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Essay: Vitamin C and chronic kidney disease

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The study was conducted in the city of Groningen, which is in the most northern province in the Netherlands. Participants with chronic kidney disease were selected for this study. The participants were divided in two groups, a predialysis and a kidney transplant group. All participants gave written informed consent. This study focussed on the vitamin C intake via food consumption and the vitamin C plasma concentration of the participants. The participants were being treated in the University Medical Centre Groningen (UMCG). All the participants were either patients at the nephrology policlinic or patients at the kidney transplant policlinic. To check whether the patients of the nephrology and kidney transplant policlinic were willing to participate they were approached by the nephrologist. If interested, they received a phone call with information about participation from a second physician whom they have not met before. After the participant signed the informed consent, blood samples, a 24 hour dietary recall and symptoms were inventoried. The participants were all examined on a regular policlinic appointment. There is only one measuring point and no intervention. Therefore it is a prospective observational cross-sectional small cohort study with quantitative data.

This study focussed primarily on the vitamin C intake via food consumption, the vitamin C plasma concentration and vitamin C related complaints. Besides these two primary variables, this study also did other laboratory measurements and examined the macronutrients intake and energy intake. The other laboratory tests consisted of: albumin, CRP, haemoglobin, TSAT, transferrin, and iron. The examined macronutrients are: protein, fat and carbohydrates. The energy-intake was also inventoried. The primary and secondary outcomes are all ratio variables except for the outcomes of the questionnaire of complaints which are ordinal variables and the primary kidney diseases and comorbidities which are nominal variables. The background characteristics: gender, smoking and comorbidities are nominal, BMI is ordinal and the weight, age and length are ratio variables. Three different measuring instruments were used for the data collection. A 24 hours dietary recall, a questionnaire of complaints and blood samples for the laboratory measurements. Table 1 gives an overview of the measured variables and the corresponding measuring instruments.

The study population consists of 47 participants with CKD who were divided in two groups with 22 participants in the predialysis and 25 in the kidney transplant group. The name of the participants is anonymized by using a numerical code. The collected data and blood samples are stored for ten years and the laboratory test results are stored for fifteen years. This study was approved by the Medical-ethical commission of the UMCG. The participants were asked in sequential order for this study. This means that the patient with the first policlinic appointment was asked to participate first and was included when a written informed consent was received and when the participant fitted the inclusion criteria. The inclusion criteria for the predialysis group were: 1) ≥18 years or older; 2) an ECC of 20 ml/min for at least three months. The inclusion criteria for the kidney-transplant group were: 1) ≥18 years or older; 2) an endogenous creatinine clearance (ECC) of >30 ml/min for at least three months; 3) the kidney transplant must have been performed at least six months ago. The used ECC values were based on the guidelines of the laboratory “Bijzondere Chemie” of the UMCG. The exclusion criteria were the same for both groups: 1) malabsorption; 2) gastrointestinal diseases; 3) oncological disorders. These exclusion criteria were compiled to eliminate their unwanted influence on the results of this study.

A third small group consisted of three HD patients. This group was used to try the 24 hour recall, laboratory tests and questionnaire of complaints out. In part two more HD patients will be included. The inclusion criteria for this group are: 1) at least three times a week four hours of haemodialysis (12 hours per week); 2) at least three months in treatment. The exclusion criteria are: 1) malabsorption; 2) gastrointestinal diseases; 3) oncological disorders.

Materials and method

All the measurements took place in a random order on the same day. This is because the vitamin C intake has to correspond with the vitamin C plasma concentration and the order is not important for the results. The 24 hours dietary recall took approximately 15 minutes and the questionnaire of complaints ten minutes. The examination of the blood samples usually took over a fortnight. All the participants were seen on the policlinic of the UMCG either on the nephrology or on the transplantation policlinic. The outcome of the 24 hours recall was measured in EvryDietist (programme for dietary analysis) and stored in SPSS 23. The outcomes of the questionnaire of complaints were directly stored in SPSS. The results of the laboratory tests were put in PoliPlus (database used by UMCG) and when available stored in SPSS.

