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��ࡱ�>��	z}����y��������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������	��0�6bjbj����	4�����s.+�������[[[[[����ooo8��s�o(�-CCCZB���'(((((($]*��,>$([�ZZ��$([[CC9(�"�"�"�V[C[C�'�"��'�"�"�"C����@:�	���o!f�"�'O(0(�"=-�".=-�"�"�=-[n#|���"�����$($(�"���(������������������������������������������������������������������������=-���������	!:	Title: Influence of Intravenous and oral Vitamin C prescription on serum oxalate among hemodialysis patients
1-Alireza Shariati 2-Mohammad Mojerlo 3-Gholamreza Veghari 4-Hamid Asayesh 5- Hamidreza Joshaghani 6- Moslem Hesam 7- Mahdis Shariati 8-Masoumeh Baset 
1,6,7,8, Msc and Faculty member of Golestan University of Medical Sciences
2- MD, Nephrologists, Assistant professor of Golestan University of Medical Sciences
3- PhD candidate and Faculty member of Golestan University of Medical Sciences 
4- Msc, and Faculty member of Qum University of Medical Sciences
5- PhD, Clinical Biochemistry, Associated professor of Golestan University of Medical Sciences

Corresponding Author: Gholamreza Veghari 
Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, IRAN
Email: HYPERLINK "mailto:grveghari@yahoo.com"grveghari@yahoo.com


Abstract:
Background &Objective: Vitamin C consumption is necessary to compensate for its deficiency in hemodialysis patients, but the excessive use raised  concerns  about increased levels of serum oxalate and oxalosis. This study was performed to compare the influence of intravenous and oral vitamin C consumption on serum oxalate among hemodialysis patients in 5th Azar hospital in Golestan (north of Iran). METHODS: In the randomized control trial (RCT), Seventy five hemodialysis patients were selected via convenience methods. They were randomly allocated into controls (n = 25), oral vitamin C (OAA) group (n = 25) and intravenous vitamin C (IAA) group (n = 25). After dialysis session (three times weekly) patient took 300 mg intravenous vitamin C in IAA group and orally 500mg vitamin C in OAA group for 8 weeks. Serum oxalate was examined before and after therapy. SPSS 16.0 software was used for the statistical analysis. Chi-square and ANOVA were used for comparing groups. The P-value less than 0.05 was considered as statistical significant. 
RESULTS: There was no significant difference among three groups based on mean of serum oxalate before and after intervention. After intervention, mean value of serum oxalate was not significantly increased in IAA and OAA groups compared to control group. A mean difference of serum oxalate before and after IAA was not statistically significant. Mean of serum oxalate before and after intervention significantly increased in two intervention groups (P<0.05). CONCLUSION:  In hemodialysis patients the procedure of vitamin C supplementary associated with the serum oxalate level. Serum oxalate level unchanged in injected method but it is significantly increased in daily oral vitamin C supplementary. 
KEYWORDS: Vitamin C, Hemodialysis, Serum Oxalate, 

Introduction:
Calcium oxalate deposition in the tissues may develop in patients with inherited disorders of oxalate metabolism or can occur to other disease (1). One of them is chronic renal failure that resulted to secondary oxalosis syndrome (2). Oxalorasis is potentially a risk factor for metabolic disease like as atherosclerosis (3,4). Vitamin C depletion during dialysis period and its deficiency was reported in some studies (5,6). Vitamin C as an important antioxidant can be decrease the endothelial disorders by inhibition of lipid proxidation which is common in these patients. Hypertension and cardiovascular disease will occur as a consequence of endothelial disorders (5).
Scurvy is common in chronic renal failure patients because of the restriction of food intake and depletion of vitamin C during dialysis (7). Although, some studies carried out to determine the association between vitamin C and serum oxalate level, but they are comprehensively focused on intravenous vitamin C supplementation (6,8). However, vitamin C release iron from ferritin, but generally not recommended for iron deficient patients.  Thereby, the determination of appropriate dose of it for preventing scurvy and hyperoxalouria in hemodialysis patients is necessary. 
The main aim of this study is the comparison of serum oxalate variation between intravenous and oral prescription of vitamin C in hemodialysis patients.

