ascorbic-acid and Kidney-Failure--Chronic

Increasingly, chronic kidney disease (CKD) is becoming an inevitable consequence of obesity, metabolic syndrome, and diabetes. As the disease progresses, and through dialysis, the need for and loss of water-soluble vitamins both increase. This review article looks at the benefits and possible risks of supplementing these vitamins with the treatment of CKD.. Data in the PubMed and Embase databases were analyzed. The keywords "chronic kidney disease", in various combinations, are associated with thiamin, riboflavin, pyridoxine, pantothenic acid, folates, niacin, cobalamin, and vitamin C. This review focuses on the possible use of water-soluble vitamin supplementation to improve pharmacological responses and the overall clinical condition of patients.. The mechanism of supportive supplementation is based on reducing oxidative stress, covering the increased demand and losses resulting from the treatment method. In the initial period of failure (G2-G3a), it does not require intervention, but later, especially in the case of inadequate nutrition, the inclusion of supplementation with folate and cobalamin may bring benefits. Such supplementation seems to be a necessity in patients with stage G4 or G5 (uremia). Conversely, the inclusion of additional B6 supplementation to reduce CV risk may be considered. At stage 3b and beyond (stages 4-5), the inclusion of niacin at a dose of 400-1000 mg, depending on the patient's tolerance, is required to lower the phosphate level. The inclusion of supplementation with thiamine and other water-soluble vitamins, especially in peritoneal dialysis and hemodialysis patients, is necessary for reducing dialysis losses. Allowing hemodialysis patients to take low doses of oral vitamin C effectively reduces erythropoietin dose requirements and improves anemia in functional iron-deficient patients. However, it should be considered that doses of B vitamins that are several times higher than the recommended dietary allowance of consumption may exacerbate left ventricular diastolic dysfunction in CKD patients.. Taking into account the research conducted so far, it seems that the use of vitamin supplementation in CKD patients may have a positive impact on the treatment process and maintaining a disease-free condition.

Topics: Ascorbic Acid; Dietary Supplements; Folic Acid; Humans; Kidney Failure, Chronic; Niacin; Renal Dialysis; Renal Insufficiency, Chronic; Thiamine; Vitamin B 12; Vitamin B Complex; Water

Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD. Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD. Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, with increased prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end-stage renal disease. This is an update of a review first published in 2017.. To assess the effectiveness of any intervention for preventing or reducing kidney complications or chronic kidney disease in people with sickle cell disease. Possible interventions include red blood cell transfusions, hydroxyurea, and angiotensin-converting enzyme inhibitors (ACEIs), either alone or in combination.. We searched for relevant trials in the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, CENTRAL, MEDLINE, Embase, seven other databases, and two other trials registers.. Randomised controlled trials (RCTs) comparing interventions to prevent or reduce kidney complications or CKD in people with SCD. We applied no restrictions related to outcomes examined, language, or publication status.. Two review authors independently assessed trial eligibility, extracted data, assessed the risk of bias, and assessed the certainty of the evidence (GRADE).. We are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations. We are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria. We are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria. No RCTs assessed red blood cell transfusions or any combined interventions to prevent or reduce kidney complications. Due to lack of evidence, we cannot comment on the management of children aged over 18 months or adults with any known genotype of SCD. We have identified a lack of adequately designed and powered studies, although we found four ongoing trials since the last version of this review. Only one ongoing trial addresses renal function as a primary outcome in the short term, but such interventions have long-term effects. Trials of hydroxyurea, ACEIs or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction of kidney complications in people with SCD.

Topics: Acute Chest Syndrome; Adolescent; Adult; Anemia, Sickle Cell; Angiotensin-Converting Enzyme Inhibitors; Antisickling Agents; Ascorbic Acid; Captopril; Child; Creatinine; Humans; Hydroxyurea; Kidney Failure, Chronic; Lisinopril; Proteinuria

Hemodialysis (HD) patients often have inadequate nutrition, especially with respect to ascorbic acid (AA). It is reported that every HD session may cause a 50%- 75% decrease in plasma AA levels. Some studies have shown that supplementation of AA can change the outcome of chronic kidney disease-mineral bone disorders (CKD-MBD), but the effect of AA on HD patients with CKD-MBD remains controversial. Consequently, we decided to perform a meta-analysis to evaluate the efficacy of AA supplementation in CKD-MBD patients requiring dialysis.. A search was conducted using Pubmed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and VIP information database up to April 2018 for all English and Chinese language publications. The main indicators of our study were changes in serum phosphate (P), calcium (Ca) and parathyroid hormone (PTH) levels after AA treatment. The efficacy of AA was evaluated by weighted mean difference (WMD) and confidence intervals (CI). Cardiovascular events, mortality and adverse events reported during the experiment were also noted.. In total, 371 patients in six studies were involved in this meta-analysis. Compared to placebo, AA treatment had no positive effect on serum P (353 patients; WMD = -0.05; 95% CI, -0.3 to 0.2; I2 = 28%) or PTH levels (275 patients; WMD = -17.04; 95%CI, -63.79 to 29.72; I2 = 75%). The pooled mean difference of the change of Ca levels from baseline was higher in the AA therapy group versus placebo (353 patients; WMD = 0.15; 95% CI, 0.01 to 0.3; I2 = 0%). No side effects were observed.. Our systematic review and meta-analysis does not support prescription of AA to HD patients with CKD-MBD. AA had no positive effect on CKD-MBD patients as it couldn't influence the serum P or PTH levels but did raise serum Ca levels in the short-term.

Topics: Ascorbic Acid; Bone Diseases; Calcium; Humans; Kidney Failure, Chronic; Minerals; Parathyroid Hormone; Phosphorus; Randomized Controlled Trials as Topic; Renal Dialysis

Patients on dialysis often develop anemia, which is accompanied by the development of substantial iron stores after administration of intravenous iron. This can be remedied in some instances with administration of supplemental vitamin C, either intravenously or orally. This is because of the mobilization of stored iron, which results in correction of anemia and in improvement of iron-indices of red cells and reticulocytes. The short red cell survival often seen in patients on dialysis creates a situation in which very large amounts of iron are needed to be supplied for new erythropoiesis, and vitamin C therefore contributes to necessary iron delivery. The safety of this therapy needs careful study so as to determine vitamin C dosage that is effective and also avoids complications of oxalosis.

Topics: Anemia; Ascorbic Acid; Dietary Supplements; Humans; Kidney Failure, Chronic; Renal Dialysis; Vitamins

To determine the impact of adjuvant ascorbic acid therapy on erythropoietin-hyporesponsive, anemic patients undergoing hemodialysis.. The online databases of PubMed, Cochrane library, IPA, CINAHL, EMBASE, clinicaltrial.gov, WHO trial registry and PyschINFO were used.. Studies comparing ascorbic acid to a control, with participants receiving erythropoietin and hemodialysis, and reported outcomes for hemoglobin or transferring saturation.. Two independent researchers reviewed titles and abstracts to determine relevance and extracted study design, dose, duration, baseline values, and outcomes.. Five studies met all the criteria and were used for final analysis. The calculated weighted mean difference between hemoglobin in the ascorbic acid group versus the control group was 0.96 g/dL (95% CI, 0.78 to 1.14). The calculated weighted mean difference between transferrin saturation in the ascorbic acid treatment group versus the control was 8.26% (95% CI, 6.59 to 9.94).. Adjuvant ascorbic acid significantly raises hemoglobin levels in patients with erythropoietin hyporesponsiveness undergoing hemodialysis. The significant rise in transferrin saturation indicates that this positive effect on erythropoietin response may be due to increased iron utilization.

Topics: Adult; Anemia; Antioxidants; Ascorbic Acid; Erythropoietin; Female; Hemoglobins; Humans; Injections, Intravenous; Iron; Iron Overload; Kidney Failure, Chronic; Male; Middle Aged; Randomized Controlled Trials as Topic; Renal Dialysis

Ascorbic acid is believed to improve anemia in patients with end-stage renal disease, but its overall effectiveness is unclear.. Systematic review and meta-analysis.. Adult hemodialysis patients.. Randomized clinical trials of ascorbic acid use in addition to standard anemia management.. Ascorbic acid.. Weighted mean difference (WMD) for change in hemoglobin level, recombinant human erythropoietin (rHuEPO) dose, transferrin saturation and ferritin level and adverse events.. Of 157 potentially relevant studies, 6 studies (n = 326 patients) met the inclusion criteria. Combining the 3 randomized clinical trials involving patients with baseline hemoglobin levels <11 g/dL, change in hemoglobin level was greater for ascorbic acid use compared with standard care (WMD, 0.9 g/dL; 95% CI, 0.5-1.2 g/dL). Compared with standard care, ascorbic acid use also was associated with a statistically significant decrease in rHuEPO dose (WMD, -17.1 U/kg/wk; 95% CI, -26.0 to -8.2 U/kg/wk) and improvement in transferrin saturation (WMD, 7.9%; 95% CI, 5.2-10.5%), with no change in ferritin concentration. Adverse events had questionable relevance to ascorbic acid use; no study reported oxalate levels or occurrence of oxalosis.. Small number of studies, heterogeneity between study populations, and study durations were short. Adverse events were poorly reported.. Although the studies are limited by small numbers of subjects, short durations of follow-up, and variable quality, these results suggest that compared with standard care, ascorbic acid use may result in an increase in hemoglobin concentration and transferrin saturation and decrease in rHuEPO requirements. Longer term studies are required to confirm these results, provide information about adverse events, and determine whether these changes translate into improved patient outcomes and cost-effectiveness.

