Nguyen Thj Hoa vd Dtg Tgp chi KHOA HQC & C 6 N G NGHE 165(05): 37-42
N 6 N G fib H O M O C Y S T E I N H U Y £ T TlTOfNG 6 B E N H NHAN L O C MAU CHU K t BXrOC BO SUNG ACID FOLIC VA VITAMIN NHOM B
Nguyin Thi Hoa'*, Hodng Nggc Kham*
Duong Hlng Thdi',Tr^n Bao Nggc' 'Trudng Dgi hgc Y Dugc - DH Thdi Nguyen.
^ Benh vi?n A Thdi Nguyen TOM T A T
Tdng homocystem (Hey) huylt tuong rat thu6ng g5p d benh nhSn suy thgn man Igc mdu chu ky (LMCK) vd Id ylu tl gia tdng nguy co bfnh tim mgch. Vi vdy, dieu Ui giam Hey huylt tuong la rat cdn thiet. Myc tieu: Ddnh gia kit qua lam giam nlng dd homocystein huylt tuong d BN suy than mgn LMCK bSng bo sung acid folic, vitamin BI2, vitamin B6 Dli tu-OTig vd phuo'ng phap nghien cfru: nghien ciiu md td, cdt ngang Uen 63 BN suy th|n man Igc mdu chu ky (BN STM LMCK), chia thinh 2 nhdm: nhdm 1 gim 32 BN STM LMCK don thuin. Nhom 2: ^Im 31 BN STM LMCK kit hgp vdi bo sung vitamin. Kit qud: Sau 3 thdng LMCK don thudn, ndng df Hey huylt tucmg Id 39,0±I9,4 \imo\lL, khong c6 su khic biet so vdi thdi dilm ban dlu (38,4±20,5
^mol/L). Sau 3 thdng LMCK ket hgp vdi bl sung vitamin, nlng do Hey huylt hrong Id 28,8±13,2
^mol/L, gidm c6 y nghta so vdi thdi diem trudc bo sung vitamin (39,0±17,0 |imol/L). So vdi thdi dilm trudc bl sung, nlng df Hey huylt tuong giam trung binh Id 10,22±5,96 |imol/L, gidm 28,4±6,9%. Kit ludn: Bl sung vitamm c6 hifu qud Idm giam nong df Hey huylt mong.
Tir khda: suy thgn mgn, homocystein, Igc mdu chu ky, binh lim mgch, viim man tinh DAT VAN DE
Tang homocystein (Hey) huyet tuong la mgt trong nhii'ng ylu to nguy ea bfnh tim mach.
Hey Id aeid amin khong can thiet doi vdi eo thf, dugc hinh thdnh tir qua trinh chuyen hda ciia methionin. Hey duge chuyen hda theo hai eon dudng Id vgn chuyin nhdm sulfua va methyl hda. Qua trinh methyl hda can ca chat la aeid folic, dugc xiic tdc bdi enzym methionine synthetase c6 vitamin B ^ la chat cung phoi hgp vdi enzym nay. Phdn dng vgn chuyen nhdm sulfua can enzym cystathion synthase cd coenzyme la vitamin B^.
0 BN LMCK thudng cd thilu hyt vitmin 8,2 do tinh trgng dinh duang kem. Hon nQ'a, ngudn thiic an giau vitamin B12 thudng cd hdm lugng kali eao nen rlt nguy hilm doi vdi BN, vi vay BN LMCK thudng phai hgn ehe nhirng thiic an ndy. Vitamin B]2, acid folic la chdt cd trgng lugng phdn tii trung binh nen cung cd thi bi Ioai bd qua Igc mau d nhiing BN sii dung mang lge cd hifu suat sieu Igc cao. Vi vgy, nong df Hey huylt tuang thudng tang d BN LMCK [9].
Tel 0982502072. Email: hoanguyeniM74®yahoc
Tang Hey cd lifn quan den xo viia mach va lam gia tdng nguy co benh tim mgch. Vi vdy, vifc dieu trj gidm Hey d nhiing BN ndy Id rat can thiet de gidm nguy co benh tim mach. 0 cgng dong, viee dilu tri giam 25% Hey lien quan din giam 11% nguy co benh mach vanh vd gidm 19% nguy ca dot quj [7].
