To explore the prevalence of vitamin C deficiency, 'undetectable' vitamin C status, and scurvy features, in adult hospitalised patients with protein-energy malnutrition diagnosed using validated malnutrition screening and assessment tools commonly used in clinical practice.

This study included adult inpatients from four acute hospitals within a single Australian tertiary health service, over a 3.5-year period. A medical file review activity retrospectively determined malnutrition risk and diagnosis, via Malnutrition Screening Tool, Malnutrition Universal Screening Tool, Subjective Global Assessment and Global Leadership Initiative on Malnutrition criteria. Prevalence of vitamin C deficiency and scurvy features was examined in adult patients with plasma vitamin C levels <11.4 μmol/L and <5 μmol/L ('undetectable'), respectively.

In the final cohort (n = 364), prevalence of vitamin C deficiency was 30.2%. Malnutrition was present in 76.1% and 79.8% of patients via Subjective Global Assessment (n = 310) and Global Leadership Initiative on Malnutrition criteria (n = 342) respectively. Patients with high nutrition risk and those diagnosed with severe malnutrition had the highest prevalence of vitamin C deficiency, reported as 32.8% for malnutrition detected via Malnutrition Screening Tool (n = 244), 32.9% via Malnutrition Universal Screening Tool (n = 222), 35.8% via Subjective Global Assessment (n = 106), and 34.2% via Global Leadership Initiative on Malnutrition (n = 152). Scurvy features were associated with severe malnutrition in patients with 'undetectable' vitamin C status.

Severely malnourished adult hospital patients have a high prevalence of vitamin C deficiency, and scurvy features in those with 'undetectable' vitamin C status. Leveraging existing malnutrition screening and assessment practices may support early identification of patients with vitamin C deficiency during hospitalisation.

Assessment for vitamin C deficiency (VCD) is rarely undertaken in an acute hospital setting in high-income countries. However, with growing interest in VCD in community settings, there is emerging evidence investigating the prevalence and impact of VCD during hospitalization.

In this scoping review, the prevalence of VCD in adult hospitalized patients is explored, patient characteristics are described, and risk factors and clinical outcomes associated with VCD are identified.

A systematic scoping review was conducted in accordance with the PRISMA-ScR framework. The Ovid MEDLINE, Ovid Embase, Scopus, CINAHL Plus, Allied and Complementary Medicine Database, and the Cochrane Library databases were searched for interventional, comparative, and case-series studies that met eligibility criteria, including adult hospital inpatients in high-income countries, as defined by the Organization for Economic Co-operation and Development, that reported VCD prevalence using World Health Organization reference standards. These standards define VCD deficiency as plasma or serum vitamin C level <11.4 µmol/L, wholeblood level <17 µmol/L, or leukocytes <57 nmol/108 cells.

Twenty-three articles were included, representing 22 studies. The cumulative prevalence of VCD was 27.7% (n = 2494; 95% confidence interval [CI], 21.3-34.0). High prevalence of VCD was observed in patients with severe acute illness and poor nutritional status. Scurvy was present in 48% to 62% of patients with VCD assessed in 2 studies (n = 71). Being retired (P = 0.015) and using excessive amounts of alcohol and tobacco (P = 0.0003) were independent risk factors for VCD (n = 184). Age was not conclusively associated with VCD (n = 631). Two studies examined nutrition associations (n = 309); results were inconsistent. Clinical outcomes for VCD included increased risk of frailty (adjusted odds ratio, 4.3; 95%CI, 1.33-13.86; P = 0.015) and cognitive impairment (adjusted odds ratio, 2.93; 95%CI, 1.05-8.19, P = 0.031) (n = 160).

VCD is a nutritional challenge facing the healthcare systems of high-income countries. Research focused on early identification and treatment of patients with VCD is warranted.

Open Science Framework ( https://doi.org/10.17605/OSF.IO/AJGHX ).

Although the role of vitamins in the human body is proven, guidelines for patients with chronic kidney disease (CKD) remain unclear. This narrative review summarizes the findings of 98 studies of CKD and the effects of vitamin D, B, C, A, E, and K supplementation on patients on dialysis for CKD, with the aim of summarizing the existing guidelines. The findings are promising, showing the potential effectiveness of vitamin supplementation with, for example, vitamins B, D, or C. However, recommendations are still ambiguous, especially in the case of vitamins A and K, due to the potential toxicity associated with higher doses for patients. Continued research is needed to rigorously evaluate the effectiveness and carefully consider the potential risks of some vitamin supplementation for patients with CKD.