Topics: Adult; Anemia; Ascorbic Acid; Dose-Response Relationship, Drug; Hemoglobins; Humans; Kidney Failure, Chronic; Middle Aged; Renal Dialysis; Treatment Outcome

It has been widely established that patients with end-stage renal disease undergoing chronic haemodialysis therapy exhibit low endogenous levels of L-carnitine and elevated acylcarnitine levels; however, the clinical implication of this altered carnitine profile is not as clear. It has been suggested that these disturbances in carnitine homeostasis may be associated with a number of clinical problems common in this patient population, including erythropoietin-resistant anaemia, cardiac dysfunction, and dialytic complications such as hypotension, cramps and fatigue. In January 2003, the Centers for Medicare and Medicaid Services (USA) implemented coverage of intravenous L-carnitine for the treatment of erythropoietin-resistant anaemia and/or intradialytic hypotension in patients with low endogenous L-carnitine concentrations. It has been estimated that in the period of 1998-2003, 3.8-7.2% of all haemodialysis patients in the USA received at least one dose of L-carnitine, with 2.7-5.2% of patients receiving at least 3 months of supplementation for one or both of these conditions. The use of L-carnitine within Australia is virtually non-existent, which leads us to the question: Are Australian haemodialysis patients missing out? This review examines the previous research associated with L-carnitine administration to chronic dialysis patients for the treatment of anaemia, cardiac dysfunction, dyslipidaemia and/or dialytic symptoms, and discusses whether supplementation is warranted within the Australian setting.

Topics: Anemia; Ascorbic Acid; Carnitine; Follow-Up Studies; Humans; Kidney Failure, Chronic; Prevalence; Renal Dialysis; South Australia; Treatment Outcome; Vitamin B Complex; Vitamins; Western Australia

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Dietary Supplements; Erythropoiesis; Humans; Kidney Failure, Chronic; Prognosis; Renal Replacement Therapy; Vitamins

Anemia prevention for hemodialysis relies primarily on supplemental erythropoietin (EPO) and intravenous iron (IV-iron). The doses of EPO utilized are somewhat higher than normal endogenous rates of EPO production in healthy subjects, and the amount of IV-iron used to boost red blood cell (RBC) production may be greater than the amounts used for erythropoiesis. EPO and IV-iron might be used more efficiently if two fundamental problems were solved in the management of dialysis patients: better vitamin C status, and avoidance of chronic inflammation. The low levels of plasma vitamin C commonly observed in dialysis patients restrict mobilization of stored iron from the reticuloendothelial system (RES), and inflammation has a very similar effect. The impact of low vitamin C levels and concurrent inflammation causes a large amount of iron to be stored, with relatively inefficient utilization for erythropoiesis. Vitamin C intake for dialysis patients is often restricted because of avoidance of vitamin C-rich foods, and because of concerns about oxalosis. Inflammation is a chronic feature of renal disease, which is compounded by infections from use of catheters. Research strategies to improve vitamin C status and to decrease inflammation would lead to better utilization of iron and EPO, and could have parallel benefits for the long-term health of patients on hemodialysis.

Topics: Anemia; Ascorbic Acid; Ascorbic Acid Deficiency; Hematopoiesis; Humans; Kidney Failure, Chronic; Renal Dialysis

Anemia is a common complication of chronic kidney disease, particularly in patients who are on dialysis. The use of recombinant human erythropoietin has led to the eradication of severe anemia in the dialysis population. Correction of anemia in these patients has been associated with better quality of life and clinical outcomes. Some hemodialysis patients have anemia that either is relatively refractory to epoetin therapy or requires very high doses of epoetin (i.e., hyporesponsiveness), despite having adequate iron stores, and are thus unable to achieve or maintain target hemoglobin levels. Several pharmacologic agents have been studied for effects on improving response to epoetin, either to counter hyporesponsiveness or simply to reduce epoetin use for purely economic reasons. This review examines the available literature regarding the efficacy of these potential pharmacologic adjuvants to epoetin in the treatment of anemia in patients on maintenance hemodialysis, with special emphasis on androgens, vitamin C (ascorbic acid), and L-carnitine. A review of published guidelines and recommendations for use of these agents in hemodialysis patients is provided.

Topics: Adjuvants, Pharmaceutic; Androgens; Anemia, Iron-Deficiency; Antioxidants; Ascorbic Acid; Carnitine; Erythropoietin; Female; Humans; Iron; Kidney Failure, Chronic; Male; Practice Guidelines as Topic; Renal Dialysis; Treatment Outcome

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Ascorbic Acid; Drug Design; Erythropoietin; Hematinics; Humans; Iron; Japan; Kidney Failure, Chronic; Practice Guidelines as Topic; Prognosis; Quality of Life; Recombinant Proteins; Renal Dialysis

Topics: Anemia, Iron-Deficiency; Ascorbic Acid; Biomarkers; Drug Resistance; Erythropoietin; Ferritins; Humans; Iron; Kidney Failure, Chronic; Quality of Life; Recombinant Proteins; Renal Dialysis; Transferrin

Renal failure is accompanied by oxidative stress, which is caused by enhanced production of reactive oxygen species and impaired antioxidant defense. The suggested therapeutical interventions aimed at reducing oxidative stress in chronic renal failure patients are as follows: 1) the use of biocompatible membranes, ultrapure dialysate, and removal of endogenous foci of infection; 2) haemolipodialysis, and electrolysed reduced water for dialysate preparation; 3) administration of antioxidants (alpha-tocopherol, ascorbic acid, N-acetylcysteine, reduced glutathione); 4) substances possibly affecting oxidative stress indirectly (erythropoietin, sodium selenite). As currently available data have, as yet, provided rather limited evidence for the clinical benefit of antioxidant interventions, at present it is untimely to give practical recommendations with regard to antioxidant treatment of patients with renal failure.

Topics: Antioxidants; Ascorbic Acid; Humans; Kidney Failure, Chronic; Oxidative Stress; Renal Dialysis; Tocopherols; Treatment Outcome; Vitamin E

Increments of oxidative stress have been addressed as one potential cause for the accelerated atherosclerosis of chronic kidney disease patients. Ascorbate represents one of the most prominent antioxidants both in plasma as well as intracellulary, exerting beneficial effects by an inhibition of lipid peroxidation and by reducing endothelial dysfunction. However, in the presence of transition metals like iron, ascorbate may give rise to an increased generation of oxidants, and ascorbylation may impose additional carbonyl stress to uremic patients. Unsupplemented dialysis patients have reportedly lower plasma levels of ascorbate in comparison to healthy controls, mostly due to a loss into the dialysate or, in case of not dialyzed patients, increased urinary losses. Currently, 60 mg of ascorbate are recommended for chronic kidney disease patients, and 1-1.5 g of oral ascorbate/week in case of suspected subclinical ascorbate deficiency or 300 mg parenteral ascorbate/dialysis session, respectively. Ascorbate's role in modifying arterial blood pressure remains unclear, but anemic patients with functional iron deficiency might benefit from short-term, moderately dosed ascorbate supplements.

Topics: Anemia, Iron-Deficiency; Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Endothelium, Vascular; Humans; Iron; Kidney Failure, Chronic; Renal Dialysis

Provision of sufficient available iron is a prerequisite to ensure the optimal response to recombinant human erythropoietin (rHuEpo). Functional iron deficiency (a state when iron supply is reduced to meet the demands for increased erythropoiesis) is the common cause of rHuEpo hyporesponsiveness in dialysis patients who have normal iron status, even when they are iron-overloaded. Iron supplementation is not justified for this hyporesponsiveness in patients with iron overload due to the potential hazards of iron overload aggravated by intravenous iron therapy. Furthermore, in vivo studies indicated that the promising effect of intravenous iron medication to overcome iron-deficient erythropoiesis is not observed in iron-overloaded haemodialysis (HD) patients. Ascorbic acid, a water-soluble antioxidant as well as a reducing agent, has a number of associations with iron metabolism. Recent research highlights that ascorbic acid can potentiate the mobilization of iron from inert tissue stores and facilitates the incorporation of iron into protoporphyrin in iron-overloaded HD patients being treated with rHuEpo. Interest has turned towards the use of ascorbic acid as an adjuvant therapy in this field. This review focuses on the improvement of rHuEpo response by administration of ascorbic acid and discusses its clinical implications and potential issues for nephrologists.