24 hour dietary recall method

Dietary data was obtained by almost graduated dietitians using the 24 hour dietary recall method. The 24 hours dietary recall was used to examine energy intake, protein intake, carbohydrate intake, fat intake and the vitamin C intake via food consumption, and took approximately 15 minutes. The food- and beverage intake of the 24 hours before the policlinic appointment was collected and documented. This 24 hours dietary recall method was used to inquire the type of food, brand of food, amount of food and ways of preparation per eating session. It also obtained information about the usage of dietary supplements. For a better estimation of the portion size, pictures of different portions were shown as illustrations. Because the vitamin C concentration in the blood correlates with recent vitamin C intake, a 24 hours dietary recall method was used.23 In order to get a representative food- and beverage intake of the participants, the examined day had to be a weekday with a usual intake. To be sure of this, the participants were asked if it was a normal weekday with a usual intake, if this was not the case, the participant was excluded from this study. Energy intake was measured in kilocalories, and proteins, carbohydrates, fats in grams (g) and vitamin C in milligrams (mg). In appendix 2 an example of a 24 hours dietary recall form can be found. After the 24 hour dietary recall information about smoking habits, weight, height, date of birth and gender was obtained. To The body mass index (BMI) was calculated as weight in kilograms, divided by height in meters squared. Information about co morbidities was obtained from PoliPlus. The obtained information was calculated and examined in EvryDietist. Evrydietist works with the Nevotabel 2011. (bron). A vitamin C intake of ≤75 mg/day was considered as a low vitamin C intake.

Questionnaire of complaints

Face-to-face private interviews were conducted by almost graduated dietitians. The predefined questionnaire consisted of four main questions and sixteen sub questions. This questionnaire is based on the short-form health survey 36 (SF-26). The SF-36 is a standardized health survey which is widely used.24 The first questions examined the general health and their perception of their health. The other questions examined the presence and extent of complaints and symptoms. The examined complaints were based on symptoms that have been previously reported by patients with CKD. All the questions were multiple choice scale questions varying from one to five. Answer number one is experienced as the least severe and answer number five is experienced as the most severe. The questionnaire of complaints took approximately ten minutes. There was one question added to the questionnaire of complaints and three questions were dismissed. A question about muscle cramps was added, and the questions about muscle cramps in-between haemodialysis treatment or during treatment and shunt problems were removed. In appendix 3 an exact questionnaire of complaints can be found.

Laboratory measurements

 In the non-fasting participants, the blood samples were taken on the same day as the 24 hours recall and the questionnaire of complaints for determination of the vitamin C plasma concentration. Blood samples were conducted by using a venipuncture.  One blood sample of ten milliliter was taken together with five milliliter extra blood and stored an EDTA-bulb. EDTA functions as an anticoagulant which means preventing that the blood clots (coagulation).25 The blood samples were used for the examination of all the laboratory measurements. (Vitamin C plasma, albumin, CRP, TSAT, ferritin, iron, HB and PTH). The obtained blood samples were brought to the laboratory “Bijzondere Chemie” within two hours covered in ice. A high pressure liquid chromatography (HPLC) with a fluorescence detector was used for the examination of vitamin C plasma concentration. The vitamin C plasma concentration in µmol/l was calculated via a calibration curve and a line regression analysis. The blood samples were stored first and analyzed all at the same time. Quality checks were done at each measurement by taking control samples to check for standard outcomes. Each result was checked by a clinical chemist before reporting them into PoliPlus.

 Three blood samples were taken of the HD patients, one before hemodialysis, one sample halfway through the hemodialysis and one after the hemodialysis. Dialysate samples were also taken from the HD patients. One dialysate sample was taken 15 minutes after starting the hemodialysis, one after two hours, and the last one 15 minutes before the end of the hemodialysis.