Trfn thf gidi cd kha nhieu nghien ciiu vf hieu qua ciia viec dieu trj gidm Hey bdng acid folic, vitamin Be, vitamin B12 [3], [ 5], [7].
Nghifn Cliu cua Azadibakhsh ve hifu qua dieu tri giam Hey cua acid folic, vitamin B12 dan thudn hoae kit hgp, ket qua cho thdy viec su dyng kit hgp aeid folic va vitamin B12 co hieu qua giam Hey han so vdi viec su dyng don thuan [3]. Ngodi acid folic vd vitamin B12, tde gia Heinz cdn bo sung them vitamin Be trong thdi gian 6 thdng d BN STM LMCK, kit qua cho thay sau bl sung cac vitamin tren trong thdi gian 6 thang, hifu qud dieu tri giam Hey dugc cdi thifn rd rft [5].
Tgi Vift Nam, tdc gia Huynh Van Nhugn (2008) da nghien ciiu vl hifu qua cua dilu tri giam Hey d BN STM LMCK. Tuy nhien, thdi gian bfl sung vitamin trong nghien ciiu tren la 37
Nguyin Thi Hoa vd Dtg Tgp chl KHOA HQC & CONG NGHE mflt thang. Vgy, vifc keo dai thai gian bo
sung vitamin cd eai thifn han nlng dg Hey d BN STM LMCK hay khong? Df trd ldi cau hdi frfn chiing tdi thyc hifn df tai nay vdi myc tieu:
Ddnh gia kit qud lam gidm nlng do homocystein huylt tuang d BN suy thgn man LMCK bdng bo sung acid folic, vitaminB12, vitamin B6.
DOI TUCJNG vA PHU'ONG P H A P NGHlfiN CUD
Doi tirgng nghien cuu
Doi tugng nghifn ciiu gom: 63 BN STM LMCK 3 Idn/tudn, 4 gid/lan tgi khoa Hdi siic Bfnh vign A Thai Nguyen, BN duge ehia thdnh 2 nhdm:
Nhdm 1: gflm 32 BN STM LMCK don thudn.
Nhdm 2: gdm 31 BN STM LMCK kit hgp vdi bo sung 30mg acid folic/ngdy vd lOOmg vitamin Be/ngay, uong vdo buoi sdng vd chieu trudc khi an 30 phut hdng ngay, kit hgp vdi tif m bdp 1 mg Bn sau khi LMCK xong.
Thdi gian nghien citu: Tix thdng 9/2015- 7/2016
Dia diem nghien ciru
Khoa Huylt hgc bfnh vign A Thai Nguyfn.
Khoa Hoi siic bfnh vifn A Thai Nguyen.
Khoa Xet nghifm Bfnh vifn Trudng Dai hgc Y khoa Thai Nguyfn.
Pbiroug phap nghifn ciru: mfl ta cat ngang.
Thiet bj nghien ctiu
May xet nghifm huylt hgc ty dflng Celltac F.^
May xet nghiem sinh hda ty dgng OLYMPUS AU480.
Hda chdt do hdng NIKHON KOHDEN, BECKMAN COULTER cung cap.
Chi tieu nghien ciru
- Mgt sl ddc dilm ldm sang nhu tufli, gidi, thdi gian LMCK, chi sd khfli eo thi (BMI), huyet dp tdm thu (HATT) vd huyet dp taiii truang (HATTr).
Djnh lugng ndng do homocystein huyet tuang bdng phuang phdp miln djch do dg dye. Binh thudng nong do homocystein<l^
pmol/L.
- Dinh lugng ure, creatinin huyet tucmg theo qui trinh chuan, thuc hifn trfn mdy AU 400 tgi khoa Sinh hda bfnh vign A Thai Nguyen. . - Tflng phan tieh tl bao mdu ngogi vi trfn n # huylt hgc tu dgng tgi khoa Huylt hgc benh vifn A Thai Nguyfn,
Phdn loai tang homocystein huylt tuang theo phan logi ciia tdc gid Arora [3]:
Homocsytein (jimol/L) Binh thudng TSng nhe TSns vira TSng cao 5-<l5 15-<30 30-100 >100 Xu Iy so lieu
Xii Iy sl lifu theo phuang phdp thflng ke y hgc su dyng phdn mem Stata 10.