Topics: Ascorbic Acid; Drug Synergism; Erythropoietin; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Recombinant Proteins

Adjuvant therapy may allow patients being treated with epoetin to derive greater clinical benefits. Iron supplementation is currently the most widely used form of adjuvant therapy; intravenous (i.v.) iron is required by the majority of haemodialysis patients receiving epoetin. Measurement of hypochromic red blood cells is the most direct way of assessing iron supply to the bone marrow. During the correction phase, a dose of i.v. iron equivalent to 50 mg/day is recommended, with the total dose not exceeding 3 g. When subclinical vitamin C deficiency is suspected, ascorbic acid may be given orally (1-1.5 g/week) or i.v. (300 mg three times weekly at the end of dialysis). The active vitamin D metabolites alfacalcidol and calcitriol may, under some circumstances, improve anaemia and reduce epoetin dosage requirements. Vitamin B6 requirements are increased during epoetin therapy, and supplementation at a dose of 100-150 mg/week is recommended. Supplementation of vitamin B12 is optional. Folic acid is supplemented routinely in haemodialysis patients, though evidence that it increases the efficacy of epoetin is limited. Low doses (2-3 mg/week) should normally be sufficient to maintain optimal folic acid stores in epoetin-treated patients, although higher doses are necessary for patients with hyperhomocysteinaemia. L-Carnitine supplementation may be appropriate in some patients with anaemia of chronic renal failure (CRF) unresponsive to, or requiring large doses of, epoetin. Androgens potentially could reduce epoetin costs in countries with limited resources, but should only be used in men older than 50 years with a remnant kidney. Recent animal studies indicate that the combination of epoetin and insulin-like growth factor 1 might be beneficial in CRF patients. High doses of angiotensin-converting enzyme (ACE) inhibitors should be reserved for dialysis patients who have hypertension that cannot be controlled by other agents, or who require an ACE inhibitor for treatment of heart failure.

Topics: Androgens; Anemia; Angiotensin-Converting Enzyme Inhibitors; Ascorbic Acid; Carnitine; Cytokines; Erythropoietin; Humans; Iron; Kidney Failure, Chronic; Pyridoxine; Vitamin D

Optimizing the use of recombinant human erythropoietin (r-HuEPO) involves choosing an appropriate dose regimen and target haemoglobin level, addressing factors that inhibit response, and considering appropriate adjuvant therapy. Subcutaneous administration of r-HuEPO two or three times weekly is optimal for most patients. Early detection and treatment of iron deficiency is mandatory. Measurement of the percentage of hypochromic red blood cells is a reliable marker of functional iron deficiency, and the treatment of choice is intravenous iron. Other factors that can affect the response to r-HuEPO include blood loss (sometimes occult), infection, inflammation, hyperparathyroidism with marrow fibrosis, aluminium toxicity, vitamin B12/folate deficiency, haemolysis, bone marrow disorders, haemoglobinopathies, under-dialysis and possibly angiotensin-converting enzyme inhibitors. These factors should be identified and corrected where possible. Ascorbic acid, vitamin D, folic acid, carnitine, other cytokines and growth factors have all been shown to augment the response to r-HuEPO in some patients. Further research is required before any of these adjuvant therapies can be incorporated into routine clinical practice. With regard to target haemoglobin value, the current practice is to aim for a level of 10-12 g/dl, but it may be argued that a higher target would achieve greater benefits in terms of physical performance, quality of life, and possibly cardiac morbidity and mortality. International multicentre trials are currently in progress to address this issue, as are studies on other substances that may be able to stimulate erythropoiesis.

Topics: Anemia; Ascorbic Acid; Carnitine; Clinical Trials as Topic; Cytokines; Drug Administration Schedule; Erythropoietin; Folic Acid; Growth Substances; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Iron; Iron Deficiencies; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Vitamin D

Renal failure results in the retention of metabolites which may arbitrarily be grouped according to their molecular weight: low (< 300 daltons molecular weight), middle (300-15,000 daltons), and high (> 15,000 daltons). Opinion in respect to the relative importance of these groups varies. Initially it was thought that small molecules were important. In the mid-1970s, investigators identified the possible pathophysiological role of middle molecules. However, since positive identification of such molecules was difficult, opinion has shifted back in favor of small molecules, and little attention, with the exception of beta 2 microglobulin, has been paid to middle molecules and their removal by hemodialysis and related therapies. In this review current knowledge regarding middle molecules identified as uremic toxins and their removal by hemodialysis and associated therapies are discussed.

Topics: Ascorbic Acid; Atrial Natriuretic Factor; beta 2-Microglobulin; Calcitonin Gene-Related Peptide; Chloramines; Endorphins; Glycosylation; Humans; Kidney Failure, Chronic; Molecular Weight; Parathyroid Hormone; Peptides; Renal Dialysis; Toxins, Biological

Topics: Ascorbic Acid; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Metabolism, Inborn Errors; Oxalates; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Thiamine Deficiency; Vitamin B 6 Deficiency

Administration of intravenous vitamin C in hemodialysis patients can reduce their ferritin levels. Nevertheless, little research has been carried out in this regard. Hence, this study aimed to determine the effect of intravenous vitamin C on ferritin levels in a group of hemodialysis patients.. The study population included 32 patients with chronic renal failure undergoing hemodialysis who had been referred to Qazvin Hospital. These patients had functional iron deficiency (IDA) and high levels of serum ferritin. Patients were randomly allocated into intervention group A (n = 16) and control group B (n = 16). Group A was given intravenous ascorbic acid, while group B was given the same amount of distilled water as a placebo three times a week after each dialysis session for three months along with erythropoietin. Laboratory parameters were assessed at the beginning and the end in an interval of three months.. In patients who received vitamin C injections, the mean ferritin level decreased at the end of the study (P < .05). But vitamin C intake did not affect BUN, creatinine, sodium, potassium, TIBC, hemoglobin, platelets count, and the length and number of dialysis sessions.. Results of our study showed that vitamin C can reduce serum ferritin levels in hemodialysis patients. Therefore, it can be used as an adjunct in the treatment of anemia in patients.  DOI: 10.52547/ijkd.6531.

Topics: Anemia; Ascorbic Acid; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Vitamins

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.

Topics: Adult; Ascorbic Acid; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Treatment Outcome

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.

Topics: Adult; Advanced Oxidation Protein Products; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Cross-Over Studies; Female; Hemodiafiltration; Humans; Kidney Failure, Chronic; Lipids; Male; Middle Aged; Oxidative Stress; Prospective Studies; Retinol-Binding Proteins, Plasma; Vitamin A; Vitamin E; Young Adult

People with kidney failure are often deficient in zinc and selenium, but little is known about the optimal way to correct such deficiency.. We did a double-blind randomized trial evaluating the effects of zinc (Zn), selenium (Se) and vitamin E added to the standard oral renal vitamin supplement (B and C vitamins) among hemodialysis patients in Alberta, Canada. We evaluated the effect of two daily doses of the new supplement (medium dose: 50 mg Zn, 75 mcg Se, 250 IU vitamin E; low dose: 25 mg Zn, 50 mcg Se, 250 IU vitamin E) compared to the standard supplement on blood concentrations of Se and Zn at 90 days (primary outcome) and 180 days (secondary outcome) as well as safety outcomes.. We enrolled 150 participants. The proportion of participants with low zinc status (blood level <815 ug/L) did not differ between the control group and the two intervention groups at 90 days (control 23.9% vs combined intervention groups 23.9%, P > 0.99) or 180 days (18.6% vs 28.2%, P = 0.24). The proportion with low selenium status (blood level <121 ug/L) was similar for controls and the combined intervention groups at 90 days (32.6 vs 19.6%, P = 0.09) and 180 days (34.9% vs 23.5%, P = 0.17). There were no significant differences in the risk of adverse events between the groups.. Supplementation with low or medium doses of zinc and selenium did not correct low zinc or selenium status in hemodialysis patients. Future studies should consider higher doses of zinc (≥75 mg/d) and selenium (≥100 mcg/d) with the standard supplement.. Registered with ClinicalTrials.gov (NCT01473914).

Topics: Aged; Alberta; Ascorbic Acid; Avitaminosis; Deficiency Diseases; Dietary Supplements; Double-Blind Method; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Selenium; Trace Elements; Treatment Outcome; Vitamin B Complex; Vitamin E; Vitamins; Zinc

Clinical studies of recent years have shown that hyperuricemia is associated with poor outcomes such as cardiovascular mortality and dialysis inadequacy in patients undergoing hemodialysis. Our study investigated the effect of vitamin C supplementation on serum uric acid levels in hemodialysis patients.. This randomized placebo-controlled trial was conducted on 172 hemodialysis patients. They were randomly divided into the intervention group, to receive 250 mg of vitamin C, three times per week, for 8 weeks, and control groups 1 and 2, to receive placebo injection (saline) and no intervention, respectively. Serum levels of uric acid and creatinine were measured at the start of the study and also after 8 weeks.. The mean of serum levels of uric acid was 6.02 ± 1.08 mg/dL (reference range, 2.6 mg/dL to 6 mg/dL). Nearly, half of the patients (46.7%) had a serum level of uric acid greater than 6 mg/dL. The median baseline serum levels of uric acid were 6.2 mg/dL, 5.9 mg/dL, and 6 mg/dL in the intervention, control 1, and control 2 groups, respectively (P = .19). After 2 months, median levels reduced significantly in the vitamin C group to 5.8 mg/dL as compared to 6.4 mg/dL and 6.3 mg/dL in control groups (P = .02). The mean serum creatinine level had no significant changes during the study.. Our results demonstrated the existence of a significant negative relationship between vitamin C and serum uric acid levels. Detailed investigations with larger sample sizes and longer-term use of vitamin C are recommended.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Creatinine; Dietary Supplements; Female; Humans; Hyperuricemia; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Treatment Outcome; Uric Acid; Vitamins; Young Adult

We evaluate the effect of the protoconized anemia therapy on adverse events using the Hb and ferritin levels of individual patients undergoing maintenance hemodialysis (MHD).. Design: A randomized, parallel group, multi-center study.. Two hundred sixty-six MHD patients. Intervention group: The doses of erythropoietin, iron, and vitamin C were adjusted every month based on the ferritin and hemoglobin (Hb) levels according to the protocol. Non-intervention group: The attending physician determined the doses of erythropoietin and iron.. The maintenance rate of target Hb and ferritin levels were significantly higher in the Intervention group than in the Non-intervention group. The frequency of hospitalization was significantly lower for patients with a higher maintenance rate of target Hb levels than for those with a lower maintenance rate.. Using an anemia treatment protocol according to the individual Hb and ferritin levels of hemodialysis patients might stabilize the Hb and ferritin levels, which in turn could contribute to the lower frequency of adverse events in MHD patients.

