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ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 1  |  Page : 190-195

Plasma vitamin C concentration in chronic kidney disease: Comparison between diabetic and nondiabetic patients


1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Shibin Al Kom, Egypt
2 Department of Microbiology, Faculty of Medicine, Menoufia University, Shibin Al Kom, Egypt
3 Department of Nephrology, Alamrya General Hospital, Alexandria, Egypt

Date of Submission31-Jul-2016
Date of Acceptance23-Oct-2016
Date of Web Publication25-Jul-2017

Correspondence Address:
Saad M Mohammed Elgengaihy
Tanta, Gharbia, 31511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.211501

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  Abstract 


Objective
The aim of the study is to evaluate the relationship between renal functions and plasma vitamin C concentration in nondiabetic and diabetic patients with chronic kidney disease.
Background
A decreased plasma level of vitamin C has been reported to be associated with an increased risk of cardiovascular morbidity and mortality. Here, we sought to determine the vitamin C status of patients with chronic kidney disease and the pathophysiological role of vitamin C in these patients.
Patients and methods
A total of 50 patients were included in the study and classified into two groups: group I, patients with chronic kidney disease with diabetes and group II, patients with chronic kidney disease without diabetes. The relationship between renal function and plasma vitamin C concentration was evaluated, as well as the effect of diabetes on this relationship.
Results
Statistical comparison revealed a significant statistical increase in the mean value of vitamin C level in the group II compared with group I (P ≤ 0.001). Also, there was a significant positive correlation between vitamin C level and both weight and estimated glomerular filtration rate in the patients, whereas there was a significant negative correlation between vitamin C level and each of serum creatinine level, blood urea level, albumin–creatinine ratio, and glycosylated hemoglobin level in the patients.
Conclusion
Renal dysfunction was associated with a decreased level of plasma vitamin C in patients with chronic kidney disease. Diabetic patients showed a lower level of vitamin C at any given estimated glomerular filtration rate compared with nondiabetic patients.

Keywords: albumin–creatinine ratio in urine, blood urea, estimated glomerular filtration rate, HbA1c, serum creatinine, vitamin C


How to cite this article:
Elkafrawy NA, Dawood AA, Rizk MS, Mohammed Elgengaihy SM. Plasma vitamin C concentration in chronic kidney disease: Comparison between diabetic and nondiabetic patients. Menoufia Med J 2017;30:190-5

How to cite this URL:
Elkafrawy NA, Dawood AA, Rizk MS, Mohammed Elgengaihy SM. Plasma vitamin C concentration in chronic kidney disease: Comparison between diabetic and nondiabetic patients. Menoufia Med J [serial online] 2017 [cited 2019 Jun 19];30:190-5. Available from: http://www.mmj.eg.net/text.asp?2017/30/1/190/211501




  Introduction Top


Chronic kidney disease involves progressive and irreversible loss of renal function, which begins with the appearance of proteinuria and elevated serum creatinine levels, representing a decrease in the glomerular filtration rate (GFR), and finally results in complete loss of kidney function, that is, end-stage renal disease [1].

Diabetic nephropathy is the leading cause of end-stage renal disease in the USA. The progression of kidney disease in patients with diabetes can take many years, and interventions such as glycemic control, blood pressure control, and inhibition of the renin–angiotensin–aldosterone system have been shown to slow this progression. Despite the implementation of these strategies, the number of patients with diabetes who ultimately develop end-stage renal disease remains high [2].

A decreased plasma level of vitamin C has been reported to be associated with an increased risk of cardiovascular morbidity and mortality. There is a need to determine the vitamin C status of patients with chronic kidney disease and the pathophysiological role of vitamin C in these patients [3].

Decreased vitamin C level may cause endothelial dysfunction by an increase in oxidative stress in nondiabetic patients with chronic kidney disease [3].

Experimental lines of evidence have been accumulated that denote vitamin C has beneficial effects on endothelial function and formation of atherosclerotic lesions [4]. The study aimed to evaluate the relationship between renal functions and plasma vitamin C concentration in nondiabetic and diabetic patients with CKD.