KET QUA NGHIEN CUXJ Dgc diem nhdm nghien ciiu
Bang 1. Mgt so dgc diim chung nhom nghiin cicu DSc diem
Tuoi (nSm) GiiSi Nam: n (%) Na; n (%) Tiiai gian LM (tiling) BM1(X ±SD) HATT (mmHg) ( X ±SD)
Nh6m 1 (n=32) 51,2±i5,2
13(40,6) 19 (59,4) 43,4±20,2 20,8±2,4 I42,2±27,9
Nh6m 2 (11=31) 49,7±12,4
16(51,6) 15 (49,4) 49,2±14,7 20,8±1,4 146,7±17,9
P
>0,05
>0,05
>0,05
>0,05
•1 ll i
I 1
HATTr (mmHg) (X ±SD) 38
Nguyin Thj Hoa v^ Dtg Tgp chi KHOA HOC & CONG NGH? 165(05): 37 - 42 Nhan xet: Khflng cd su khac bift vl tuoi, gidi, thdi gian LMCK, chi sl khoi ca thi cung nhu huyet dp.
Nong dg homocystein va mgt sl chi sl huyet hgc a nhdm nghien ciiu
Bang 2. Nong dg homocystein huyit tirong tnrac vd sau bo sung vitgmin Homocystein
(timol/L) Tnrdc bo sung (1) Sau 3 M n g (2)
Tliaydoi X ±SD Giam "^^
Tine "<°''°' Nli6m 1 (n-32)
38,4±20,9 39,0±19,4 Tang:0,58±2,15
6(18,8) 4,5±3,2 26(81,2) 4,6±5,1
Nh6m 2 (n-31) 39,0±17,0 28,8±13,2 Giam: 10,22±5,96
29 (93,5) 28,4±6,9 2 (6,5) i,92±l,99
P
>0,05
<0,05
<0,05
<0,05 ' Nhan xet: Hai nhdm nghifn ciiu kha tuang dong vl nlng do Hey huylt tuang tgi thdi dilm trudc
! bd sung vitamin. Sau ba thdng bd sung vitamin theo phac do, ndng dg Hey huyft tuang thap han cd y nghTa so vdi thdi diem trudc bo sung eiing nhu thap han cd -^ nghTa so vdi nhdm khflng dugc B bd sung vitamin tgi cung thdi diem, nong dg Hey huyft tuong giam trung binh la I0,22|imol/L, ty oi le gidm trung binh la 28,4%. 6 nhdm khong dugc bd sung vitamin, khflng co su khac bift ve
«i nlng do Hey huylt tuong tgi hai thdi dilm, ndng dg Hey huylt tuang trung binh tdng 0,58 fimol/L, tang trung binh 4,6%.
c. Bdng 3. Ndng dg ure vd creatinin huyit luang tru&c vd sau bd sung vitamin Ji Chi sl Nh6m 1 (n=32) Nh6m 2 (n=31) p I'jj Trudc bo sung (1) 27,8±13,3 31,2±7,6 >0,05
'^^ Sau 3 thang (2) 30,0±9,l 28,3±7,0 >0,05 p(l,2) >0,Q5 >0,05
(mmol/L)
Creatuiin Trade bd sung (I) 997,0±4i2,3 1035,2±232,2 >0,05 Sau3th4ng(2) 998,8±384,5 102l,l±218,7 >0,05 tt^'""'^) p(l,2) >0,05 >0,05 Nhgn xet: Khdng ed su khde bift cd y nghTa ve nong dp ure, creatinin huyet tuang giiia hai nhom nghien ciiu tai thdi diem trudc va sau bo sung vitamin 3 thdng, Khong cd sy khac bift vf ndng do L ure, creatinin huylt tuong tai thdi diem trudc vd sau bo sung vitamin d cd hai nhdm nghien ciiu.