Topics: Adult; Aged; Anemia; Ascorbic Acid; Biomarkers; Drug Dosage Calculations; Drug Monitoring; Drug Therapy, Combination; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Hospitalization; Humans; Iron; Japan; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Renal Dialysis; Time Factors; Treatment Outcome

Some studies have shown that antioxidant ascorbic acid has renal protective effects, but the beneficial effects of contrast-induced nephropathy prevention remain to be clearly shown. Therefore, we aimed to determine whether ascorbic acid pretreatment reduces the risk of contrast-induced nephropathy in a high-risk population of patients with renal insufficiency undergoing coronary angiography.. We conducted a prospective, randomized, controlled trial, involving 156 consecutive patients with chronic renal insufficiency (calculated estimated glomerular filtration rate<60 mL/min/1.73 m(2) and/or serum creatinine≥1.1 mg/dL) undergoing coronary angiography. Patients were randomized to ascorbic acid (n=74, 3 g intravenous injection before the procedure and oral 1 g per day for 2 days after the procedure, ascorbic acid group) or sodium chloride alone (n=82, control group). All patients received pre-and postprocedure hydration.. There was no difference between the ascorbic acid group and control group in mean peak increase in serum creatinine measured within 48 hours after coronary angiography, the primary study end point (0.012±0.146 vs 0.022±0.212 mg/dL respectively, p=0.216). The incidence of contrast-induced nephropathy, a secondary end point defined as increase of either≥25% or ≥0.5 mg/dL in serum creatinine, was 5.4% in ascorbic acid-treated patients (4/74) and 6.3% in control group patients (6/82), a nonsignificant difference (p=0.690). There were also no differences between the 2 groups in the inhospital clinical outcomes or length of hospital stay.. Ascorbic acid pretreatment for short-term at high dose do not prevent renal function deterioration after administration of contrast medium in patients with baseline renal insufficiency undergoing coronary angiography.

Topics: Acute Kidney Injury; Administration, Oral; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Cardiac Catheterization; Contrast Media; Coronary Angiography; Female; Fluid Therapy; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Premedication; Prospective Studies; Risk Factors; Treatment Failure

Reticuloendothelial blockade in hemodialysis patients prevents optimal intravenous (IV) iron utilization. Vitamin C has emerged as a potential therapy to improve anemia treatment by enhancing iron mobilization. However, Vitamin C can act as a pro-oxidant in the presence of iron. This was a prospective, open-label, crossover study. Thirteen patients with end-stage renal disease on hemodialysis and four healthy controls were assigned to receive 100 mg of IV iron sucrose (IS) or 100 mg of IV IS co-administered with 300 mg of IV Vitamin C (IS + C) in random sequence. Serum samples for IL-1, IL-6, TNF-α and IL-10 and non-transferrin bound iron were obtained at baseline, 45 min and 105 min post study medication administration. Peripheral blood mononuclear cells were isolated at the same time points and stained with fluorescent probes to identify intracellular reactive oxygen species and mitochondrial membrane potential (Δψm) by flow cytometry. Lipid peroxidation was assessed by plasma F2-isoprosatane concentration. Both IS and IS + C were associated with increased plasma F2-isoprostanes concentrations post-infusion. Maximal plasma F2-isoprostane concentrations after IS + C were significantly elevated from baseline (234 ± 0.04 vs. 0.198 ± 0.028 ng/mL, p = 0.02). After IS + C, IL-1, IL-6, IL-10, and TNF-alpha were significantly elevated compared to baseline. After IS alone only IL-6 was noted to be elevated. Intracellular production of H(2)O(2) and loss of mitochondrial membrane potential (Δψm) was observed after IS while IS + C was associated with increased O (2) (·-) production. Both IS and IS + C induced serum cytokine activation accompanied by lipid peroxidation, however, IS + C induced higher plasma concentrations of F2-isoprostanes, IL-1, IL-10, and TNF-α post-infusion. Long-term safety studies of IV iron co-administered with Vitamin C are warranted.

Topics: Adult; Ascorbic Acid; Cross-Over Studies; Cytokines; Epoetin Alfa; Erythropoietin; F2-Isoprostanes; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Lipid Peroxidation; Male; Membrane Potential, Mitochondrial; Middle Aged; Oxidative Stress; Prospective Studies; Reactive Oxygen Species; Recombinant Proteins; Systems Biology

The effects of calcineurin inhibitors on oxidative stress after renal transplant are obscure. This study sought to investigate the changes in plasma oxidative stress and lipid levels in patients receiving cyclosporine or tacrolimus before and after renal transplant for 6 months.. Twenty-one patients and 15 healthy controls were involved in our study. Twelve of the patients were treated with cyclosporine and 9 were treated with tacrolimus. Plasma malondialdehyde, nitrite/nitrate, vitamin C, vitamin E, and plasma glutathione levels, as well as total cholesterol and triglyceride levels, were evaluated before and after transplant for 6 months.. Before the transplant, patients had higher malondialdehyde and plasma glutathione levels than did healthy controls (3.76 ± 0.79 nmol/mL vs 3.21 ± 0.57 nmol/mL; P < .05, and 66.6 ± 23.2 μmol/L vs 43.3 ± 26.9 μmol/L; P < .05). In the overall group of patients, a significant increase in malondialdehyde levels was detected 3 and 6 months after transplant (3.76 ± 0.79 nmol/mL vs 4.38 ± 0.87 nmol/mL in the third month; P = .02; and 3.76 ± 0.79 nmol/mL vs 4.28 ± 0.69 nmol/mL in the sixth month; P = .04). A significant reduction in plasma glutathione levels 1 month after transplant and nitrite/nitrate levels 6 months after transplant was found. No changes in vitamin C and vitamin E levels were detected before and after transplant. After 3 and 6 months of transplant, cyclosporine-treated patients had higher levels of total cholesterol and triglycerides when compared with tacrolimus-treated patients.. An enhancement in plasma malondialdehyde levels was found after transplant at 6-month follow-up. However, no significant change in vitamin C, vitamin E, nitrite/nitrate levels between patients and controls was recorded. Although both calcineurin inhibitors showed similar effects on oxidative stress, cyclosporine-treated patients had higher levels of total cholesterol and triglycerides.

Topics: Adult; Antioxidants; Ascorbic Acid; Calcineurin Inhibitors; Cyclosporine; Enzyme Inhibitors; Female; Follow-Up Studies; Glutathione; Humans; Kidney Failure, Chronic; Kidney Transplantation; Lipids; Male; Malondialdehyde; Middle Aged; Nitrates; Nitrites; Oxidative Stress; Tacrolimus; Vitamin E; Young Adult

Oxidative stress is known to be enhanced in hemodialysis patients, and one of its useful markers is plasma copper/zinc superoxide dismutase (Cu/Zn-SOD). The increase in plasma Cu/Zn-SOD can be inhibited by orally administered lipid-soluble vitamin E. We examined the antioxidative effects of water-soluble vitamin C administered orally on Cu/Zn-SOD levels in hemodialysis patients.. Vitamin C was orally administered to 16 maintenance hemodialysis patients before each dialysis session. Doses were increased from 200 to 1,000 mg over 3 months. The levels of plasma vitamin C and Cu/Zn-SOD and its mRNA expression in leukocytes were determined 1, 2, and 3 months after the start of vitamin C administration. Furthermore, the levels of oxidized and reduced forms of plasma vitamin C were determined before the start of vitamin C administration and before and after dialysis at 1,000-mg vitamin C doses.. Following oral administration, the plasma levels of vitamin C and its oxidized form were increased. However, significant changes in plasma Cu/Zn-SOD or its mRNA expression in leukocytes were not observed.. In maintenance hemodialysis patients, vitamin C administration resulted in a significant increase in the postdialysis level of the oxidized form of vitamin C, which suggested an increase in antioxidant effect. However, water-soluble vitamin C did not significantly suppress Cu/Zn-SOD expression enhancement.