Growing evidence suggests that vitamin C supplementation may be an effective adjunct therapy in the management of people with diabetes. This paper critically reviews the current evidence on effects of vitamin C supplementation and its potential mechanisms in diabetes management. Evidence from meta-analyses of randomized controlled trials (RCTs) show favourable effects of vitamin C on glycaemic control and blood pressure that may be clinically meaningful, and mixed effects on blood lipids and endothelial function. However, evidence is mostly of low evidence certainty. Emerging evidence is promising for effects of vitamin C supplementation on some diabetes complications, particularly diabetic foot ulcers. However, there is a notable lack of robust and well-designed studies exploring effects of vitamin C as a single compound supplement on diabetes prevention and patient-important outcomes (i.e. prevention and amelioration of diabetes complications). RCTs are also required to investigate potential preventative or ameliorative effects of vitamin C on gestational diabetes outcomes. Oral vitamin C doses of 500-1000 mg per day are potentially effective, safe, and affordable for many individuals with diabetes. However, personalisation of supplementation regimens that consider factors such as vitamin C status, disease status, current glycaemic control, vitamin C intake, redox status, and genotype is important to optimize vitamin C's therapeutic effects safely. Finally, given a high prevalence of vitamin C deficiency in patients with complications, it is recommended that plasma vitamin C concentration be measured and monitored in the clinic setting.

Background: Hemodialysis (HD) patients are at risk of malnutrition, cardiovascular complications, and all-cause mortality due to oxidative stress and inflammation. Some studies have demonstrated that rutin attenuates oxidative stress and inflammation in CKD rats, but its effects in HD patients are unknown to date. Aim: The aim of this study was to evaluate the effect of rutin and vitamin C versus vitamin C alone on oxidative stress and inflammation in HD patients. Methods: A prospective randomized, open-label, controlled trial enrolled on hundred and five HD patients divided into three groups as follows: patients in group 1 were given a rutin/vitamin C combination (Ruta C group as the combination trade name is known as Ruta C 60 tablets), patients in group 2 were given vitamin C (1 g) (vitamin C group), and group 3 was the control group; the study period was 16 weeks. The following were assessed at baseline and at the end of the study: serum malondialdehyde (MDA), glutathione peroxidase (GPx), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), lipid profile levels, and erythrocyte sedimentation rate. Results: It was found that vitamin C significantly increased serum GPx in group 2 (p = 0.001) compared to a non-significant result in both group 1 and 3; in addition, serum MDA and TNF-α values had decreased significantly in the three groups compared to their baselines; however, a non-significant difference was seen among the studied groups at the end of the study. On the other hand, MDA levels were reduced by 50% in interventional groups compared to 28% in the control group, while the Ruta C group showed an 80% reduction in the level of TNF α compared to the 78% reduction observed in the vitamin C group, and finally, the interventional drugs showed a significant improvement in the lipid profile. Conclusion: Vitamin C supplementation alone for 16 weeks had a potential effect on the antioxidant's GPx activity. Moreover, it was reported that both vitamin C alone or the rutin/vitamin C combination (Ruta C) showed a protective role against lipid peroxidation, evidenced by the reduced levels of MDA. Finally, rutin had a favorable synergistic effect with vitamin C in reducing TG and TNF-α levels and increasing HDL-C level.

Chronic kidney disease (CKD) patients have been advised to take vitamins; however, the effects have been controversial. The individual differences in developing CKD might involve genetic variants of inflammation, including variant rs883484 located upstream of the prostaglandin-endoperoxide synthase 1 (PTGS1) gene. We aimed to identify whether the 12 dietary vitamin intake interacts with genotypes of the rs883484 on developing CKD. The population-based, cross-sectional study had 684 Japanese participants (≥40 years old). The study used a validated, brief, self-administered diet history questionnaire to estimate the intake of the dietary vitamins. CKD was defined as estimated glomerular filtration < 60 mL/min/1.73 m2. The study participants had an average age of 62.1 ± 10.8 years with 15.4% minor homozygotes of rs883484, and 114 subjects had CKD. In the fully adjusted model, the higher intake of vitamins, namely niacin (odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.57−0.96, p = 0.024), α-tocopherol (OR = 0.49, 95% CI: 0.26−0.95, p = 0.034), and vitamin C (OR = 0.97, 95% CI: 0.95−1.00, p = 0.037), was independently associated with lower CKD tendency in the minor homozygotes of rs883484. The results suggested the importance of dietary vitamin intake in the prevention of CKD in middle-aged to older-aged Japanese with minor homozygous of rs883484 gene variant.