Bdng 4. Mgt so chi so huyit hgc a nhom nghien cuu truac vd sau bo sung vitamin
'-
111 IJi
Hlng clu (T/L)
Hb (8%)
Hct(%) C h i s S Tmoc bo sung (1) Sau 3 tiling (2) P ( l , 2 ) Trade bo s u n g ( l ) Sau 3 thdng (2) P ( l , 2 ) Tmoc bo sung (1) Sau 3 tiling (2) P ( l , 2 )
Nil6m 1 (n-32) 3,i3±0,65 3,i5±0,49
>0,05 9,34±2,05 9,66±l,5i
>0,05 27,43±5,92 28,32±5,17
>0,05
Nh6m 2 (n=3r) 2,88±0,74 3,24±0,51
<0,05 9,11±2,37 9,89±1,64
<0,05 25,48±6,92 30,i8±4,89
<0,00!
P
>0,05
>0,05
>0,05
>0,05
>0,05
>0,05
Nhan xet: Khflng cd sy khde bift vl so lugng hong cdu, hemoglobin, hematocrit giiia hai nhdm 'T'nghien cihi tgi thdi dilm trudc bo sung vitamin. Sau bo sung vitamin 3 thang, d nhdm BN dugc
•^ bo sung vitamin, mgt so chi sfl huylt hgc dlu cao hon eo y nghTa so vdi thdi dilm trudc bfl sung,
" " 39
Nguyin Thi Hoa vo Dig Tgp chl KHOA HOC & CONG NGHE 165(05): 37-41 "1 BANLUAN
d BN LMCK tang 16 lan nguy ca tii vong do bfnh tim mgch [8]. Han niia, nguy ca phi dgi that trai, suy tim sung huyet va bgnh tim thieu mdu eye bg eung eao hon so vdi BN mde bfnh thgn man tinh giai dogn dau. Cd moi lifn quan gifta tang Hey huyet tuong vdi nguy co bfnh tim mgch d BN suy thgn giai dogn cuoi [9], [10]. Bd sung acid folic va vitamin dugc cho Id cd hifu qud Idm gidm Hey huyet tuang d nhiing BN ndy [6], [7], [8].
Trong nghifn ciiu eiia chung tdi, sau bo sung acid folic 30mg/ngay, vitamin B^ lOOmg /ngdy, uong hdng ngay kit hgp vdi tiem bap lmg Bi2 sau moi lan LMCK trong thdi gian 3 thang, ndng dg Hey huylt tucmg la 2S,8±13,2^moI/L, thdp han cd y nghTa so vdi thdi dilm trudc bfl sung, ndng dg Hey huyet tuong gidm trung binh Id 10,22±5,96 fimoI/L, giam 28,4±6,9%. Ci nhdm BN LMCK dan thuan, khflng cd sy khac bift cd "$ nghTa ve ndng df Hey huyet tuong tgi thdi diem trudc vd sau 3 thdng, nong dg Hey huyet tuong trung binh tang O,58±2,15nmol/L, tang 4,6±5,1.
Trong mgt thu nghifm lam sang ngau nhien cd doi chirng d 571 BN STM LMCK, BN dugc chia thanh 2 nhdm: nhdm I gom 372 BN dugc sii dyng vitamin vdi lilu vitamin Be 100 mg/ngay, vitamin B12 2mg/ngdy vd acid folic 40 mg/ngay; nhdm 2 gom 379 BN dugc sii dyng gid dugc. BN dugc bo sung vitamin trong thdi gian 3 thang va tiep tye duy tri din het 3 nam dau, ket qua thu dugc nhu sau: d nhdm BN sii dyng vitamin nong dg Hey huylt tuong tai thdi diem sau 3 thang, sau 1 nam, hai nam cOng nhu 3 nam deu gidm cd y nghia so vdi thdi dilm trudc bl sung. 6 nhdm BN sir dyng gid dugc, nong dp Hey huylt tuong khdng cd sy khde bift tgi cdc thdi dilm tren so vdi thdi dilm ban dau [6]. Ti If giam nflng dg Hey tgi thdi dilm sau 3 thdng la 25,8%.