Topics: Administration, Oral; Ascorbic Acid; Biomarkers; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Renal Dialysis; Superoxide Dismutase

It has been suggested that hemodialysis patients may be under increased oxidative stress and may therefore benefit from the long-term use of antioxidants (particularly for the reduction of the risk of heart disease). The aim of this study was, first, to evaluate the effect of hemodialysis by itself on lipid and lipoprotein oxidation profiles and, second, to analyze the effect of vitamin C supplementation in patients with end-stage renal disease starting hemodialysis. Forty-one patients with end-stage renal disease were enrolled and randomized to receive 1000 mg/d vitamin C or matching placebo before starting hemodialysis. We measured lipid profile and the susceptibility of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) to oxidation using copper ions at the moment of inclusion and after 1 year. All lipoperoxidation parameters were included. Hemodialysis by itself improved the lipid profile, lowering total cholesterol (176.4 +/- 48.4 to 154.2 +/- 28.8 mg/dL, P < .01), LDL cholesterol (94.1 +/- 39.6 to 76.1 +/- 26.6 mg/dL LDL, P < .03), and phospholipids levels (196.5 +/- 36.7 to 182.9 +/- 36.1 mg/dL, P < .05) in all patients on maintenance hemodialysis. The HDL cholesterol was also decreased (49.4 +/- 19.8 to 43.4 +/- 24.1 mg/dL HDL, P < .03). No significant differences were detected between patients receiving vitamin C and those receiving placebo. Thiobarbituric acid reactive substances (TBARS) and lipoperoxides increased in patients after a year of hemodialysis, but the difference was lower in those administered vitamin C for a year-TBARS LDL (in nanograms per gram LDL): 0.25 +/- 0.20 to 0.38 +/- 0.2 in vitamin C-treated subjects and 0.28 +/- 0.17 to 0.46 +/- 0.21 in those treated with placebo (P < .007); TBARS HDL (in nanograms per gram HDL): 0.22 +/- 0.12 to 0.34 +/- 0.30 in patients receiving vitamin C and 0.20 +/- 0.18 to 0.28 +/- 0.19 in those receiving placebo (P = .071). Hemodialysis by itself seems to improve the lipid profile in patients with a previous prooxidative state such as uremia. Although our results failed to demonstrate significant differences between vitamin C-treated and untreated patients, and despite the small number of patients, the trend toward a decrease in oxidation products due to vitamin C supplementation may be beneficial for oxidation parameters. This area remains controversial and under active investigation. Further research is necessary before a firm conclusion can be reached.

Topics: Antioxidants; Ascorbic Acid; Copper; Female; Humans; Kidney Failure, Chronic; Lipid Peroxidation; Lipids; Lipoproteins; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Thiobarbituric Acid Reactive Substances; Vitamin E

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Cyclosporine; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Probability; Reference Values; Risk Assessment; Transplantation Immunology; Treatment Outcome; Vitamin E

Topics: Administration, Oral; Adult; Aged; Ascorbic Acid; Biomarkers; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Isoprostanes; Kidney Failure, Chronic; Male; Middle Aged; Reference Values; Renal Dialysis; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome

Evidence indicates that oxidative stress is present in dialysis patients, and is associated with vitamin C deficiency. Limited data are available regarding the effects of vitamin C supplementation on oxidative stress and inflammation markers in these patients. Moreover, there are no data available on plasma polypeptide fingerprints by proteome analysis before and after vitamin C supplementation. Therefore, we analyzed plasma samples from a prospective, randomized, open-labeled trial to assess the effects of oral vitamin C supplementation (250 mg three times per week), to define the plasma polypeptide pattern in hemodialysis patients. Our results reveal that more than 30 polypeptides show significant changes in the dialysis patients in comparison to controls with normal renal function, and that several polypeptides are affected/normalized by oral vitamin C supplementation. These results underline the remarkable potential for proteomics to recognize specific peptide profiles in different pathological situations, which might not be detected by classical methods.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Dietary Supplements; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Proteomics; Renal Dialysis; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Chronic hemodialysis (HD) patients manifest anemia and atherosclerosis with associated oxidative stress. We explored whether intravenous infusion of vitamin C (VC) and/or use of vitamin E (VE)-coated dialysis membrane could palliate HD-evoked oxidative stress. Eighty patients undergoing chronic HD were enrolled and randomly assigned into four groups: HD with intravenous VC (n=20), HD with VE-coated dialyzer (n=20), HD with both (n=20), and HD with neither (n=20). We evaluated oxidative stress in blood and plasma, erythrocyte methemoglobin/ferricyanide reductase (red blood cells (RBC)-MFR) activity, plasma methemoglobin, and pro-inflammatory cytokines in these patients. All patients showed marked increases (14-fold) in blood reactive oxygen species (ROS) after HD. The types of ROS were mostly hydrogen peroxide, and in lesser amounts, O2*- and HOCl. HD resulted in decreased plasma VC, total antioxidant status, and RBC-MFR activity and increased plasma and erythrocyte levels of phosphatidylcholine hydroperoxide (PCOOH) and methemoglobin. Intravenous VC significantly palliated HD-induced oxidative stress, plasma and RBC levels of PCOOH, and plasma methemoglobin levels and preserved RBC-MFR activity. The VE-coated dialyzer effectively prevented RBCs from oxidative stress, although it showed a partial effect on the reduction of total ROS activity in whole blood. In conclusion, intravenous VC plus a VE-coated dialyzer is effective in palliating HD-evoked oxidative stress, as indicated by hemolysis and lipid peroxidation, and by overexpression of proinflammation cytokines in HD patients. Using VE-coated dialyzer per se is, however, effective in reducing lipid peroxidation and oxidative damage to RBCs.

Topics: Antioxidants; Ascorbic Acid; Cytokines; Erythropoietin; Female; Hemolysis; Humans; Hydrogen Peroxide; Infusions, Intravenous; Kidney Failure, Chronic; Lipid Peroxidation; Male; Membranes, Artificial; Methemoglobin; NADH, NADPH Oxidoreductases; Oxalates; Oxidative Stress; Phosphatidylcholines; Reactive Oxygen Species; Renal Dialysis; Spectrophotometry, Atomic; Vitamin E

Oxidative stress may contribute to the progression of chronic renal failure. In this study, cats with spontaneous renal insufficiency were fed a dry cat food supplemented with the antioxidants vitamins E and C, and beta-carotene for 4 weeks. When compared with healthy cats, cats with renal insufficiency had a tendency to oxidative stress. The antioxidant supplements significantly reduced DNA damage in cats with renal insufficiency as evidenced by reduced serum 8-OHdG and comet assay parameters. Therefore, supplements of vitamins E and C and beta-carotene as antioxidants may be beneficial to cats with renal disease.

Topics: Animal Feed; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Blood Urea Nitrogen; Cat Diseases; Cats; Creatinine; Cross-Over Studies; Dietary Supplements; Female; Kidney Failure, Chronic; Male; Oxidative Stress; Phosphorus; Vitamin E

Although erythropoietin (EPO)-hyporesponsive anemia in hemodialysis patients most commonly results from iron deficiency, the contributory role of chronic inflammation and oxidative stress in its pathogenesis is poorly understood. We conducted an open-label prospective study to assess the effect of vitamin C, an antioxidant, on EPO-hyporesponsive anemia in hemodialysis patients with unexplained hyperferritinemia.. Forty-six of 262 patients in an inner-city hemodialysis center met the inclusion criteria (administration of intravenous iron and EPO for > or = 6 months at a dose > or = 450 U/kg/wk, average 3-month hemoglobin [Hb] level < or = 11.0 g/dL [< or = 110 g/L], ferritin level > or = 500 ng/mL (microg/L), and transferrin saturation [TSAT] < or = 50%). Patients were excluded if they had a clear explanation for the EPO hyporesponsiveness. Four patients refused to participate. The remaining patients were randomly assigned; 20 patients to receive standard care and 300 mg of intravenous vitamin C with each dialysis session (group 1) and 22 patients to receive standard care only (group 2). Study duration was 6 months. During the study, 1 patient from group 1 was removed (upper gastrointestinal bleeding) from final analysis. Monthly assessment included Hb level, mean corpuscular volume, iron level, iron-binding capacity, ferritin level, TSAT, and Hb content in reticulocytes. In addition, biointact parathyroid hormone, aluminum, C-reactive protein (CRP), and liver enzymes were measured every 3 months.. Age, sex, race, and time on dialysis therapy were similar in both groups. At 6 months, Hb levels significantly increased from 9.3 to 10.5 g/dL (93.0 to 105.0 g/L) in group 1, but not group 2 (9.3 to 9.6 g/dL [93.0 to 96.0 g/L]; P = 0.0001). Similarly, TSAT increased from 28.9% to 37.3% in group 1, but not group 2 (28.7% to 29.3%; P = 0.0001). EPO dose (477 to 429 versus 474 to 447 U/kg/wk), iron-binding capacity (216 to 194 versus 218 to 257 microg/dL [38.7 to 34.7 versus 39 to 46 micromol/L]), and CRP level (2.8 to 0.9 versus 2.8 to 2.2 mg/dL) decreased significantly in group 1, but not in controls. Changes in Hb content in reticulocytes and ferritin level also were statistically significant in group 1. There was no change in biointact parathyroid hormone levels. Although serum iron levels and intravenous iron doses changed within each group, changes were equal between the 2 groups.. In hemodialysis patients with refractory anemia and hyperferritinemia, vitamin C improved responsiveness to EPO, either by augmenting iron mobilization from its tissue stores or through antioxidant effects.