  Patients and Methods Top


This study was carried out on 50 patients selected from the inpatient department and outpatient clinics of the Internal Medicine Department, Nephrology Division, in Menofia University Hospital. The selected participants provided consent for participation in the study before they were subjected to examinations and investigations, and the study was approved by the Ethics Committee of Menofia University Hospital. The study was carried out from October 2013 to December 2015.

The selected participants were classified into two groups: group I, patients with chronic kidney disease with diabetes and group II, patients with chronic kidney disease without diabetes. All patients met the following criteria: estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m 2; no previous history of myocardial infarction, heart failure, or stroke within 6 months; and not taking vitamin C.

All patients were subjected to the following.

Assessment of history

Assessment of history was performed for all participants in the study group, with a special focus on age and sex of the patients, duration of diabetes mellitus (DM), and the presence or absence of specific diabetic complications and treatment.

Complete clinical examination

All participants were subjected to a complete clinical examination including measurement of weight and signs of diabetic complications, including signs of diabetic nephropathy (e.g., edema usually around the eyes in the mornings and later, may be generalized edema) and diabetic neuropathy (i.e., sensory loss to light touch, vibration, and temperature). Abnormalities in more than one test of peripheral sensation are more than 87% sensitive in detecting the presence of neuropathy. Patients who have lost 10-g monofilament sensation are at considerably elevated risk of developing foot ulceration [5].

Laboratory investigations included the following:

Glycosylated hemoglobin

HbA1c levels depend on the blood glucose concentration, that is, the higher the glucose concentration in blood, the higher the level of HbA1c. Levels of HbA1c are not influenced by daily fluctuations in the blood glucose concentration but reflect the average glucose levels over the previous 6–8 weeks.

Kidney function tests

These include examination of blood urea nitrogen and serum creatinine level.

Estimated glomerular filtration rate

GFR was estimated by Cockroft–Gault equation (ml/min):



Albumin–creatinine ratio

The morning 10-ml midstream urine samples were collected and were centrifuged at 3000 rpm for 10 min before analysis. Microalbuminuria levels were measured using an autoanalyzer (Beckman Coulter Synchron CX 9; Beckman Coulter Inc.). Urine creatinine levels were measured in the first urine of the morning using a spectrophotometer (Clinical Chemistry Analyzer 7), and the ratio was calculated as the urinary albumin–creatinine ratio (A/C).Microalbuminuria ranges between 30 and 300 mg/g creatinine.

Plasma vitamin C level

Plasma vitamin C is found as ascorbic acid as well as its oxidized form, dehydroascorbate. Both forms are biologically active. In our vitamin C assay, an oxidation is induced before analysis so that both forms are measured. A dose–response curve of the absorbance unit (optical density at 492 nm) versus concentration is generated using the values obtained from the standard. The concentration of the patient sample is determined directly from the linear standard curve.

Plasma sample was not diluted and was used directly for the sample preparation. A 2-ml blood sample was taken in a tube with EDITA and centrifuged at 3000 rpm for 5 min. Moreover, 200 ml of the supernatant (plasma) was added to 200 ml of meta-phosphoric acid and centrifuged for 30 min at 4°C at 10 000 rpm, and the supernatant then stored at −20°C. Samples were kept in a cool and dark place.

Reference range is 4–15 mg/l.

Statistical analysis

All data were collected, tabulated, and statistically analyzed using SPSS 19.0 for windows (SPSS Inc., Chicago, Illinois, USA) and MedCalc 13 for windows (MedCalc Software bvba, Ostend, Belgium).

Two types of statistics were done: (i) descriptive analysis (numbers, parentage, mean, SD, and range) and (ii) analytical analysis. The analytical analysis includes (a) correlation (r): The correlation analysis is used to know the relation between variables. It aims at expressing the changes that occur in one variable which follow the changes in other variables. (b) χ2-test: it is used to compare between two or more qualitative variables contingency table or r × c comple × 2 × 2 in table. (c) P value: P less than 0.05 indicates significant difference and P less than 0.01 indicates high significant difference. (d) t-Test.


  Results Top


There was no significant difference between the two groups studied regarding age, sex, and weight (P = 0.843, 0.247, and 0.117, respectively).