A plasma vitamin C concentration of ≤10 µmol/l was considered as a vitamin C deficiency and a plasma vitamin C concentration of 10-≤35 µmol/l was considered as a vitamin C inadequacy. A plasma vitamin C concentration of >35 µmol/l was considered as adequate. A description of the vitamin C measurement protocol can be found in appendix 4.

Statistical analysis

Statistical Package of Social Sciences (SPSS 23 Inc. Chicago IL, USA) was used for the analysis off the data. All the data was stored in SPSS version 23. All variables were evaluated to be normally distributed according to the Shapiro-Wilks test and a normality plot. All performed statistical analysis were two tailed using a significance level of P 0.05. Age, length, BMI, weight and the macronutrients were normally distributed. All the laboratory test outcomes and the vitamin C intake were not normally distributed.

 There was no clear explanation for the outliers that have been found and therefore no outliers were removed from the database. There was no non-response but some of the laboratory tests have been impossible to perform due to errors while obtaining the blood samples obtained blood samples which were too small.  There were three missing values of the plasma vitamin C concentration, therefore all analyses with the plasma vitamin C concentration consist of 44 participants instead of 47 participants.  

For descriptive analysis the mean and standard deviation of the age, length, weight, and BMI of both groups were calculated. The mean and standard deviation were also calculated for carbohydrate intake, fat intake, protein intake, and energy intake. For the nonparametric variables the median and interquartile range (IQR) was calculated. These were albumin, CRP, haemoglobin, TSAT, ferritin, PTH, vitamin C intake and plasma vitamin C. The actual number of participants and percentages of the primary kidney diseases FSGS, ADPKD, urologic causes, nephritis and IgA nephropathy were calculated. The actual number and percentages were also calculated for gender, smoking, and the comorbidities, hypertension, DM2, and coronary heart and vessels diseases (CVD). The median and IQR was also calculated for the outcomes of the questionnaire of complaints.

Independent T-tests were performed to see if there was a difference between the predialysis and kidney transplant group in age, length, weight, BMI, gender, smoking, energy-intake, carbohydrate intake, protein-intake and fat intake. Mann-Whitney U tests were performed to see if there was a difference in the nonparametric variables between the predialysis and kidney transplant group. These were the laboratory test outcomes, primary kidney diseases and comorbidities.

The median and IQR per variable or question on the list of complaints was calculated for three groups, one group of participants with a vitamin C deficiency, one group of participants with a vitamin C inadequacy and one group of participants with an adequate plasma vitamin C concentration. Furthermore, the median and IQR of the vitamin C intake and plasma vitamin C concentration were calculated for the predialysis and kidney transplant group. The actual number of participants and percentage of participants with a vitamin C deficiency, vitamin C inadequacy and with a vitamin C intake below the minimum recommended intake were calculated for the predialysis and the kidney transplant group.

Subsequently Mann-Whitney U tests were performed to verify whether there was a statistical significant difference in vitamin C intake and plasma vitamin C concentration between the predialysis and kidney transplant groups. Mann-Whitney U tests were also performed to verify whether there was a significant difference in vitamin C intake and plasma concentration between men and women, smokers and non-smokers, participants with a BMI of ≤25 or above 25 and participants aged ≤65 or ≥65.

The median and IQR of albumin, CRP, haemoglobin and ferritin was calculated for three groups, the deficiency, inadequacy and adequate vitamin C concentration. Thereafter, Kruskall-Wallis H tests were performed to verify whether there was a difference between the three groups. If there was a significant difference, post hoc Mann-Whitney U tests were performed to verify between which groups the difference was.

Finally, some descriptive analyses were performed for the HD participants. The median of the vitamin C intake and plasma vitamin C concentration were calculated. Furthermore the median of the energy-intake, carbohydrate-intake, protein-intake and fat-intake were calculated.

Results

Participant characteristics.