Tae gia Chiu (2009) [4] da nghien ciiu d 75 BN STM LMCK ed bo sung acid folic va vitamin 6,2 trong thdi gian 3 thdng, BN dugc 40
chia thanh 3 nhdm: nhdm 1 dugc bl sung acid folic 3mg/tuan, tifm tTnh mgch; nhdm 2 dirge bfl sung vitamin Bn Img/tuan; nhom 3 dirge sii dyng kit hgp ca hai logi tren. Kit qud thu dugc nhu sau: nlng do Hey huylt tuong giam CO '^ nghTa d ea 3 nhdm so vdi thdi dilm tnrdc bl sung, ^ If giam ndng do Hey tuong iing d 3 nhdm Id 16,4%, 29,3% va 38,9%. Vifc bl sung kit hgp aied folic va vitamin B12 cd hieu qud gidm nflng dg Hey huyft tuang han so vdi sii dyng don thuan.
Tdc gia Heinz (2010) [5] da nghien cihi d 327 BN STM LMCK, dugc bl sung 5 mg acid folic, 50 pg vitamin B12 va 20 mg vitamin 86, BN dugc sii dyng 3 ngay/tuan vdo thdi diem BN den LMCK, thdi gian su dyng trung binh la 2,1 ndm. Ket qua thu dugc nhu sau: Nflng dg Hey huyet tuong gidm tgi thdi dilm sau bo sung vitamin 6 thang so vdi thdi diem tnrdc bo sung, nlng do Hey huylt tuong gidm trung blnh la 10,4 pmol/L.
Nghifn Cliu ciia tac gid Nguyfn Minh Tri (2015) [2] d 54 BN LMCK dugc bl sung acid folic 5mg/ngdy, vitamin Be lOOmg/ngay va vitamin B12, 1 mg tiem sau mdi lan LMCK, kft qua cho thay: ndng do Hey huyet tuong sau bl sung 3 thdng gidm rd rft so vdi thdi difm trudc bo sung (13,32± 3,2 p,mol/L so vdi 28,84i: 21,37 ^moI/L). Vdi lieu lugng vitamin va acid folic tuong ty ciia tac gia Nguyen Minh Tri (2015) [2], thdi gian bl sung la 4 tudn, ndng do Hey huyet tuong cung gidm ro rft so vdi thdi diem trude bd sung (16,02±3,54 pmol/L so vdi 28,25±10,06 pmol/L), ndng dfl Hey huyet tuong giam trung binh 12,23±8,94 umol/L, giam 39,79±I3,93%.
Higu qud giam Hey huyet tuang trong nghien Cliu eiia chiing tfli thdp han so vdi cac nghien Cliu [1], [2]. Cd thi do trong nghien ciiu cua chiing toi miic do suy thgn, ndng do Hey huylt tuang tai thdi dilm nghien ciiu cao hon so vdi nghien eiiu [1], [2], thdi gian Igc mau lau han (trong nghien ciiu [2] cd 27,8% so BN LMCK<I nam, nghien ciiu ciia chung toi khdng cd BN ndo cd thdi gian LMCK< 2
Nguyen Thi Hoa vd Dtg Tgp chl KHOA HOC & CONG NGHE 165(05); 3 7 - 4 2 nam). Hifu qud giam Hey huyet t u o n g trong
nghien eiiu eiia chung tdi t u a n g t y n h u nghien eiiu ciia tac gid Heinz (2010) [5] va Jaminson (2007) [6].
Khflng chi eai thign ndng dg Hey huylt tuong, sau b l sung aeid folic va vitamin, mgt sd chi sd huyet hgc c u n g cdi thifn dang ke so vdi thai diem trudc b o sung, ket qud nghien Cliu eua chiing tdi eiing tuong ty nghifn eiiu eiia tdc gid N g u y e n Minh Tri (2015) [2].
K E T LUAN
N l n g do Hey h u y l t tucmg sau bo sung acid folic va vitamin 3 thang la 28,8±13,2nmol/L giam cd y nghTa so vdi thdi diem tru'dc bo sung vitamin (39,0±17,0 (imol/L), p<0,05.
Bfl sung vitamin cd hieu qud Idm giam nflng dg Hey huyet t u a n g .
T A I L I E U THAM K H A O 1. Huynh Van Nhugn (2009), Nghien aru biin ddi nong dg homocystein mdu vd hiiu qud diiu trj a BN sw thdn mgn chgy thgn nhdn tgo chu ky, Lugn dn tien sT Y hgc - Traong Dgi hgc Y Dugc - DH Hul.