Topics: Adult; Anemia; Antioxidants; Ascorbic Acid; Erythropoietin; Female; Ferritins; Humans; Injections, Intravenous; Iron Metabolism Disorders; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

Chronic hemodialysis (HD) patients increase erythrocyte susceptibility to hemolysis and impair cell survival. We explored whether electrolyte-reduced water (ERW) could palliate HD-evoked erythrocyte impairment and anemia. Forty-three patients undergoing chronic HD were enrolled and received ERW administration for 6 month. We evaluated oxidative stress in blood and plasma, erythrocyte methemoglobin (metHb)/ferricyanide reductase activity, plasma metHb, and proinflammatory cytokines in the chronic HD patients without treatment (n=15) or with vitamin C (VC)- (n=15), vitamin E (VE)-coated dialyzer (n=15), or ERW treatment (n=15) during an HD course. The patients showed marked increases (15-fold) in blood reactive oxygen species, mostly H(2)O(2), after HD without any treatment. HD resulted in decreased plasma VC, total antioxidant status, and erythrocyte metHb/ferricyanide reductase activity and increased erythrocyte levels of phosphatidylcholine hydroperoxide (PCOOH) and plasma metHb. Antioxidants treatment significantly palliated single HD course-induced oxidative stress, plasma and RBC PCOOH, and plasma metHb levels, and preserved erythrocyte metHb /ferricyanide reductase activity in an order VC>ERW>VE-coated dialyzer. However, ERW had no side effects of oxalate accumulation easily induced by VC. Six-month ERW treatment increased hematocrit and attenuated proinflammatory cytokines profile in the HD patients. In conclusion, ERW treatment administration is effective in palliating HD-evoked oxidative stress, as indicated by lipid peroxidation, hemolysis, and overexpression of proinflammatory cytokines in HD patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antioxidants; Ascorbic Acid; Biomarkers; Cell Survival; Electrolysis; Erythrocytes; Female; Hematocrit; Hemodialysis Solutions; Humans; Kidney Failure, Chronic; Male; Membranes, Artificial; Methemoglobin; Middle Aged; Oxidative Stress; Reactive Oxygen Species; Renal Dialysis; Vitamin E; Water

Ascorbate supplementation for patients on regular dialysis treatment (RDT) is advised to obviate deficiency and improve epoetin response in those with functional iron deficiency. However, clear-cut safety concerns regarding hyperoxalemia are still poorly understood. This study tries to establish safety/efficacy profiles of ascorbate and oxalate during long-term intravenous ascorbate supplementation.. A prospective study was performed in 30 patients on RDT showing ascorbate deficiency (plasma ascorbate < 2.6 mg/L [<15 micromol/L]): 18 patients were administered intravenous ascorbate during 18 months (250 mg/wk, subsequently increased to 500 mg), and 12 patients were taken as reference untreated cases. Plasma ascorbate and oxalate assays and dialytic balance determinations were performed (ion chromatography and reverse-phase high-performance liquid chromatography, respectively) at baseline, during treatment, and 12 months after withdrawal.. Plasma ascorbate levels increased dose dependently with supplementation (1.6 +/- 0.8 mg/L [9.1 +/- 4.6 mumol/L] at baseline, 2.8 +/- 1.8 mg/L [15.9 +/- 10.1 micromol/L]) with 250 mg of ascorbate, and 6.6 +/- 2.8 mg/L [37.5 +/- 16.0 micromol/L] with 500 mg/wk of ascorbate), but only normalized with greater dosages for several months in 94% of patients. Baseline plasma oxalate levels increased from 3.2 +/- 0.8 mg/L (35.8 +/- 8.8 micromol/L) to 3.6 +/- 0.8 mg/L (39.5 +/- 9.1 micromol/L) and 4.5 +/- 0.9 mg/L (50.3 +/- 10.4 micromol/L) with 250 and 500 mg, respectively ( P < 0.001). The calcium oxalate saturation threshold was exceeded by 7 of 18 patients (40%) during 6 months therapy with 500 mg/wk. Ascorbate dialysis removal increased from 37.8 +/- 23.2 mg (215 +/- 132 micromol) to 99.6 +/- 51.7 mg (566 +/- 294 micromol) during supplementation (P < 0.001), with corresponding increases in oxalate removal from 82.5 +/- 33.2 mg (917 +/- 369 micromol) to 111.2 +/- 32.6 mg/L (1,236 +/- 362 micromol; P < 0.01). Withdrawal reverted plasma levels and dialysis removal to initial values. Values for untreated patients did not change during 1 year of follow-up.. Patients on RDT may resolve ascorbate deficiency with intravenous supplementation of 500 mg/wk, but this implies a significant risk for oxalate supersaturation. Oxalate measurements are strongly recommended during long-term ascorbate therapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Ascorbic Acid; Ascorbic Acid Deficiency; Calcium Oxalate; Drug Resistance; Erythropoietin; Female; Humans; Hyperoxaluria; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

The aim of the study was to analyze the lipid and lipoprotein oxidation profile in patients with end stage renal disease who started haemodialysis and also to evaluate the possible effect of haemodialysis and vitamin C supplementation on lipoprotein oxidation one year after the initiation of the therapy.. Forty-one end stage renal disease patients who started haemodialysis between January 1999 and January 2000 were enrolled in the study. The patients were randomised to receive 1,000 mg/day of vitamin C or placebo and then hemodialysis was initiated. We measured the lipid profile and the susceptibility of LDL and HDL to oxidation using cooper ions, at the moment of inclusion and one-year after the treatment.. No significant differences were observed among the vitamin-C treated patients and those who received placebo. Our results show that haemodialysis by itself did not induce deletereous effects on the lipid profile, which was slightly improved. A small decrease in total cholesterol--183 to 164 mg/dl (group A), 170 to 144 mg/dl (group B); in LDL cholesterol (100 mg/dl to 79 mg/dl (group A), 88 mg/dl to 73 mg/dl (Group B); and in phospholipids [198 to 188 mg/dl, group A (Group A), 195 mg/dl to 178 mg/dl (Group B)], was observed in all the patients one year after starting haemodialysis. When considering oxidation-derivative products, the lag phase of LDL-cholesterol and HDL-cholesterol was enlarged but without statistical significance. A tendency to increase the vitamin E generation in HDL and LDL lipoproteins was observed in vitamin-C treated patients, but the difference still remained not significant.. Haemodialysis by itself could improve lipid profile in patients with a previous pro-oxidative state such as uraemia. Although our results have failed to demonstrate significant differences between vitamin C-treated and not treated patients, the tendency to decrease oxidation products by supplementation of vitamin C could mean a beneficial effect on oxidation parameters. In order to improve oxidative stress, the use of lipophylic more than hydrophilic vitamins could be evaluated in randomized studies with a more important number of patients.

Topics: Ascorbic Acid; Atherosclerosis; Female; Humans; Kidney Failure, Chronic; Lipid Peroxidation; Lipoproteins; Male; Middle Aged; Renal Dialysis; Vitamins

There is increasing evidence for the presence of oxidative stress and vitamin C deficiency in dialysis patients. Limited data, however, are available regarding the effects of vitamin C supplementation on oxidative stress and inflammation markers in such patients.. We ran a prospective, randomized, open-label trial to assess the effects of oral vitamin C supplementation (250 mg three times per week) for 2 months on well-defined oxidative and inflammatory markers in 33 chronic haemodialysis (HD) patients.. Normalization of plasma total vitamin C and ascorbate levels by oral vitamin C supplementation did not modify plasma levels of carbonyls, C-reactive protein and albumin, or erythrocyte concentrations of reduced and oxidized glutathione.. Short-term oral vitamin C supplementation did not modify well-defined oxidative/antioxidative stress and inflammation markers in HD patients. Whether a higher oral dose or the intravenous route can modify these markers remains to be determined.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Dietary Supplements; Female; Hemoglobins; Humans; Inflammation; Iron; Kidney Failure, Chronic; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Smoking