A total of 47 participants were included in the final analysis. 22 predialysis and 25 kidney transplant patients. Three HD participants were analysed separately from the other participants. In the predialysis group were eight females and in the kidney transplant were ten females. The mean age was significantly different between both groups (P=0,011). The mean age of the kidney transplant group (65 ±9,4) was higher than the mean age of the predialysis group (55 ±13,1). The mean BMI (28 ±5,3), mean length (174 ±9) and mean weight (83,5 ±17,1) of all the participants were not significantly different between both groups. 23% of the study participants were smokers. There was also no significant difference in smokers or non-smokers between both groups (P= 0,918). There were no significant differences between both groups in nutritional intake.

The median CRP (6,0 [7,6]) was significantly higher in the predialysis group than in the kidney transplant group (P= 0,047). The median PTH (17,8 [36,1]) was also significantly higher in the predialysis group (P= 0,025). The median haemoglobin (7,8 [1,6]) was significantly higher in the kidney transplant group(P= 0,001). There were no significant differences in iron, ferritin, TSAT and albumin between the predialysis group and kidney transplant group. There were some missing values of the laboratory test outcomes due to errors while obtaining the blood samples or due to blood samples which were too small to analyse. There was one missing value of albumin. There were four missing values of CRP, three in the predialysis group and one in the kidney transplant group. In total there were 18 missing values of TSAT, eight in the predialysis group and ten in the kidney transplant group. The missing values of ferritin were eight in total, four in each group. There were 14 missing values of PTH, six in the predialysis and eight in the kidney transplant group. At last there were nine missing values of iron, five in the predialysis and four in the kidney transplant group.

The main primary causes of CKD among the participants in this study were ADPKD, IgA nephropathy, nephritis, FSGS and urologic causes. Of these primary kidney diseases ADPKD was the most common with 11% of the total participants in this study. The most common comorbidity in this study was hypertension with a total of 38% of all the participants in this study. In the predialysis group 45% of the participants were suffering from hypertension. There was a significant difference between the amount of participants with DM2 in the predialysis group and the kidney transplant group (P= 0,049). There were significantly more participants with DM2 in the predialysis group, respectively 38% and 12%.

The median vitamin C intake and median plasma vitamin C concentration per group are displayed in table 3. There were no significant differences between the predialysis group and the kidney transplant group. However the kidney transplant group had a slightly higher median plasma vitamin C concentration. The kidney transplant group had a slightly higher median plasma vitamin C concentration but did not reach statistical significance (p=0,098).

In table 4 the vitamin C deficiency, inadequacy and low vitamin C intake of the participants in the predialysis and kidney transplant group is presented. To examine the amount and percentage of participants with a vitamin C deficiency or inadequacy the plasma vitamin C concentration was used. In total 59% of the participants were suffering from a vitamin C inadequacy. There were significantly more participants with a vitamin C inadequacy in the predialysis group than in the kidney transplant group (P= 0,027). In the predialysis group 80% of the participants were suffering from vitamin C inadequacy and in the kidney transplant group 42% of the participants was suffering from a vitamin C inadequacy. There were also more participants with a vitamin C deficiency in the predialysis group than in the kidney transplant group. Of all the participants 17% was suffering from a vitamin C deficiency. In total there were 53% participants with a low vitamin C intake. There was a no difference between the predialysis and kidney transplant group.

Table 5 displays the vitamin C intake and plasma vitamin C concentration in man, women, smoking- and non-smoking participants, participants with a BMI of ≤25, participants with a BMI >25, participants aged ≤65 year and participants aged >65 year.

There were no significant differences in vitamin C intake in gender, smoking or non-smoking participants, BMI or age. There were no significant differences in plasma vitamin concentration between gender, smoking or non-smoking participants and age. Participants with a BMI of ≤25 had a significantly higher median plasma vitamin C concentration (38 [17,5]) than participants with a BMI of >25 (P= 0,014). This group together with women also had the highest median plasma vitamin C concentration of all the groups.

Table 7 presents the results of the list of complaints. First the group with a vitamin C deficiency, second the group with a vitamin C inadequacy and last the group without a vitamin C deficiency or inadequacy. The group with a deficiency consists of participants also included in the group with a vitamin C inadequacy.

