The Effects Of Vitamin B₁₂ And Folic Acid In The Treatment Of Hyperhomocysteinemia In Patients With End-Stage Renal Disease

The Effects of Vitamin B12 and Folic Acidin the Treatment of Hyperhomocysteinemia in Patientswith End-Stage Renal DiseaseAbstractHyperhomocysteinemia is frequently found in patients with chronic renal failure (CRF) in recent years. It has been demonstrated in lots of studies to be an independent risk factor for atherosclerotic cardiovascular disease (CVD). Since CVD is a major cause of morbidity and mortality in the end-stage renal disease (ESRD) patients, it is necessary to prevent and treat hyperhomocysteinemia. Folic acid (FA), vitamin B12 (B12) and B6 (B6) are the main vitamin substrates or cofactors for homocysteine (Hcy) metabolism. Foreign studies have found that supplement with B-vitamin, such as FA, can reduce the plasma Hcy levels in ESRD patients. But most of the studies were uncontrolled, and they seldom observed the effects of different combinations of B-vitamin, especially the effect of using B12 alone. Our trial has investigated the plasma Hcy, FA and B12 concentrations in patients with ESRD, used pharmacologic doses of FA and B12 with different administration pathways and combinations to study their effects on treating hyperhomocysteinemia.We utilized FPJA, ICA and MEIA methods respectively to detect the plasma Hcy, FA and B12 concentrations of healthy subjects (w=45) and ESRD patients (n=202), established their reference ranges and compared the levels between ESRD patients and healthy subjects, patients on hemodialysis-6-(HD)(n=189) and peritoneal dialysis (PD)(n=l3), patients with CVD(n=23)and without CVD(n=179),Which perfOrmed by Independent Samples T Test.The correlations between plasma Hcy and FA levels, Hcy arid Bl2 levels wereanalyZed by Bivariate. Lastly, the hemodialytic patients withhyperhomocysteinema were randomly divided into 6 grouPs to be treateddifferently as follows: (l) oral administration of Bl2 0.5mg/d, (2) oraladministration of FA l5mg/d, (3) both(l)and(2), (4)intramuscularinjection of Bl2 0.5mg/d, (5) both(2)and(4), (6)blank-controlledwith none of them. After 4 weeks, the plasma Hcy, FA and BI2 levels weredetected repeatedly. We compared the levels before and after treatment ineach group (Paired SamPles T Test), compared the reducing rate of Hcylevels (One-way ANOVA and LSD) and the cure rae ofhyperhomocysteinemia (Chi-Square Test) among 6 grouPs. Values of Pr0.05 were used to define statistical significance.The results revealed that: (1) The mean p1asma Hcy level of our healthysubects was7.97i2.65pmol/L, so the upper limit of reference range was13.27pmol1. The prevalence of hyperhomocysteinemia in ESRD patients.was 86%, their mean plasma Hcy concentration was 23.26l9.57 pmol/L,Which was significantly higher than that of healthy subjects(Prt0.001). Themean plasma Hcy level ofhemodialytic patients was significantly higher thanthat of peritoneal dialytic patients(24.72i7.74 vs.l5.98 f4.54pmol/L, Pwt0.0l ), The Hcy levels in ESRD patients with CVD were significantly higher, than those without CVD(26.58 f 5.3l vs.20.55 i 6-33llmol/L,Pwt0.05).(2)The mean plasma FA level of the healthy subects was 21.2f7.6- 7 -nmol/L, the normal range was 6.0--36.4 nmol/L. ESRD patients had a meanlevel of 20.6 l 8.8 nmol/L,which was not different to normal. The plasma FAconcentrations were normal or elevated mildly in most of ESRD patients,only tWo HD patienis had FA insufficiency The mean FA level had nosignificant difference between HD and PD patients(l9.7 l 8.5 and 22. l l 7.9nmol/L), but the mean FA 1evel in patients with CVD was lower than that ofwithout CVD(l8.9f9.2 vs.23.6i 8.3 nmol/L, P<0.05).At the same time,we found that there was a reverse correlation between plasma Hcy and FAlevels(rr -0.34l, P wt0.01).(3)The mean plasma Bl2 level of healthy subjects was 484I l79 pmol/L,and the normal range was l26--842 pmol/L. There was no difference betweenESRD patients (52l l237 pnloUL)and healthy subects. The plasma Bl2'levels were normal or rised slightly i...