This study focused on the effect of vitamin C on the 8-hydroxy-2'-deoxyguanosine (8-OHdG) level of cellular DNA, as well as 8-oxoguanine-DNA glycosylase 1 (hOGG1) and human MutT homologue (hMTH1) gene expression in peripheral blood lymphocytes of chronic hemodialysis patients.. Sixty chronic hemodialysis patients (35 men and 25 women) were recruited to participate in a randomized, placebo-controlled study. Treatment order is block-randomized with intravenous sodium ascorbate (vitamin C, 300 mg) or placebo (0.9% saline), administered postdialysis three times a week. We evaluated 8-OHdG level, intracellular reactive oxygen species (ROS) production, and gene expression of hOGG1 and hMTH1 in peripheral blood lymphocytes by using high-performance liquid chromatography (HPLC) electrochemical detection method, flow cytometric analysis, and reverse transcription-polymerase chain reaction (RT-PCR), respectively.. A total of 51 patients completed the study (26 in placebo group and 25 in vitamin C group). Mean 8-OHdG levels significantly decreased in total subjects following 8 weeks of vitamin C supplementation (22.9 vs. 18.8/10(6) dG, P < 0.01). The decrease in 8-OHdG levels after vitamin C supplementation was also noted in the patients with ferritin <500 or > or =500 microg/L and transferrin saturation (TSAT) <50 or > or =50% (P < 0.05). But 8-OHdG levels had no significant changes in total patients or in the four subgroups of patients treated with placebo as compared to their baselines. Intracellular ROS production by lymphocytes from the four subgroups of patients, either spontaneous (P < 0.05) or phorbol-12-myristate-13-acetate (PMA)-stimulated (P < 0.001), was significantly reduced after 8 weeks vitamin C supplementation. Steady-state hOGG1 mRNA levels were significantly up-regulated at 24 hours after vitamin C administration (P < 0.05), but hMTH1 mRNA levels were not. The changes in the spontaneous and PMA-stimulated ROS production, and an up-regulation of hOGG1 mRNA expression were not observed in patients treated with placebo as compared to their baselines.. Vitamin C supplementation in chronic hemodialysis patients can reduce the lymphocyte 8-OHdG levels and intracellular ROS production, as well as up-regulate hOGG1 gene expression for repair. There is no compelling evidence for an in vivo pro-oxidant effect of vitamin C on lymphocyte DNA base oxidation, even in the status of increased iron stores.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Antioxidants; Ascorbic Acid; Deoxyguanosine; DNA Glycosylases; DNA Repair Enzymes; Female; Ferritins; Humans; Iron; Kidney Failure, Chronic; Lymphocytes; Male; Middle Aged; Oxidative Stress; Phosphoric Monoester Hydrolases; Reactive Oxygen Species; Renal Dialysis; RNA, Messenger; Transferrin; Up-Regulation

To investigate if oral use of Sorbifer Durules (EGIS Pharmaceutical Ltd, Budapest, Hungary) (1 tablet/d) is adequate for the maintenance of serum iron and vitamin C in normal range during recombinant human erythropoietin treatment in hemodialyzed patients. One tablet of Sorbifer Durules contains 100 mg of Fe(2+) and 60 mg of vitamin C.. Short-term, open-label clinical trial.. Hemodialysis units.. Twenty-four adult patients with end-stage renal disease on hemodialysis.. Four-week treatment period of Sorbifer Durules, preceded and followed by iron and vitamin C washout periods.. Fasting predialysis serum samples were collected on days 0, 28, 56, and 84 to determine hematocrit, blood hemoglobin, serum iron, total iron-binding capacity, transferrin saturation, ferritin, vitamin C, and plasma oxalate.. Four-week treatment in hemodialyzed patients by Sorbifer Durules led to significant increase of hematocrit, blood hemoglobin, serum iron and vitamin C. This treatment did not influence the level of plasma oxalate.. Oral dose of one tablet of Sorbifer Durules per day is adequate for the maintenance of serum iron in normal range during recombinant human erythropoietin treatment in hemodialyzed patients. This treatment simultaneously prevented the development of serum vitamin C deficiency and did not lead to further increase of plasma oxalate in these patients.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Ascorbic Acid; Creatinine; Erythropoietin; Female; Ferritins; Hematocrit; Hemoglobins; Humans; Iron; Iron Deficiencies; Iron, Dietary; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Recombinant Proteins; Renal Dialysis; Transferrin

Chronic renal failure is associated with impaired endothelium-dependent vasodilation and accelerated atherogenesis. To examine whether endogenous reactive oxygen species (ROS) modify endothelial function in renal failure, we evaluated the effect of the antioxidant vitamin C on endothelium-dependent responses in both the conduit and resistance vasculature of subjects with severe renal impairment.. Endothelial function of the forearm resistance vasculature was assessed using plethysmography to measure the dilator response to intra-arterial acetylcholine (Ach) (25 to 100 nmol/min). Endothelial function of radial and brachial arteries was assessed using vascular ultrasound to measure the dilator response to flow during reactive hyperemia [flow-mediated dilatation (FMD)]. Studies were performed before and after administration of vitamin C by intra-arterial infusion (25 mg/min) in 33 predialysis patients or by intravenous infusion (3 g) in 17 hemodialysis patients.. Parenteral administration of vitamin C resulted in a 100-fold increase (intra-arterial studies) and a 4.5-fold increase (intravenous studies) in serum antioxidant activity. Vitamin C administration increased the dilator response to ACh in resistance vessels (P = 0.01), but did not alter the dilator response to flow in conduit vessels of either dialysis (P = 0.3) or predialysis subjects (P = 0.8). In the presence of the nitric oxide (NO) synthase inhibitor NGmonomethyl-L-arginine (L-NMMA), there was no effect of vitamin C on resistance vessel endothelial function. In all cases the dilator response to the endothelium-independent dilators was unaffected by vitamin C.. Acute administration of vitamin C reduces oxidant stress in renal failure and improves NO-mediated resistance vessel dilatation.

Topics: Adult; Antioxidants; Ascorbic Acid; Biomarkers; Brachial Artery; Endothelium, Vascular; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Radial Artery; Renal Dialysis; Vascular Resistance; Vasodilation

Vitamin C has been reported to be an effective adjuvant agent in the treatment of anemia in iron-overloaded hemodialysis patients. We aim to evaluate its effect on erythropoietin (EPO) response in a prospective, randomized, double-blind, crossover study.. Sixty-three patients were randomly divided into two groups. Group 1 was treated with intravenous vitamin C, 500 mg, three times a week, and group 2, with placebo for 6 months. During the second 6-month period, group 1 was treated with placebo, and group 2, with the same dose of vitamin C. Thirty patients in group 1 and 28 patients in group 2 completed the study. Hemoglobin levels, weekly EPO dose, and ratio of EPO to hemoglobin as an index of EPO need were determined at both baseline and the end of the two periods, together with other parameters known to be associated with EPO response.. Twenty patients in group 1 (66.7%) and 18 patients in group 2 (64.3%) were responsive to vitamin C. In both groups, vitamin C resulted in a significant increase in hemoglobin levels (P < 0.0001 for both) and a significant decrease in EPO-hemoglobin ratio (P < 0.0001, P = 0.019). Transferrin saturation also increased with vitamin C treatment in both groups (P = 0.009, P = 0.005). All these parameters remained stable with placebo in both groups. Other parameters did not change throughout the study.. Vitamin C can be used as an effective adjuvant therapy to EPO in hemodialysis patients. Further studies are needed to determine possible predictors of hematologic response to vitamin C.

Topics: Adult; Anemia; Ascorbic Acid; Cross-Over Studies; Double-Blind Method; Drug Interactions; Erythropoietin; Female; Hemoglobins; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Transferrin; Treatment Outcome

Ascorbic acid supplementation has been recommended to circumvent resistance to erythropoietin, which sometimes occurs in iron-overloaded uremic patients. In considering the pro-oxidant effect of ascorbic acid, the authors hypothesize that adjuvant therapy with larger doses of ascorbic acid in hemodialysis patients with iron overload may raise the risk of increasing free radical generation. The oxidative stress of intravenous ascorbic acid supplementation in hemodialysis patients was evaluated in this study.. Six healthy subjects and 29 hemodialysis patients were enrolled. Chemical scavenging activity of various compounds was measured by in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Free radical generation was determined in vitro by lucigenin-enhanced chemiluminescence (LucCL) assay on blood samples. Blood biochemistries were also measured simultaneously in hemodialysis patients 1 minute before and 5 minutes later in the presence or absence of intravenous injection of 300 mg ascorbic acid.. Ascorbic acid presented a strong antioxidant effect in DPPH chemical reaction. On the contrary, it exerted pro-oxidant effect when mixed with plasma or whole blood of healthy subjects and hemodialysis patients. The pro-oxidant effect of ascorbic acid detected by LucCL was attenuated by various iron chelators and superoxide dismutase. In hemodialysis patients, the changes of LucCL intensity were significantly higher in the ascorbic acid-treated group than those in the control group (1261.0 +/- 401.9 v 77.4 +/- 62.5 relative light unit [RLU]; P < 0.05). Adjuvant ascorbic acid therapy resulted in significantly higher LucCL intensity in hemodialysis patients with ferritin > or =600 ng/mL (1,348.2 pmol/L) than those with ferritin less than 600 ng/mL (2,296.0 +/- 763.8 v 414.3 +/- 88.0 RLU; P<0.05). The changes of LucCL intensity were positively correlated with serum ferritin level (R2=0.8673; P<0.05). However, there was no significant correlation between the responses of LucCL intensity to ascorbic acid administration and transferrin saturation (R2=0.195; P=0.0665).. Persons with excess ascorbic acid supplement in the blood or plasma generate iron-chelator-suppressible chemiluminescents suggestive of free radical formation. Whether the findings occur in vivo or that the free radicals generated in vitro lead to toxicity in patients is not known from this study. These results suggest that either lower parenteral dose or lower infusion rate of ascorbic acid may be more appropriate for adjuvant therapy in iron-overloaded uremic patients.

