The Relationship between Folic Acid and Vitamin B12 Serum Levels with High Sensitivity C-reactive Protein and Homocysteine in Chronic Hemodialysis Patients: A Cross-sectional Study
Keywords:
Folic acid, vitamin B12, cardiovascular, mortality, morbidity, hsCRP, CKD, chronic hemodialysisAbstract
Background: Folic acid (FA) and vitamin B12 treatment have been routinely prescribed to lower serum homocysteine levels and to reduce inflammation. However, no study has been conducted to determine serum folic acid (SFA) and vitamin B12 (B12) levels in patients who have twice-weekly hemodialysis. The aim of our study was to assess serum folate and B12 levels in chronic hemodialysis patients and their relationship with hsCRP and homocysteine levels. Methods: Our study was a cross-sectional study involcing patients who had twice-weekly hemodialysis in Dr Cipto Mangunkusumo National Hospital Jakarta, Indonesia. Predialysis blood samples were taken to measure SFA, B12, homocysteine and hsCRP levels. Patients with medical conditions affecting the assays were excluded. Spearman correlation was used to compare variables. Results: Eighty subjects enrolled in this study. Among those of non-given folic acid and vitamin B-12 supplementation, only 3.85% of subjects had low folic acid levels, and none had low vitamin B12 levels. A moderate negative correlation between serum folic acid and homocysteine level (p≤0.001; r=-0.42) and a weak correlation between serum vitamin B12 and homocysteine level (p=0.009; r=-0.29) was found. Among the high-risk cardiovascular group (CRP>3, n=49), there is a moderate negative correlation between serum folic acid and homocysteine level (p≤0.001; r=-0.561) and a weak negative correlation between vitamin B12 and homocysteine level (p=0.018; r=-0.338). Conclusion: There is a significant negative correlation between serum vitamin B12 and folic acid with homocysteine levels, especially in high-risk cardiovascular group.References
Xu X, Qin X, Li Y, et al. Efficacy of folic acid therapy on the progression of chronic kidney disease: the renal substudy of the china stroke primary prevention trial. JAMA Intern Med 2016;176(10):1443-50. doi: 10.1001/jamainternmed.2016.4687
Azalea M, Andayani TM, Satibi. Analisis biaya pengobatan penyakit ginjal kronis rawat inap dengan hemodialisis di rumah sakit. Jurnal Manajemen dan Pelayanan Farmasi 2016;6(2):141-50.
Suhardjono. Hemodialisis: prinsip dasar dan pemakaian kliniknya. In: Setiati S, Alwi I, Sudoyo AW, et al., eds. Buku Ajar Ilmu Penyakit Dalam. Jakarta: Interna Publishing 2014:2192-96.
Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: global dimension and perspectives. The Lancet 2013;382(9888):260-72. doi: 10.1016/s0140-6736(13)60687-x
Parfrey PS, Foley RN. The clinical epidemiology of cardiac disease in chronic renal failure. J Am Soc Nephrol 1999;10:1606-15.
Team IRR. 10th report of Indonesian renal registry. Jakarta: Indonesian Renal Registry, 2018.
Nand M, Sharma M, Mittal N. Prevalence of hyperhomocysteinaemia in chronic kidney disease and effect of supplementation of folic acid and vitamin B12 on cardiovascular mortality. JIACM 2013;14(1):33-36.
Tamadon MR, Jamshidi L, Soliemani A, et al. Effect of different doses of folic acid on serum homocysteine level in patients on hemodialysis. Iran J Kidney Dis 2011;5(2):93-96.
Qin X, Huo Y, Langman CB, et al. Folic acid therapy and cardiovascular disease in ESRD or advanced chronic kidney disease: a meta-analysis. Clin J Am Soc Nephrol 2011;6(3):482-8. doi: 10.2215/CJN.05310610
Amini M, Khosravi M, Baradaran HR, et al. Vitamin B12 supplementation in end stage renal disease: a systematic review. MJIRI 2015;29(167):1-8.