Several studies have demonstrated a strong relation between periodontal diseases and chronic kidney disease (CKD). The main mechanisms at the base of this link are malnutrition, vitamin dysregulation, especially of B-group vitamins and of C and D vitamins, oxidative stress, metabolic acidosis and low-grade inflammation. In particular, in hemodialysis (HD) adult patients, an impairment of nutritional status has been observed, induced not only by the HD procedures themselves, but also due to numerous CKD-related comorbidities. The alteration of nutritional assessment induces systemic manifestations that have repercussions on oral health, like oral microbiota dysbiosis, slow healing of wounds related to hypovitaminosis C, and an alteration of the supporting bone structures of the oral cavity related to metabolic acidosis and vitamin D deficiency. Low-grade inflammation has been observed to characterize periodontal diseases locally and, in a systemic manner, CKD contributes to the amplification of the pathological process, bidirectionally. Therefore, CKD and oral disease patients should be managed by a multidisciplinary professional team that can evaluate the possible co-presence of these two pathological conditions, that negatively influence each other, and set up therapeutic strategies to treat them. Once these patients have been identified, they should be included in a follow-up program, characterized by periodic checks in order to manage these pathological conditions.

Vitamins are an indispensable food source and important owing to the enzyme cofactor and catalytic roles they play in the body. Fat-soluble vitamins A, D, E, K, and B12, are stored in the body and can cause problems with their excessive accumulation. Other vitamins rarely accumulate in the body because they dissolve in water and are excreted through the kidneys. Alcoholism, strict diets, insufficient parental nutrition, and gastrointestinal absorption problems may be included in the causes of vitamin deficiencies. Although clinical findings of vitamin deficiencies display different characteristics depending on the vitamins, the signs that generally occur are cutaneous pigmentation, pigmentation on mucous membranes, palmoplantar keratoderma characterized by fissures, palmar streaking, yellow streaking on the nails, nail layering, and intranail hemorrhage.

Chronic kidney disease (CKD) is characterized by manifestations and symptoms involving systemic organs and apparatus, associated with elevated cardiovascular morbidity and mortality, bone disease, and other tissue involvement. Arterial hypertension (AH), diabetes mellitus (DM), and dyslipidemia, with glomerular or congenital diseases, are the traditional risk factors recognized as the main causes of progressive kidney dysfunction evolving into uremia. Acute kidney injury (AKI) has recently been considered an additional risk factor for the worsening of CKD or the development of CKD de novo. Evidence underlies the role of systemic inflammation as a linking factor between AKI and CKD, recognizing the role of inflammation in AKI evolution to CKD. Moreover, abnormal increases in oxidative stress (OS) and inflammatory status in CKD seem to exert an important pathogenetic role, with significant involvement in the clinical management of this condition. With our revision, we want to focus on and update the inflammatory mechanisms responsible for the pathologic conditions associated with CKD, with particular attention on the development of AKI and AKI-CKD de novo, the alteration of calcium-phosphorus metabolism with bone disease and CKD-MBD syndrome, the status of malnutrition and malnutrition-inflammation complex syndrome (MICS) and protein-energy wasting (PEW), uremic sarcopenia, the status of OS, and the different inflammatory pathways, highlighting a new approach to CKD. The depth comprehension of the mechanisms underlying the development of inflammation in CKD may present new possible therapeutic approaches in CKD and hopefully improve the management of correlated morbidities and provide a reduction in associated mortality.

Vitamin C deficiency is common in chronic kidney disease (CKD) due to losses through dialysis and dietary intake below requirement. We investigated prevalence of vitamin C deficiency and impact of vitamin C treatment in deficient/insufficient patients.

A prospective cohort study in patients aged 1-18 years with CKD stages 4 and 5D collected demographic data including underlying disease, treatment, and anthropometric assessment. Vitamin C intake was assessed using 24-h dietary recall. Hemoglobin, iron status, serum vitamin C, and serum oxalate were measured at baseline and after treatment. Vitamin C (250 mg/day) was given orally for 3 months to deficient/insufficient patients.