All groups scored high on the questions “health rate” and “equally healthy”. The adequate vitamin C concentration group scored the highest on both questions.  A high score on those questions means that the participants experienced their health positive and saw them equally healthy as other persons they know. The groups with a vitamin C deficiency and inadequacy also scored high on the question “becoming sick easier” which means they think they become sick easier than other persons they know. The question “Expect health to get worse” was a question about health expectance. A high answer meant that the participant had a very low health expectance according to the participant. The group with a deficiency scored the lowest on this question and the group with an adequate vitamin C concentration scored the highest. All groups scored high in the question “excellent health” which means they experience their health as excellent. The group with a vitamin C deficiency scored the highest on “muscle pain” which means they experienced more muscle pain than the other two groups. The group with a vitamin C deficiency also scored the highest on “dry skin” which means they experiences more dry skin than the other two groups. All groups scored high on “easy bruising”, which meant that they got bruises very easily.  The complaints “chest Pain”,” Lack of appetite” “loosened teeth”, and “gingivitis” were not experienced.

There were no major differences between participants with a vitamin C deficiency, inadequacy and participants without a vitamin C inadequacy or deficiency. Complaints which could be possibly related to a vitamin C deficiency did not receive a higher score in the vitamin C deficiency group.

Table 7. Severity of complaints and health expectance of the study participants.

Vitamin C deficiency ≤10 µmol/l (n=8) Vitamin C inadequacy 10-≤35 ≤mol/l (n=15) Adequate vitamin C concentration >35 µmol/l (n=21)

Health rate1 3[2] 3[2] 4[2]

Obstruction social activities1 2[4] 4[3] 3[2]

Becoming sick easier1 4[4] 5[3] 2[4]

Equally healthy1 4[1] 4[2] 5[2]

Expect health to get worse1 1[4] 2[4] 3[4]

Health is excellent1 5[1] 4[3] 5[3]

Muscle pain 4[3] 2[2] 3[2]

Chest pain 1[0] 1[1] 1[1]

Joint pain 2[3] 2[2] 3[3]

Dry skin 4[3] 2[3] 2[3]

Itching 1[3] 2[2] 2[2]

Dizziness 1[1] 1[1] 2[3]

Shortness of breath 2[2] 1[2] 4[3]

Lack of appetite 1[3] 1[0] 1[0]

Feeling squeezed 1[3] 1([0] 1[2]

Weakness 3[3] 2[2] 3[3]

Numbness in feet/ hands 1[2] 1[1] 2[3]

Nausea/gastrointestinal disorders 1[1] 1[0] 1[2]

Poorly healing wounds 1[0] 1[1] 1[3]

Easy bruising 4[3] 3[3] 4[3]

Loosened teeth 1[0] 1[0] 1[0]

Gingivitis 1[0] 1[0] 1[1]

Fatigue 3[4] 2[3] 4[2]

Cramps 2[3] 2[4] 3[3]

Irritability 2[3] 1[1] 2[2]

All variables are stated in median and IQR unless stated otherwise.

1 score 1 is the highest and 5 is the lowest score

Haemodialysis

Finally, the results of the HD group are presented in table 7. The vitamin C intake (28,7) of this group is lower than in the predialysis or kidney transplant group. The median plasma vitamin C concentration (29) is higher than in the predialysis group and lower than in the kidney transplant group.

Table 8. Characteristics of the HD group.

HD( n=3)

Vitamin C intake (mg) 28,7

Plasma vitamin C concentration [µmol/l] 29

Energy intake (kcal) 1290

Carbohydrate intake (g) 129

Protein intake (g) 61

Fat intake (g) 61

All variables are stated in median unless stated otherwise. 