2 Nguyin Minh Tri vd cs (2015), "Vai trd cua homocystein d BN lge thdn", Ky yeu Hgi nghi Khoa hgc Bfnh viin An Giang, tr. 103-110.
3. Azadibakhsh (2009), "Efficacy of Folate and Vitamin 8 1 2 m Lowering Homocysteine Concentrations in Hemodialysis Patients ", Saudi J. Kidney Dis. Transpl.. 20 (5), pp. 779-788.
4. Chiu YWl C. J., Hwang S. J„ Tsai J. C , Chen H, C. (2009), "Pharmacological dose of vitamin 812 is as effective as low-dose folinic acid in correcting hyperhomocysteinemia of hemodialysis patients", ,fie/j Fail.. 31 (4), pp. 278-283.
5. Heinz J., DomrOse U., Westphal S., Borucki K., Luley C , Neumann K. H., Dierkes J. (2010), "B vitamins and the risk of total mortality and cardiovascular disease in end-stage renal disease:
results of a randomized controiled trial.".
Circulation. 121 (12), pp. 1432-1438, 6. Jamison (2007), "Effect of Homocysteine Lowering on Mortality and Vascular Disease in Advanced Chronic Kidney Disease and End-stage Renal Disease A Randomized Controlled Trial", American Medical Association Journal, 298 (10), pp.1163-1170.
7. Jardme (2012), "The effect of folic acid based homocysteine lowering on cardiovascular events in people with kidney disease: systematic review and meta-analysis", B M J.. 244, pp. 212-230, 8. Nand (2013), "Prevalence of hyperhomocy steinaemia in chronic kidney disease and effect of supplementation of folic acid and vitamin 812 on cardiovascula mortality", JIACM20I3. 14(1): 33- 6. 14 (l),pp, 33-36.
9. Robinson K., Gupta A., Dennis V., et al (1996),
"Hyperhomocysteinemia confers an independent increased risk of atherosclerosis in end-stage renal disease and is closely linked to plasma folate and pyridoxine concentrations", Circulation. 94 (11), pp. 2743-8.
10. Sagheb M, M , Ostovan M, A., Sohrabi Z., et al. (2010), "Hyperhomocysteinemia and cardiovascular risks in hemodialysis patients", Saudi J. Kidney Dis Transpl. 21 (5), pp, 863-6
Nguyen Thj Hoa vd Dtg Tgp chi KHOA HOC & CONG NGHE 165(U5): 37 - ^
S U M M A R Y
PLASMA H O M O C Y S T E I N IN HEMODIALYSIS P A T I E N T S
W H O W E R E GIVEN SUPPLEMENTATION FOLIC A C I D A N D V I T A M I N B Nguyen Thi Hoa* , Hoang Ngoc Kham^
Duong Hong Thai',Tran Bao Ngoc' 'College of Medicine and Pharmacy - TNU,
'Thai Nguyen A Hospital Hyperhomocysteinemia is common in end stage renal disease. Objective: 1) Assess the effect homocysteine lowering of folic acid, vitamin 812, vitamin Be in hemodialysis patients. Method: A cross-sectional study of 63 hemodialysis patients, who divided into two groups. Group ]• Included 32 hemodialysis patients, not given daily supplementation of vitamin. Group 2: Included 31 hemodialysis patients, given daily supplementation of 30 mg folic acid, lOOmg vitamin Be and lmg of vitamin B12. Plasma Hey and some other tests were measured at baseline, at 3 months.
Result: At baseline, at 3 months, the plasma Hey in group 1 were 38,4±20.5 umol/L and 39.0±19.4 fimol/L, respectively. Plasma Hey levels decreased significantly in group 2, from 39.0±17.0 fimol/L to 28.8±I3.2 \imo\lL at 3 months (p<0.05) Conclussion: Daily supplementation of vitamin can be reduced plasma Hey levels.
Key word: End stage renal disease, homocystein, hemodialysis, cardiovascular, chronic inflammation
Ngay nh^n bdi: 05/4/2017, Ngay phdn bi$n: 19/4/2017, Ngdy duy^tddng: 12/5/2017 Tel- 0982 502072, Email: [email protected],
42