Plasma vitamin C level in group I ranged between 0.6 and 13.0 mg/l with a mean value of 5.013 ± 3.825, whereas in group II, it ranged between 1.4 and 21.5 mg/l with a mean of 10.656 ± 6.433; there was a significant statistical increase in the mean value of vitamin C in group II compared with group I (P < 0.001) [Table 1] and [Figure 1].
Table 1 Vitamin C value in both studied groups

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Figure 1: Vitamin C value in both studied groups.

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Statistical analysis revealed that there was no significant statistical difference between both groups regarding blood urea concentration, serum level of creatinine, and rate of e-GFR (P = 0.917, 0.663, 0.50, respectively).

Urine A/C ratio of patients of group I ranged between 60 and 400 μg/mg with a mean value of 215.76 ± 118.45 μg/mg, whereas in group II, it ranged between 45 and 260 μg/mg with a mean of 124.52 ± 72.0 2 μg/mg. Statistical analysis revealed that there was significant statistical difference between both groups regarding A/C ratio (P = 0.002) ([Table 2] and [Figure 2].
Table 2 Albumin-creatinine ratio in both studied groups

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Figure 2: Albumin–creatinine ratio in both studied groups.

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Glycosylated hemoglobin concentration in patients of group I, patients with chronic kidney disease with diabetes, ranged between 7.4 and 10%, with a mean value of 8.27 ± 0.76%, whereas in group II, patients with chronic kidney disease without diabetes, it ranged between 4 and 5.4%, with a mean of 4.81 ± 0.30%. There was significant statistical difference between both groups of the study regarding HbA1c concentration (P = 0.000) [Table 3] and [Figure 3].
Table 3 HbA1c level in both studied groups

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Figure 3: HbA1c level in both studied groups. HbA1c, glycosylated hemoglobin.

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Statistical analysis revealed that there was no significant statistical difference between female and male patients of group I regarding weight, age, creatinine level, urea level, and HbA1c level, whereas there was more significant statistical difference regarding A/C ratio, vitamin C level, and eGFR [Table 4].
Table 4 Comparison between female and male patients in group I regarding vitamin C level, age, weight, serum creatinine level, blood urea level, eGFR, and HbA1c level

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Statistical analysis revealed that there was no significant statistical difference between female and male patients of group II regarding weight, age, creatinine level, urea level, HbA1c level, vitamin C level, eGFR, and A/C ratio [Table 5].
Table 5 Comparison between female and male patients in group II regarding vitamin C level, age, weight, serum creatinine level, blood urea level, eGFR, and HbA1c level

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Statistical analysis revealed that there was a significant positive correlation between vitamin C level and both weight and eGFR in the patients as shown in [Table 6]. Statistical analysis revealed that there was a significant negative correlation between vitamin C level and each of serum creatinine level, blood urea level, A/C ratio, and glycosylated hemoglobin level in the patients as shown in [Table 6]. Statistical analysis revealed that there was no significant difference between vitamin C level and age [Table 6].
Table 6 Correlation between vitamin C level and patient variables of the study

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  Discussion Top


CKD is an emerging public health problem and one of the most powerful predictors of premature cardiovascular disease [6].

In unsupplemented patients with CKD, several deficiencies in various components of antioxidant defense mechanisms have been demonstrated, including reduced plasma vitamin C concentration. Vitamin C is a primary antioxidant that directly neutralizes radical species as well as an essential nutrient required for the formation of collagen and normal immune function [3].

Ascorbic acid is involved in the formation and repair of collagen, the development of bones and teeth, amino acid metabolism, the synthesis of hormones, and wound healing. It facilitates iron absorption and utilization [7].

DM is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels [5].

Diabetic nephropathy is the leading cause of end-stage renal disease in the USA. The progression of kidney disease in patients with diabetes can take many years, and interventions such as glycemic control, blood pressure control, and inhibition of the renin–angiotensin–aldosterone system have been shown to slow this progression. Despite the implementation of these strategies, the number of patients with diabetes who ultimately develop end-stage renal disease remains high [2].

The aim of this study was to evaluate the relationship between renal functions and plasma vitamin C concentration in nondiabetic and diabetic patients with CKD.

This study was conducted at Menofia University Hospital on 50 patients who all had CKD, with 25 diabetic patients (group I) and 25 nondiabetic patients (group II).

In our study, plasma vitamin C level was 5.013 mg/l in diabetic patients (group I) and 10.656 mg/l in nondiabetic patients (group II), with a significant low level in group 1 compared with group 2.