Nineteen patients (mean age 12.00 ± 4.1 years) showed prevalence of 10.6% vitamin C insufficiency and 78.9% deficiency. There were no associations between vitamin C level and daily vitamin C intake (p = 0.64) or nutritional status (p = 0.87). Median serum vitamin C was 1.51 (0.30-1.90) mg/L. In 16 patients receiving treatment, median serum vitamin C increased from 1.30 (0.23-1.78) to 3.22 (1.77-5.96) mg/L (p = 0.008) without increasing serum oxalate (79.92 (56.6-106.84) vs. 80.47 (56.88-102.95) μmol/L, p = 0.82). However, 62.5% failed to achieve normal vitamin C levels. Ordinal regression analysis revealed patients with non-oligoanuric CKD were less likely to achieve normal vitamin C levels (β = - 3.41, p = 0.03).

We describe high prevalence of vitamin C insufficiency/deficiency among pediatric CKD patients. Vitamin C levels could not be solely predicted by nutritional status or daily intake. The treatment regimen raised serum vitamin C without increasing serum oxalate; however, it was largely insufficient to normalize levels, particularly in non-oligoanuric CKD. Graphical abstract .

Malnutrition and anorexia are common in children with chronic kidney disease (CKD) and gastrostomy tubes (GT) as well as nasogastric tubes (NGT) have been recommended to maximize nutritional support. The optimal requirement of vitamin C in children with CKD remains to be defined but oxalate is a breakdown product of vitamin C. Elevated vitamin C intake and bone oxalate were identified in two formula-fed dialyzed children with negative genetic testing for primary hyperoxaluria.

We evaluated the impact of nutritional support on serum ascorbic acid and plasma oxalate levels in 13 dialyzed infants and young children.

All patients were fed by GT or NGT since the first months of life; overall patients were receiving between 145 and 847% of the age-specific DRI for vitamin C. Mean serum ascorbic acid and plasma oxalate levels were elevated (244.7 ± 139.7 μM/L and 44.3 ± 23.1 μM/L, respectively), and values did not differ according to the degree of residual kidney function. Ascorbic acid levels did not correlate with oxalate levels (r = 0.44, p = 0.13).

Excessive vitamin C intake may contribute to oxalate accumulation in dialyzed children.

There are several observational and interventional studies regarding the advantages of sufficient serum levels of vitamin C and the evaluation of the effects of vitamin C supplementation post kidney transplantation. These studies have been put together to investigate the role of vitamin C post-kidney transplantation and make suggestions for designing future studies based on the use of vitamin C supplements or nutritional interventions among these patients.

This narrative review was done by searching in the Embase, PubMed, and SCOPUS databases.

The results are presented in several sections as follows; nutritional status, potential protective effects, safety concerns, and medications/laboratory tests interactions of vitamin C.

Kidney transplant recipients are prone to vitamin C deficiency, which is related to higher mortality based on several long-term observational studies. Vitamin C supplementation improves endothelial function and creatinine clearance. Vitamin C is considered as a safe supplement, however, side effects such as kidney stones, pro-oxidant effect, hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, impact on lymphocytic activity, acid-base disturbance, and increased sodium load following its administration have been reported. Interaction of vitamin C and cyclosporine is the most important interaction with post-renal transplant medications. Vitamin C also interferes with creatinine assay using Jaffe and enzymatic methods.

The identification of natural bioactive compounds, able to counteract the abnormal increase of oxidative stress and inflammatory status in chronic degenerative non-communicable diseases is useful for the clinical management of these conditions. We tested an oral food supplement (OFS), chemically characterized and evaluated for in vitro and in vivo activity. Vitamin C, analyzed by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD), was 0.19 mg/g in rosehip dry extract and 15.74 mg/capsule in the OFS. The identification of polyphenols was performed by HPLC-DAD; the total antioxidant capacity was assessed by Folin-Ciocalteu test. Total polyphenols were 14.73 mg/g gallic acid equivalents (GAE) for rosehip extract and 1.93 mg/g GAE for OFS. A total of 21 chronic kidney disease (CKD) patients and 10 healthy volunteers were recruited. The evaluation of routine laboratory and inflammatory parameters, erythrocyte glutathione transferase (e-GST), human oxidized serum albumin (HSAox), and assessment of body composition were performed at two different times, at baseline and after 5 weeks of OFS assumption. In the study, we highlighted a significant decrease of traditional inflammatory biomarkers (such as C-reactive protein, erythrocyte sedimentation rate, platelet to lymphocyte ratio) and other laboratory parameters like e-GST, azotaemia, and albuminuria after OFS treatment in CKD patients. Moreover, we demonstrated a lipid profile improvement in CKD patients after OFS supplementation.

