Elsevier

Nutrition

Volume 53, September 2018, Pages 103-108
Nutrition

Applied nutritional investigation
Relationship between plasma levels of homocysteine and the related B vitamins in patients with hemodialysis adequacy or inadequacy

https://doi.org/10.1016/j.nut.2018.02.004Get rights and content

Highlights

  • Water-soluble vitamins (e.g., folate, vitamins B6 and B12) and homocysteine might be lost during hemodialysis (HD), but it is unclear whether the loss of these vitamins is associated with plasma homocysteine concentration before and after HD treatment, especially in well-dialyzed patients.

  • Plasma vitamin B12 rather than plasma folate and vitamin B6 was negatively associated with plasma homocysteine in HD patients before and after receiving HD treatment regardless of dose dialysis or taking B-vitamin supplementation.

  • This significant association of vitamin B12 and homocysteine seemed not to be attributed to insufficient intake or excessive loss in dialysate but could be due to impaired vitamin metabolism. Vitamin B12 seemed to be a significant factor in relation to plasma homocysteine concentration in HD patients.

Abstract

Objectives

Hemodialysis (HD) with dialysis adequacy could increase the excretion of B vitamins (folate, vitamin B6, and B12) and raise the plasma level of homocysteine. Here we determined the associations of plasma homocysteine with B vitamins in patients with HD adequacy or inadequacy.

Methods

We recruited 68 patients who had received HD treatments (three times a week, 4 h each). Based on the individual's hemogram and quarterly urea reduction rate (Kt/V), patients were pooled into one of the following two groups: the first group with dialysis adequacy (Kt/V > 1.2, n = 48) and the second with dialysis inadequacy (Kt/V ≤ 1.2, n = 20). We also recorded the anthropometric date of each patient and their biochemical data and dietary intakes. Plasma levels of homocysteine, cysteine, folate, pyridoxal 5′-phosphate (PLP), and vitamin B12 were measured twice, once before and once after HD.

Results

The plasma levels of homocysteine, cysteine, folate, PLP, and vitamin B12 dropped significantly at the end of HD. The plasma levels of vitamin B12 were negatively correlated with the plasma levels of homocysteine, both pre- and post-HD, and in both groups regardless of dialysis adequacy or inadequacy. In contrast, plasma levels of folate and PLP were not correlated with homocysteine at both pre- or post-HD in both groups.

Conclusions

The plasma level of vitamin B12, but not folate or vitamin B6, was negatively correlated with that of homocysteine both before and after HD treatment, and regardless of dialysis adequacy or inadequacy.

Introduction

Dialysis treatment can be lifesaving for patients with end-stage renal disease waiting for kidney transplantation. Hemogram and quarterly urea reduction rate (Kt/V, where K is urea clearance, t is dialysis time, and V is urea distribution volume) are indicators of the adequacy of dialysis [1]. The Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guideline for Hemodialysis (HD) Adequacy (2015 update) recommended for patients a minimum delivered Kt/V of 1.2 per HD session for three weekly sessions [2]. Well-dialyzed patients benefit from improved life quality, better survival, and enhanced nutritional status compared with those with dialysis inadequacy [3], [4]. However, during HD, because of the high-flux and more permeable membrane dialyzers, nutrients might be lost, in particular small and middle molecular weights of water-soluble vitamins (e.g., folate, vitamin B6) [5]. It is unclear whether the loss of these vitamins after HD treatment in HD patients is associated with adverse clinical outcomes (i.e., hyperhomocysteinemia), especially those patients with dialysis adequacy.

Hyperhomocysteinemia is common in HD patients [6], [7], [8]. Increased homocysteine levels may induce excessive production of reactive oxygen species and may cause cardiovascular diseases, leading to higher morbidity and mortality in patients with end-stage renal disease [9], [10], [11], [12]. Homocysteine is metabolized through two pathways. Folate and vitamin B12 are both involved in the remethylation of homocysteine metabolism, whereas pyridoxal 5′-phosphate (PLP, the physiological coenzyme form of vitamin B6) acts as a coenzyme during transsulfuration in the homocysteine metabolism. Because B vitamins (folate, vitamins B6 and B12) are required for homocysteine metabolism, the loss of B vitamins during HD treatment in these patients may raise homocysteine levels [7], [13], [14], resulting in increased oxidative stress and higher risks of cardiovascular disease.

Those in the dialysis population without supplementation are more likely to develop deficiency in B vitamins [15], [16], [17]. Among B vitamins, folate (MW: 441 daltons) and vitamin B6 (MW: 245 daltons) have lower molecular weights and might be more easily removed during HD than vitamin B12, which is larger (MW: 1355 daltons). This is particularly true with the use of high-flux and more permeable dialyzers [5], [7]. Because homocysteine may also be removed by the HD treatment [5], it is unclear whether the loss of B vitamins during dialysis treatment or which kind of B vitamin is more critically associated with plasma homocysteine. The purpose of this study was to determine whether the changes of B vitamins were linked with the changes of homocysteine concentrations before and after HD sessions in patients with or without dialysis adequacy.

Section snippets

Study design and sample size calculation

This study had a cross-sectional design. A sample size of at least 62 participants allowed the detection of a significant correlation (coefficient ≥0.35) between B vitamins and homocysteine levels with a power of 80% and a two-sided test with an α of .05. A total of 68 participants were enrolled, exceeding our recruitment goal.

Patients

Patients were on chronic HD using a high-flux membrane dialyzer (Fresenius 4008 S dialysis systems, Bad Homburg, Germany), three times a week, 4 h each, at the Center of

Results

Table 1 shows the demographic characteristics and hematologic measurements of the 68 HD patients. Of these patients, 48 belonged to the dialysis adequacy group (Kt/V value ranged from 1.21 to 1.83), and 20 to the dialysis inadequacy group (Kt/V value ranged from 0.9 to 1.2). None of them was in a drinking habit, and only one in the dialysis inadequacy group was in a smoking habit. The etiologies of renal disease leading to HD were mainly diabetic nephropathy, chronic glomerulonephritis, uremia,

Discussion

HD treatment could improve quality of life and survival and reduce adverse clinical outcomes of HD patients [3], [4]. The dose and process of dialysis might reduce plasma levels of B vitamins. Although our patients did not consume enough dietary B vitamins, at least one third of them did take supplements of folic acid, vitamin B6, or vitamin B12. As a result, almost none of our patients displayed deficiencies of B vitamins at the pre-HD sessions. As folate and vitamin B6 were removed by the

References (30)

  • National Kidney Foundation

    KDOQI clinical practice guideline for hemodialysis adequacy: 2015 update. National Kidney Foundation

    Am J Kidney Dis

    (2015)
  • Peritoneal dialysis study group: adequacy of dialysis and nutrition in continuous peritoneal dialysis: association with clinical outcomes

    J Am Soc Nephrol

    (1996)
  • G. Schulman

    The dose of dialysis in hemodialysis patients: impact on nutrition

    Semin Dial

    (2004)
  • J. Heinz et al.

    Washout of water-soluble vitamins and homocysteine during haemodialysis: effect of high-flux and low-flux dialyser membranes

    Nephrology

    (2008)
  • C. van Guldener et al.

    Homocysteine and renal disease

    Semin Thromb Hemost

    (2000)
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    This study was supported by Taichung Veterans General Hospital, (TCVGH-1077302 B), Taiwan.

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