Takahshi et al. [3] found in their study that the mean vitamin C level was 4.5 mg/ml in diabetic patients (group I) and 6.2 mg/ml in nondiabetic patients (group II), with no significant difference between the levels in both studied groups; this is because both groups had CKD. Dietary restrictions of fresh fruits and vegetables to avoid hyperkalemia are likely to be responsible for the decrease in plasma vitamin C concentration, because vitamin C cannot be synthesized endogenously and plasma vitamin C levels are largely dependent on dietary intake of the vitamin. Proteinuria is another important factor that causes an increase in urinary loss of vitamin C [8].

We found no statistical significant difference between female and male patients of group I regarding weight, age, creatinine level, urea level, and HbA1c level, whereas there was significant statistical increase in vitamin C level and eGFR and reduction of A/C ratio in male than in female patients; as in patients with equal weight and equal investigations of urea and creatinine there is more eGFR in males than in females.

There was no significant statistical difference between female and male patients of group II regarding weight, age, creatinine level, urea level, HbA1c level, vitamin C level, e-GFR, and A/C ratio.

Sargeant and colleagues found in their study that there was no significant statistical difference between female and male patients regarding age and HbA1c level. This was in agreement with our study [9].

Our results revealed statistically positive correlation between vitamin C level and both weight and eGFR in the patients, whereas there was negative correlation between vitamin C level and each of serum creatinine, blood urea, A/C ratio, and glycosylated hemoglobin in the patients.

Takahashi et al. [3], reported that there were significant relationships between eGFR and urinary protein excretion in patients of their study; these could explain the relationship between decreased vitamin C concentration and renal dysfunction, which was in agreement with our study.

Takahashi et al. [3] reported that there was a negative correlation between vitamin C level and creatinine level, albumin–globulin ratio, and glycosylated hemoglobin concentration, which was in agreement with our study, whereas no relation between vitamin C level and blood urea, and this disagreed with our results.

Sargeant et al. [9] found in their study that there was a negative correlation between vitamin C level and glycosylated hemoglobin concentration, which was in agreement with our study.

Fennell found in his study that a combination of insulin and vitamin C may help stop diabetes-induced blood vessel damage in people with poor blood glucose control, and according to new research published in The Journal of Clinical Endocrinology and Metabolism, halting this damage could help prevent a host of complications, such as chronic heart failure, kidney disease, and eye disease [10].

Afkhami-Ardekani and Shojaoddiny-Ardekani [11] found in their study that supplementation with 1000 mg/day of vitamin C in addition to the normal diet and treatment schedule may help in improving plasma glucose and lipid profile in patients with type 2 diabetes.

Harding and Wareham [12] found in their study that there was a significant inverse association between vitamin C levels in the blood and the risk of getting diabetes, also showing that vitamin C, as well as a high intake of vegetables and fruits, may have protective effects against diabetes.

Bhatt et al. found in their study that oral vitamin C supplementation is found to be effective and has potential implications for the prevention of further complications in patients with DM [13].

Daniel [14] found in his study that combining insulin with vitamin C stops blood vessel damage in type 1 diabetics.

Kotb and colleagues found in their study that oral supplementation of vitamin C as an adjuvant with antidiabetic drugs may have particularly attractive therapeutic effect in the treatment of type II DM. Studies with a larger sample size and longer follow-up period together with measurement of other related antioxidant levels may be needed to yield more beneficial data on the role of the antioxidant system in the clinical course of type II DM [15].


  Conclusion Top


Renal dysfunction was associated with a decreased level of plasma vitamin C in patients with CKD, and diabetic patients showed a lower level of vitamin C at any given eGFR compared with nondiabetic patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Bhatt JK, Thomas S, Nanjanmj MJ. Effect of oral supplementation of vitamin c on glycemic control and lipid profile in patients with type 2 diabetes mellitus. source. Int J Pharm Pharmaceut Sci 2012; 4:524.  Back to cited text no. 13
    
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Kesavadev J, Saboo B, Sadikot S, Das AK, Joshi S, Chawla R, et al. Unproven Therapies for Diabetes and Their Implications. Adv Ther 2017; 34:60–77.  Back to cited text no. 14
    
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    Figures

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