodemographics and laboratory variables, whereas lower folate concentrations were associated with higher all-cause mortality after accounting for sociodemographic variables. Further studies are warranted to determine the optimal B12 and folate level targets in this population.

Association of Plasma Concentration of Vitamin B12With All-Cause Mortality in the General Population in the Netherlands

“…11 Another strength of this study is the implementation of a robust method of plasma concentration of vitamin B 12 quantification. The accuracy of the assay that we used has been evaluated using the vitamin B 12 World Health Organization International Standard. 33 Moreover, it has been reported that the Elecsys Vitamin B 12 assay is not affected by anti-intrinsic factor antibodies, enhancing the reliability of this assay.…”

“…Vitamin B 12 is a hydrosoluble vitamin that plays a substantial role in 1-carbon metabolism. The 1-carbon pathway is involved in several biological functions beyond fetal development, such as mitochondrial metabolism, immune response, and nucleotide homeostasis in nonproliferative tissues.…”

“…The 1-carbon pathway is involved in several biological functions beyond fetal development, such as mitochondrial metabolism, immune response, and nucleotide homeostasis in nonproliferative tissues. 1 While the deleterious effects of vitamin B 12 deficiency, such as anemia, neuropsychiatric symptoms, and other clinical manifestations, are well established, 2 the potential association of high plasma concentrations of vitamin B 12 with adverse health outcomes has not been fully explored. 3 Indeed, a potential association of high vitamin B 12 plasma concentrations with excess mortality has been assessed in elderly [3][4][5][6][7][8][9] and hospitalized 10,11 populations, but it has not been explored in the general population, to our knowledge.…”

“…An association of high plasma concentrations of vitamin B 12 with increased risk of all-cause mortality has been reported among patients undergoing dialysis treatment. 12 It has also been found that impaired renal function is associated with high plasma concentrations of vitamin B 12 .…”

“…12 It has also been found that impaired renal function is associated with high plasma concentrations of vitamin B 12 . 13,14 Furthermore, it has been found that combined supplementation of folic acid, vitamin B 6 , and vitamin B 12 results in more rapid decline of renal function and an increase in occurrence of vascular events in patients with diabetic nephropathy. 15 Taken together, these findings underscore the importance of further exploration of a possible role of chronic kidney disease (CKD) in the association of plasma concentrations of vitamin B 12 with all-cause mortality.…”