Reports on vitamin C in HD patients have shown effects of vitamin C deficiency in association with scurvy symptoms. Dialyzability of water soluble vitamins is high, and substantial losses in those who are dialyzed more frequently were hypothesized. The randomized FHN Daily Trial compared the effects of in-center HD six versus three times per week. We studied baseline correlations between vitamin C and potentially associated parameters, and the effect of more frequent HD on circulating vitamin C concentrations.

We studied vitamin C levels at baseline and months, 3, 5 and 11. Patients enrolled between 2007 and 2009 into the randomized FHN Daily trial in the East Coast consortium were approached for participation. Predialysis plasma samples were processed with metaphosphoric acid and frozen at - 70 °C for measurement with HPLC. Regression models between baseline log-transformed vitamin C and hemoglobin, CRP, eKt/V, ePCR and PTH, and a linear mixed-effects model to estimate the effect size of more frequent HD on plasma vitamin C, were constructed.

We studied 44 subjects enrolled in the FHN Daily trial (50 ± 12 years, 36% female, 29% Hispanics and 64% blacks, 60% anuric). Vitamin C correlated significantly with predialysis hemoglobin (r = 0.3; P = 0.03) and PTH (r = - 0.3, P = 0.04), respectively. Vitamin C did not significantly differ at baseline (6×/week, 25.8 ± 25.9 versus 3×/week, 32.6 ± 39.4 μmol/L) and no significant treatment effect on plasma vitamin C concentrations was found [- 26.2 (95%CI -57.5 to 5.1) μmol/L at Month 4 and - 2.5 (95%CI -15.6 to 10.6) μmol/L at Month 12.

Based on data from this large randomized-controlled trial no significant effect of the intervention on circulating plasma vitamin C concentrations was found, allaying the concerns that more frequent HD would affect the concentrations of water-soluble vitamins and adversely affect patient's well-being. Correlations between vitamin C and hemoglobin and PTH support the importance of vitamin C for normal bone and mineral metabolism, and anemia management.

Oxidative stress (OS) is associated with increased morbidity and mortality in hemodialysis (HD) patients, and the consumption of fruits seems to improve OS due to their antioxidant properties. Therefore, we hypothesized that Fuji apple intake improves OS markers in HD patients due to its polyphenolic compounds without increasing serum potassium levels. This trial was a 1-group, pre- and posttest comparison between 16 patients who had been on hemodialysis for at least 3 months without any acute illness or hyperkalemia. Each volunteer consumed 2 Fuji apples (~360 g) per day for 1 week. Blood samples were collected at the baseline period and after 8 days for the measurement of total antioxidant status, ascorbic acid, catalase, glutathione peroxidase, superoxide dismutase, reduced glutathione, total oxidant status, oxidative stress index, potassium, phosphorus, uric acid, glucose, and fructosamine. For tolerance evaluation, participants were asked about their bowel habits. Apple intake increased glutathione peroxidase (P = .006) and superoxide dismutase activities (P = .006) and ascorbic acid levels (P = .002). No significant changes were observed in uric acid, potassium, phosphorus, glucose, and fructosamine levels. Additionally, there was a decrease in the catalase activity (P = .021) and in the total antioxidant status values (P = .004). However, increased total oxidant status (P = .003) and oxidative stress index (P = .033) levels were observed after apple intake. In conclusion, the intake of 2 Fuji apples per day for 1 week was well tolerated and improved antioxidant parameters in HD patients without affecting serum potassium levels.

Oxidative stress (OS) is the result of prooxidant molecules overwhelming the antioxidant defense mechanisms. Hemodialysis (HD) constitutes a state of elevated inflammation and OS, due to loss of antioxidants during dialysis and activation of white blood cells triggering production of reactive oxygen species. Dialysis vintage, dialysis methods, and type and condition of vascular access, biocompatibility of dialyzer membrane and dialysate, iron administration, and anemia all can play a role in aggravating OS, which in turn has been associated with increased morbidity and mortality. Oral or intravenous administration of antioxidants may detoxify the oxidative molecules and at least in part repair OS-mediated tissue damage. Lifestyle interventions and optimization of a highly biocompatible HD procedure might ameliorate OS development in dialysis.