Discussion

In this cohort study 61% of the participants were suffering from a vitamin C inadequacy, most of them in the predialysis group. The plasma vitamin C concentration of the predialysis group was below the minimum reference level and the median plasma vitamin C concentration of the kidney transplant group was slightly above the minimum reference level. There was no significant difference in vitamin C plasma concentration and vitamin C intake between the predialysis and kidney transplant group. Besides the plasma vitamin C concentration, 53% of the participants had a vitamin C intake below the recommendation. The vitamin C intake of the predialysis and kidney transplant group was below the recommended minimum intake. Participants with a BMI of ≤25 had a significantly higher plasma vitamin C concentration than participants with a BMI of >25, however there was no significant difference in vitamin C intake and BMI. There was no significant difference in vitamin C intake between both groups. There was no significant difference in gender, smokers or non-smokers and age in vitamin C intake or plasma vitamin C concentration. The participants with a vitamin C inadequacy or deficiency did not score different from the other participants on the different complaints.

In our study 17% of the participants were suffering from a vitamin C deficiency (≤10 µmol/l) and 61% was suffering from a vitamin C inadequacy (10-≤35 l µmol/l). The median plasma vitamin C concentration was 23,5[29]. Due to the lack of studies about vitamin C amongst predialysis and kidney transplant patients studies amongst other CKD patients were used. Earlier studies have shown that a low vitamin C plasma concentration is common in the dialyzed population.26,27 Zhang et al. found a vitamin C deficiency in 33,45% of their participants, but also found a wide distribution in the vitamin C plasma concentration.26 Another study from Finkelstein et al. also found that 30% of their included PD patients had a vitamin C blood concentration below 30 µmol/l.27 The study of Singer et al. also found a vitamin C deficiency in 40% of the 99 dialysis and predialysis participants at the baseline.28 The loss of vitamin C due dialysis treatment could be a possible explanation for differences between the results of our study and the studies performed by Zhang et al. and Finkelstein et al. The study performed by Zhang et al. found a wide distribution in plasma vitamin C concentration among their participants which is in agreement to our findings.26

PTH was significantly lower in the kidney transplant group than in the predialysis group. The median CRP concentrations were within the reference range in both the predialysis and kidney transplant group. However, the CRP was significantly higher among participants with a vitamin C deficiency than in participants with an adequate vitamin C concentration. Albumin was lower in participants with a vitamin C deficiency, but not significantly. One study performed by Kutsal et al. found CRP concentrations above the reference range in predialysis participants.29 Another study performed by Beddhu et al. also found elevated concentrations of CRP.30 But in contrary to the study of Kutsal et al. this were participants receiving dialysis treatment.29 The CRP values found in the studies of Kutsal et al. and Beddhu et al. are in agreement with this study, although no CRP concentrations above the reference range were found in this study.

In our study no significant differences were found between participants with a vitamin C deficiency, inadequacy and adequate plasma concentrations in the complaints or health expectance. The results of a study performed by Khajehdehi et al. suggest a reduction of cramps in dialysis participants.4 Another study performed  by Levin et al. found that six of the seven healthy volunteering women suffered from mild to distinct fatigue and/or irritability.31 These results are contrary to the findings amongst the participants in our study. A randomized double-blind placebo controlled study of Singer et al. measured symptoms with the Kidney Dialysis Quality of Life-Short Form (KDOQL-SFtm), this study consisted of a placebo group and a group with participants receiving dialysis or had an estimated GFR of <20 mL/min.28 They found no significant difference in mean outcome on the questions, which is in agreement with the results of the questionnaire of complaints in our study.

The NHANES 2003-2004 is a stratified population study amongst healthy participants performed in the United States of Schleiger et al. found that the mean vitamin C intake was higher in women, non-smokers, children and older persons and participants with a healthy BMI.32 Smokers require 35 mg more vitamin C per day due to a smaller turnover of vitamin C.33,34  Overall non-smokers consumed vegetables, fruits and fruit juices more frequently than smokers.35 A third study performed by Mosdᴓl, Erens and Brunner also found that predictors of a low vitamin C plasma concentration were smoking, a low vitamin C intake and being a man.36 This study found no difference in vitamin C plasma concentration or intake between gender, age, or smoking and non-smoking participants.36 In the study performed by Schleiger et al. they found that the vitamin C intake and plasma concentration were higher in older participants, which is contrary to our findings.32 The study of Schleiger et al. consisted of 7277 participants with a more equal distribution of age then this study.32 A study performed by Wrieden et al. included 635 women and 632 men and found a higher intake in people aged ≤45.37 Only participants with a BMI ≤25 had a significantly higher plasma vitamin C concentration.37 These contrary results might be caused by the small amount of participants in our study.  