Material and Methods: 
This was a randomized control trial (RCT) that established on the 75 hemodialysis patients for two months in 5th Azar hospital in Gorgan (a capital city in the north of Iran). Hemodialysis patients who had in Hb<11 gr /dl and no consumption vitamin C supplement included in this study. The patients randomly allocated in three groups (each group 25 cases). The first group as intravenous vitamin C(IAA) was injected 300 mg vitamin C after dialysis session for three times in a week, in the second group as oral vitamin C (OAA) were fed 500 mg after dialysis session for three times in a week and third group as a control group, not interfered  during study (Control). All patients received standard treatment for anemia. To ensure taking any vitamin C supplement, two weeks has been considered as wash out before interaction(9). 
The serum oxalate level was measured both before and after treatment period (two months interval). We drowned 5 ml arterial blood before and after treatment period and stored in caped laboratory polystyrene tubs. Oxalate was immediately measured by enzymatic method using MARK Kit in clinical laboratory. SPSS 16.0 software was used for the statistical analysis. Chi-square and ANOVA were used for comparing groups. The P-value less than 0.05 was considered as statistical significant. Written informed consent was received from all cases.
Clinical trial registration:
This study was approved by the Ethics Committee of Golestan University of Medical Sciences and registered at the Iranian Registry of Clinical Trials with IRCT21306115864N3.
Results:
The mean� standard deviation of age and hemodialysis duration were 56.9�14.1 years and 61.3�44.8 months, respectively and statistical differences was not significant among them. Diabetes and hypertension were the main causes of renal failure ( Table 1). 
Before intervention, the serum oxalate levels were not significant among three studies groups. Compared with control group, the serum oxalate in IAA and OAA was not significant after intervention (2 months).
In spite of, the level of serum oxalate increased up 30 �gr/dl in IAA group, differences were not significant before and after intervention. In OAA, the level of serum oxalate significantly increased 79 �gr/dl after intervention (P=0.006). The comparison of serum oxalate among three groups was not significant after intervention. Table 2.
Discussion: 
Vitamin C plus iron supplement has been descript in hemodialysis patients (9,10). On the other hand, more intake of vitamin C has been increased the serum oxalate, risk of CVD, infectious disease and boon disorders (10,3). In the present study, the level of serum oxalate was not significant in control group compared with OAA and IAA groups after intervention. However in OAA, the serum oxalate significantly increased after intervention. 
Similar to our results, the variation of serum oxalate was not remarkable after injection vitamin C up 300 mg during 8 weeks treatment (8). Ono (9) in a 6-month study on the dialysis patients found the positive association between vitamin C serum concentration and serum oxalate level in 46 patients who gradually intake 500,100, 50 and 0 mg /day vitamin C during study. 
Our study is shorter than of above study and dissimilarity of our results could be due to differences in duration and procedure treatment of patients..
Serum oxalate significantly increased both in oral and in intravenous vitamin C groups with 750 mg description weekly (10). In a 2-month clinical trial among dialysis patients the statistical significant difference in oral group (125 mg intake per day) compared to intravenous group (500 mg injected after dialysis at three times weekly) were observed (11). The positive association has been found between vitamin C consumption and serum oxalate during three months study (12). 
Our study is not completely according to above studies both in kind of supplement and treatment duration which are affected on serum oxalate serum.
Low sample size, short time study and lack of calculated food intake are the limiting factor in our study. 
Conclusion: 
The procedure of vitamin C supplementary associated with the serum oxalate level in hemodialysis patients. Serum oxalate level unchanged in injected method but it is significantly increased in daily oral vitamin C supplementary. In regard to easy use of intravenous supplementary of vitamin C in dialysis patients, this procedure can be recommended for compensation of vitamin C deficiency. Furthermore study is necessary to determine the association between vitamin C and serum oxalate level in a long time treatment.
Acknowledgment: 
The authors would like to thank the medical and administrative staff of the 5th Hospital for their valuable assistance during the field work, also the Research Deputy of the of Golestan University of Medical Sciences is thanked for the supporting this project financially.

References:    
1- Alkhunaizi A, Chan L. Secondary oxalosis: a cause of delayed recovery of renal functional in the setting of acute renal failure . J am societ Nephrol 1996 7:2320-2360.
2-Pru C,Eaton J,Kjellstrand C.Vitamin c intoxication and hyperoxalemia in chronic hemodialysis patient.Nephrol 39 1985:39(2):112-116
3- Thmpson C. Relationship Between vitamin C intake an increasing oxalosis. Seminars in Dialysis 1988, 1(2):94-98.
4- Ogawa Y,Machida N, Masahide J, Gakiya M, Chinen Y,Oda M, et al.Major factors modulation the serum oxalic acid level in hemodialysis patients. Frotiers in Bioscience 2004 Sep; 9:2901-2908.
5- Melendez O. Intravenous vitamin C for Erythropoietin resistance Patient. Semin Dial 2002; 13:335-360.
6-Descombres E, Hanck AB,Fellay G. Water soluble vitamins in chronic hemodialysis patients.Kideny Int 1993;43:1319-1328.
7-Singer R, Rhodes HC, Chin G, Kulkarni H, Ferrari P. High prevalence of ascorbate deficiency in an Australian peritoneal dialysis population. Nephrology (Carlton). 2008 Feb;13(1):17-22.

8-Tarng D,Wei Y,Huang T,Kuo T, Yang W.Intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia.Kidney Inter 1999 ;55:2477-2486.
9- Ono K. Secondary hyperoxalemia caused by vitamin c supplementation in regular hemodialysis patients .Clin Nephrol 1986; 26:239-243.
10-Chan D,Irish A,Dogra G,Efficacy and safety of oral versus intravenous ascorbic acid for anemia in hemodialysis  atients.Nephrol 2005;10:336-340.
11-Kalantar-zadeh K,Kopple JD, Deepak S, Block D, Block G. Food intake characteristics of hemodialysis patients 1as obtained by food frequent questionnaire. J Ren Nutr 2002; 12:17-31
12 - Canvese C,Petrarulo M,Massarenti P, Berutti S, Fenoglio R,Pauletto D ,et al. Long � term ,intravenous vitamin c leads to plasma calcium oxalate supersaturation in hemodialysis patients.Clin Nephrol 1989;31:31-34.


Table 1: Characteristics of patients included in a clinical trial study in Gorgan hospital 5th Azar (N=75). 
P-valueControl IAAOAAStudding groups 25 (13 male, 12 female) 25 (13 male, 12 female)25 (13 male, 12 female)Number of participants0.78756.2�17.155.7 � 17.556.9 �14.4Age (year)0.83059.4�38.665.8� 44.958.7�51.7Duration of Hemodialysis The cause of renal failure10910Diabetes (29)1099Hypertension(28) 5106Others  (21)      OAA= Oral vitamin C          IAA= Intravenous vitamin C 

Table 2: The comparison of serum oxalate level among three group studies before and after intervention (�mol/L) 
P-valueAfter 
Mean (SD)Before
Mean (SD)Studding groups0.070.225(0.077)0.225(0.035)IAA0.0060.288(0.133)0.209(0.041)OAA0.2450.224(0.057)0.205(0.037)Control 0.0660.056P- Value                               OAA= Oral vitamin C          IAA= Intravenous vitamin C








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