Pediatric dialysis patients are at risk of nutritional illness secondary to deficiencies in water-soluble vitamins and trace elements. Unlike 25-OH vitamin D, most other vitamins and trace elements are not routinely monitored in the blood and, consequently, the detection of any deficiency may not occur until significant complications develop. Causes of vitamin and trace element deficiency in patients on maintenance dialysis patient are multifactorial, ranging from diminished nutritional intake to altered metabolism as well as dialysate-driven losses of water-soluble vitamins and select trace elements. In this review we summarize the nutritional sources of key water-soluble vitamins and trace elements with a focus on the biological roles and clinical manifestations of their respective deficiency to augment awareness of potential nutritional illness in pediatric patients receiving maintenance dialysis. The limited pediatric data on the topic of clearance of water-soluble vitamins and trace elements by individual dialysis modality are reviewed, including a brief discussion on clearance of water-soluble vitamins and trace elements with continuous renal replacement therapy.

Anemia is common and associated with adverse outcomes in children with chronic kidney disease (CKD). Many factors contribute to declining hemoglobin as CKD progresses, but impaired production of erythropoietin by failing kidneys is a central cause. Hepcidin-mediated iron restriction also contributes to anemia by downregulating both intestinal iron absorption and release of stored iron for erythropoiesis. The core components of anemia management remain erythropoiesis-stimulating agents (ESA) and iron supplementation, but despite these therapies, a substantial number of children remain anemic. Although escalating ESA dose to target higher hemoglobin has been associated with adverse outcomes in adults, no trials have investigated this association in children, and maintaining hemoglobin levels in a narrow range with conservative ESA dosing is challenging. Judicious use of iron supplementation can enhance the response to ESAs, but the iron storage markers most commonly used in clinical practice have limitations in distinguishing which patients will benefit most from additional iron. Several novel anemia therapies, including hypoxia-inducible factor stabilizers, prolyl hydroxylase inhibitors, and dialysate-delivered iron supplements, have been developed and may offer options for alternative anemia management. However, the safety and efficacy of these agents in children with CKD has yet to be assessed.

Vitamin C deficiency is difficult to diagnose on the basis of clinical presentation alone and requires plasma levels for confirmation. Reference laboratories typically specify shipment of plasma on dry ice. This requirement may complicate clinic work flow and delay vitamin C measurement. Additionally, patients with vitamin C deficiency may experience unnecessary testing and increased health-care costs, as other diagnoses are often considered first. We examined an alternative, more practical shipping method.

Plasma was collected from 17 healthy volunteers by use of heparin tubes with gel separators, and all tubes were centrifuged immediately to separate the plasma layer from the cells. Baseline vitamin C was measured in plasma obtained immediately after specimen collection. Remaining sample tubes were held in Styrofoam containers with cold packs for 30 h or 48 h, followed by vitamin C measurement. Additional samples were exposed to conditions that simulated harsher shipping conditions.

Mean plasma vitamin C was 69.6 μmol/L (SD = 21.5 μmol/L). Vitamin C losses were 5.4% at 30 h (SD = 5.55%, P < 0.05) and 7.6% at 48 h (SD = 5.56%, P < 0.05), which is slightly more than freeze-and-thaw treatment (average loss of 1.4%, SD = 6.9%, NS). The vitamin C method had an intraday variation of 1.88%. Vigorous shaking of 2 samples for 24 h resulted in a -1.9% change in 1 sample, and a +4.1% change in another sample. Exposure of the shipping container to elevated temperature (35 °C for 30 h) did not change the internal temperature of the container.

The shipping procedure uses routine sample handling, standard vacutainers, and can be replicated by health-care centers seeking to evaluate patient vitamin C status.

The achievement of erythropoiesis in hemodialysis (HD) patients is typically managed with erythropoiesis-stimulating-agents (ESA's) and intravenous iron (IV-iron). Using this treatment strategy, HD patients frequently show an elevated fraction of red blood cells (RBC) with hemoglobin (Hb) content per cell that is below the normal range, called hypochromic RBC. The low Hb content per RBC is the result of the clinical challenge of providing sufficient iron content to the bone marrow during erythropoiesis. Vitamin C supplements have been used to increase Hb levels in HD patients with refractory anemia, which supports the hypothesis that vitamin C mobilizes iron needed for Hb synthesis.