In particular we performed a prospective, observational cross-sectional study on a relatively small number of cases, this can be a possible explanation for the high standard deviations in the results in almost all variables. Because of the low number of participants the results of this study cannot be generalizable for the whole population of predialysis and transplantation patients. This study did not include a control group of healthy study participants for reference results. For this study we used a 24 hour recall method to determine the food consumption the day before the appointment of each participant. The benefits for this method include a relatively low amount of time needed to capture the food consumption of the previous day and it has a direct correlation with the vitamin C plasma concentration.34,37,38 Some participants did have a hard time to remember the food they consumed the day before, what means that it could be possible that they forgot something which makes the results of this study less reliable. There is also a possibility that participants change the eating pattern of the relevant day or overestimate the amount vitamin C containing foods. However, the 24 hour dietary recall was performed by two almost graduated students with experience in taking food histories and therefore knew to ask further if participants were not sure of their intake. It also is possible that some of the participants ate more vitamin C the day before than usually. Therefore an extended dietary history could be more precise. However an extended dietary history costs more time for the participants. All the participants were asked whether the inquired day was a conventional day in terms of food consumption for the participants. Nevertheless, the absence of specific guidelines about food consumption on the day of a plasma vitamin C measurement could still have biased the results.37 The uncertainties above can be avoided in future studies by implementation of a  follow-up design. It is possible that the plasma vitamin C concentration varies over time, due to infections and increases directly after consuming vitamin C.38 Therefore it can occur that the blood samples show no inadequacy or deficiency but the tissue levels stay deficient.34,39 Plasma vitamin C may not adequately represent tissue levels, therefore measurement of ascorbic acid in leukocytes is a better measurement of body stores but this test is not widely available. Although the test used for this study is typically used and widely available.19,39 In this study vitamin C intake and plasma concentrations were examined, this gives a much more reliable view of the vitamin C status of the participants. One of the hypotheses of this study was that a potassium-restricted diet may lead to a vitamin C deficiency or inadequacy among predialysis and kidney transplant patient. However no information about participants following a potassium-restricted diet was obtained. Another point of reflection is that the way the questions were asked, as scale questions, was sometimes experienced as difficult by the participants. However both interviewers helped the participants with answering the questions.

This study suggests that studies in the future include more participants in each of the groups to get a clearer vision of the actual vitamin C status of the participants. A second suggestion may be a follow-up design instead of a cohort study design. This way the food consumption of the participants can be inventoried over a longer period of time which reduces the uncertainties from day-to-day differences. A third suggestion might be a comparison between participants with a potassium-restricted diet and participants without a potassium-restricted diet to test this hypothesis. The final suggestion is to add a control group for reference results.

We would is a vitamin C plasma concentration measurement at least once a year. This way a vitamin C inadequacy or deficiency can be detected fast and treated. A second recommendation is even more attention to vitamin C and a healthy diet amongst CKD patients. At last the dietitian and physician should be more aware of the symptoms which accompany a vitamin C inadequacy or deficiency.

In summary, this study shows that a vitamin C deficiency was present in both groups but in particular in the predialysis group. A vitamin C inadequacy was also found in both groups. Participants with a BMI of ≤25 had a significantly higher plasma vitamin C concentration than participants with a BMI of >25. A higher CRP and lower albumin was found in participants with a vitamin C deficiency. A low vitamin C intake was also present in the predialysis group and kidney transplant group. There was no difference in complaints or health expectance between participants with a deficiency, inadequacy or adequate plasma vitamin C concentration.

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