Bazeley J, Bieber B, Li Y, et al. C-reactive protein and prediction of 1-year mortality in prevalent hemodialysis patients. Clin J Am Soc Nephrol 2011;6(10):2452-61. doi: 10.2215/CJN.00710111
Li Y, Zhong X, Cheng G, et al. Hs-CRP and all-cause, cardiovascular, and cancer mortality risk: A meta-analysis. Atherosclerosis 2017;259:75-82. doi: 10.1016/j.atherosclerosis.2017.02.003
Hwang YC, Morrow DA, Cannon CP, et al. High-sensitivity C-reactive protein, low-density lipoprotein cholesterol and cardiovascular outcomes in patients with type 2 diabetes in the EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial. Diabetes Obes Metab 2018;20(3):654-59. doi: 10.1111/dom.13136
Hassan K. Association of low potassium diet and folic acid deficiency in patients with CKD. Ther Clin Risk Manag 2015;11:821-7. doi: 10.2147/TCRM.S83751
Jamison RL, Hartigan P, Kaufman JS, et al. Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: A randomized controlled trial. JAMA 2007;298(10):1163-70. doi: 10.1001/jama.298.10.1163
Jardine MJ, Kang A, Zoungas S, et al. The effect of folic acid based homocysteine lowering on cardiovascular events in people with kidney disease: systematic review and meta-analysis. BMJ 2012;344:e3533. doi: 10.1136/bmj.e3533
Wrone EM. Randomized Trial of Folic Acid for Prevention of Cardiovascular Events in End-Stage Renal Disease. Journal of the American Society of Nephrology 2004;15(2):420-26. doi: 10.1097/01.asn.0000110181.64655.6c
Chang TY, Chou KJ, Tseng CF, et al. Effects of folic acid and vitamin B complex on serum C-reactive protein and albumin levels in stable hemodialysis patients. Curr Med Res Opin 2007;23(8):1879-86. doi: 10.1185/030079907X218077
Heinz J, Kropf S, Domrose U, et al. B vitamins and the risk of total mortality and cardiovascular disease in end-stage renal disease: results of a randomized controlled trial. Circulation 2010;121(12):1432-8. doi: 10.1161/CIRCULATIONAHA.109.904672
Righetti M, Serbelloni P, Milani S, et al. Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients. Blood Purif 2006;24(4):379-86. doi: 10.1159/000093680
Righetti M, Ferrario G, Milani S, et al. Effects of folic acid treatment on homocysteine levels and vascular disease in hemodialysis patients. Med Sci Monit 2003;9(4):37-42.
Vianna ACA, Mocelin AJ, Matsuo T, et al. Uremic hyperhomocysteinemia: A randomized trial of folate treatment for the prevention of cardiovascular events. Hemodial Int 2007;11(2):210-16. doi: doi:10.1111/j.1542-4758.2007.00171.x
Trimarchi H, Schiel A, Freixas E, et al. Randomized trial of methylcobalamin and folate effects on homocysteine in hemodialysis patients. Nephron 2002;91:58-63.
Hulley SB, Cummings SR, Browner WS, Grady D, Newman TB. Designing clinical research : an epidemiologic approach. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013. Appendix 6C, page 79
Fehrman-Ekholm I, Lotsander A, Logan K, et al. Concentrations of vitamin C, vitamin B12 and folic acid in patients treated with hemodialysis and on-line hemodiafiltration or hemofiltration. Scand J Urol Nephrol 2008;42(1):74-80. doi: 10.1080/00365590701514266
Information NCfB. Vitamin B12, CID=25102581. PubChem Database, 2019.
Azar A, Canaud B. Hemodialysis system. In: Azar AT, ed. Modelling and control of dialysis systems. Berlin: Springer-Verlag 2013:99-166.
Clase CM, Ki V, Holden RM. Water-soluble vitamins in people with low glomerular filtration rate or on dialysis: a review. Semin Dial 2013;26(5):546-67. doi: 10.1111/sdi.12099
Soohoo M, Ahmadi SF, Qader H, et al. Association of serum vitamin B12 and folate with mortality in incident hemodialysis patients. Nephrol Dial Transplant 2017;32(6):1024-32. doi: 10.1093/ndt/gfw090
Yousuf O, Mohanty BD, Martin SS, et al. High-sensitivity C-reactive protein and cardiovascular disease: a resolute belief or an elusive link? J Am Coll Cardiol 2013;62(5):397-408. doi: 10.1016/j.jacc.2013.05.016
Pastore A, Angelis SD, Casciani S, et al. Effects of folic acid bfore and after vitamin B12 on plasma homocysteine concentrations in hemodialysis patients with known MTHFR genotypes. Clin Chem 2006;52(1):145-48.
Downloads
Published
How to Cite
Issue
Section
License
Copyright
The authors who publish in this journal agree to the following requirements:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0) that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors can enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) before and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work. (See The Effect of Open Access)
Privacy Statement
The names and email addresses entered in this journal site will be used exclusively for the stated purposes of this journal and will not be made available for any other purpose or to any other party.