We conducted a cross-sectional survey in 149 prevalent HD patients of the percent hypochromic RBC, defined as RBC with Hb < 300 ng/uL of packed RBC, in relation to plasma vitamin C levels. We also measured high-sensitivity CRP, (hs-CRP), iron, and ferritin levels. and calculated ESA dose.

High plasma levels of vitamin C were negatively associated with hypochromic RBC (P < 0.003), and high ESA doses were positively associated (P < 0.001). There was no significant association of hs-CRP with percent hypochromic RBC.

This finding supports the hypothesis that vitamin C mobilizes iron stores, improves iron delivery to the bone marrow, and increase the fraction of RBC with normal Hb content. Further research is warranted on development of protocols for safe and effective use of supplemental vitamin C for management of renal anemia.

Hemodiafiltration with on-line endogenous reinfusion (HFR) is an extracorporeal dialytic method that combines diffusion, convection and adsorption. HFR-Supra (HFR-S) is a second-generation system with increased convective permeability and adsorption capability. Previous studies suggested that HFR reduces oxidative stress compared to standard haemodialysis. The principal aim of the present study was to compare antioxidant vitamins behavior and oxidative status of hemodialysis patients treated with HFR and HFR-S.

The study was designed as a multicenter, randomized, crossover trial. Forty-one patients were recruited from 19 dialysis centers and after a 4-month washout stabilization period in on-line hemodiafiltration (ol-HDF), each patient was randomized to a sequence of treatments (HFR-S followed by HFR or viceversa) with each treatment applied over 6 months. Plasma levels of Advanced Oxidation Protein Products, Total Antioxidant Status, vitamins C, A and E and their ligands (Retinol Binding Protein and total lipids) were measured at baseline and at the end of each treatment period.

Results show that the higher convective permeability of HFR-S with respect to HFR did not produce additional beneficial effects on the patients' oxidative status, a slight decrease of both Vitamin A and Retinol Binding Protein being the only difference registered in the long-term. However, as compared to ol-HDF, both the re-infusive techniques allowed to reduce the intradialytic loss of Vitamin C and, in the long-term, improve the patients' oxidative status and increase Retinol Binding Protein plasma values. No significant differences were found between the Vitamin C concentration of pre- and post cartridge UF neither in HFR-S nor in HFR showing that the sorbent resin does not adsorb Vitamin C.

HFR-S and HFR are almost equivalent in term of impact on antioxidant vitamins and oxidative status of hemodialysis patients. Nonetheless, as compared to ol-HDF, both treatments produced a sensible sparing of Vitamin C and may represent a new approach for reducing oxidative stress and related complications in dialysis patients. Long-term effects of re-infusive treatments on patients' cardiovascular morbidity and mortality need to be evaluated.

ClinicalTrials.gov Identifier NCT01492491 , retrospectively registered in 10 December 2011.

Patients with chronic kidney disease (CKD) or end-stage renal disease are at risk for vitamin C deficiency and scurvy due to diet restriction, increased urinary loss of the water-soluble vitamin C with diuretics, and in case of patients who are on dialysis, through dialysates. The condition may be overlooked as the clinical manifestation of scurvy may be subtle, and some presentations may mimic clinical signs in CKD. We reported a case of scurvy presenting with gingival bleeding and blood dialysate in a 6-year-old girl with end-stage renal disease who was on continuous ambulatory peritoneal dialysis. Physical examination showed gingival hyperplasia and bleeding, and the pathognomonic bleeding of perifollicular hemorrhage. The typical radiographic changes were present. The clinical signs and symptoms resolved after ascorbic acid treatment. This case underscores the importance of awareness of the increased risk for vitamin C deficiency in patients with CKD and receiving dialysis.

In this work, we develop an impulsive mathematical model of Vitamin C (ascorbic acid) metabolism in healthy subjects for daily intake over a long period of time. The model includes the dynamics of ascorbic acid plasma concentration, the ascorbic acid absorption in the intestines and a novel approach to quantify the glomerular excretion of ascorbic acid. We investigate qualitative and quantitative dynamics. We show the existence and uniqueness of the global asymptotic stability of the periodic solution. We also perform a numerical simulation for the entire time period based on published data reporting parameters reflecting ascorbic acid metabolism at different oral doses of ascorbic acid.