Topics: Aged; Antioxidants; Ascorbic Acid; Biphenyl Compounds; Female; Ferritins; Free Radical Scavengers; Free Radicals; Humans; Hydrazines; In Vitro Techniques; Injections, Intravenous; Iron; Iron Overload; Kidney Failure, Chronic; Luminescent Measurements; Male; Middle Aged; Oxidative Stress; Picrates; Renal Dialysis

Vitamin E supplementation could elevate circulating vitamin E metabolites while modulating oxidative and inflammatory status in end-stage renal failure patients undergoing hemodialysis. Plasma concentrations of carboxyethyl-hydroxychromanols (alpha- and gamma-CEHC), ascorbic acid, alpha- and gamma-tocopherols, F2-isoprostanes, and inflammatory biomarkers [tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP)] were measured in blood samples obtained from patients (n = 11) before and after dialysis on two occasions prior to, and at 1 and 2 mon of daily vitamin E supplementation (400 IU RRR-alpha-tocopherol). Supplementation nearly doubled plasma alpha-tocopherol concentrations (from 18 +/- 0.5 to 31 +/- 1.7 microM, P < 0.0001), whereas gamma-tocopherol concentrations decreased (from 2.8 +/- 0.3 to 1.7 +/- 0.2 microM, P = 0.001). Serum alpha-CEHC increased 10-fold from 68 +/- 3 to 771 +/- 175 nM (P < 0.0001), and gamma-CEHC increased from 837 +/- 164 to 1136 +/- 230 nM (P = 0.008). Vitamin E supplementation also increased postdialysis hematocrits from 38 +/- 1% to 41 +/- 1% (P < 0.001). Dietary antioxidant intakes (vitamins E and C) were low in most subjects; plasma ascorbic acid levels (88 +/- 27 microM) decreased significantly with dialysis (33 +/- 11 microM, P = 0.01). Plasma IL-6, CRP, TNF-alpha, and free F2-isoprostane concentrations were elevated throughout the study. There is a complex relationship between chronic inflammation and oxidative stress that is not mitigated by short-term vitamin E supplementation. Importantly, serum vitamin E metabolite concentrations that increased 10-fold within 30 d of supplementation did not increase further, suggesting routes other than urine for removal of metabolites.

Topics: Aged; Antioxidants; Ascorbic Acid; Biological Availability; C-Reactive Protein; Dietary Supplements; Erythropoietin; Female; Ferritins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Solubility; Vitamin E

Muscle cramps that improve after carnitine or vitamin E therapies are common in haemodialysis (HD) patients. Because vitamin C participates in carnitine biosynthesis, and its levels are reduced in uraemia, subclinical vitamin C depletion may contribute to HD cramps. Our aim was to determine the effects of vitamins C, E and their combination on the frequency and intensity of HD cramps.. In this placebo-controlled, double-blind study, 60 HD-patients were randomized into four therapeutic groups. Each group (n=15) received six identical capsules daily for 8 weeks, containing one of the following: vitamin E (400 mg), vitamin C (250 mg), their combination, or placebo.. The frequency and intensity of HD cramps decreased significantly in all three vitamin groups compared with the placebo group at the end of the trial, and compared with the pre-treatment values. At the end of the trial, vitamins E, C, their combination, and placebo produced cramp reductions of 54, 61, 97 and 7%, respectively. The percentage cramp reduction had no significant correlation with age, sex, aetiology of end-stage renal disease, serum electrolytes or HD duration, but showed a positive correlation (r=0.33, P=0.01) with the type of therapy. No vitamin-related adverse effects were encountered during the trial.. Short-term treatment with the combination of vitamins E and C is safe and effective in reducing HD cramps; however, its safety for prolonged therapy has yet to be evaluated in HD patients.

Topics: Ascorbic Acid; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Electrolytes; Female; Hematocrit; Humans; Kidney Failure, Chronic; Male; Middle Aged; Muscle Cramp; Placebos; Renal Dialysis; Vitamin E

The aim of this study was to investigate the lipid-lowering effect of vitamins compared to placebo and their short-term supplementation safety in patients on hemodialysis.. Eighty-four hemodialysis patients were randomly allocated to four therapeutic groups. Each group (n = 21) received one of the following treatments: vitamin C (200 mg), E (200 mg), D3 (50,000 IU) or placebo daily. Serum triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were measured before and following 3 months of vitamin therapy.. LDL-c and total cholesterol levels as well as the ratios of LDL-c to HDL-c and cholesterol to HDL-c significantly decreased after vitamin C therapy. Triglyceride and the ratio of triglyceride to HDL-c significantly decreased following vitamin D3 therapy. HDL-c increased and the ratio of LDL-c to HDL-c decreased significantly after vitamin E therapy. No major side-effects were encountered during the 3 months' trial.. Short-term supplementary vitamins are safe and beneficial for treatment of lipid abnormalities in hemodialysis patients.

Topics: Adult; Ascorbic Acid; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Lipids; Male; Renal Dialysis; Vitamin D; Vitamin E

8-Hydroxy 2'-deoxyguanosine (8-OHdG) of leukocyte DNA has been identified as a surrogate marker of oxidative stress in chronic hemodialysis (HD) patients. In this study, we focused on the determinants of the 8-OHdG level in leukocyte DNA of HD patients. We further investigated the influence of vitamin E-modified, regenerated cellulose (CL-E) membrane on the oxidative DNA damage, intracellular reactive oxygen species (ROS) production of granulocytes, and plasma alpha-tocopherol concentration.. 8-OHdG content in cellular DNA of leukocytes was measured by a high-performance liquid chromatography-electrochemical detection (HPLC-ECD) method. Intracellular production of ROS, H2O2 and O2-. were analyzed by flow cytometry in leukocytes with and without phorbol-12-myristate-13-acetate (PMA) stimulation before dialysis, as well as at 15 and 30 minutes of dialysis. Plasma alpha-tocopherol concentration was measured by a HPLC method, and the value of alpha-tocopherol was corrected by total blood lipid concentration.. In the prospective cross sectional study, the mean 8-OHdG level in leukocyte DNA was equally lower in the patients of the CL-E, polymethylmethacrylate (PMMA), and polysulfone (PS) groups as compared with the cellulosic group (ANOVA, P < 0.001). The leukocyte 8-OHdG level correlated negatively with plasma alpha-tocopherol and blood lipid-adjusted plasma alpha-tocopherol, but correlated positively with serum iron and percentage of transferrin saturation. Forward stepwise multiple regression showed that dialysis membrane type, serum iron, and blood lipid-adjusted plasma alpha-tocopherol were the independent determinants of the leukocyte 8-OHdG level in HD patients. Like synthetic membranes, granulocyte ROS production was less augmented during dialysis with the CL-E membrane as compared with the cellulose membrane. Exposure to cellulose membrane impaired intracellular ROS production of granulocytes in response to PMA challenge, whereas the CL-E and synthetic membranes improved the granulocyte responsiveness to PMA. In the longitudinal cross-over study, the 8-OHdG level significantly decreased, and blood lipid-adjusted plasma alpha-tocopherol increased after switching the cellulose membrane to CL-E or synthetic membrane for eight weeks. In contrast, the 8-OHdG level dramatically rose, and blood lipid-adjusted plasma alpha-tocopherol declined after shift of CL-E or synthetic membrane to the cellulose membrane.. CL-E membrane exhibited biocompatible and bioactive characteristics. Like synthetic membranes, treatment with a CL-E dialyzer effectively reduced the 8-OHdG content in leukocyte DNA, suppressed intracellular ROS production of granulocytes, and preserved the plasma level of vitamin E. It could further improve granulocyte responsiveness to a PMA challenge. Reduced DNA damage and improved immune function of leukocytes may reduce the cancer and infection risks in chronic HD patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Ascorbic Acid; Biocompatible Materials; Bone Cements; Cellulose; Chromatography, High Pressure Liquid; Cross-Over Studies; Deoxyguanosine; DNA; Female; Flow Cytometry; Humans; Hydrogen Peroxide; Kidney Failure, Chronic; Leukocytes; Male; Membranes, Artificial; Middle Aged; Oxidative Stress; Polymers; Polymethyl Methacrylate; Prospective Studies; Renal Dialysis; Sulfones; Vitamin E

Patients with renal disease receiving dialysis therapy are susceptible to a deficit in ascorbic acid (AA) caused by loss during dialysis and a restricted dietary AA intake. In previous studies, in such patients, the methods generally used for AA determination are non-specific and insensitive, and control of the easily deteriorating AA in the samples is often disregarded. The purpose of this work was to study the AA plasma levels and dialyser clearances as well as the kinetics of administered AA in a group of dialysis patients, using selective and sensitive methodology and a procedure preserving the AA sample content.. Using an analytical method based on high-performance liquid chromatography and electrochemical detection, we have examined the dialyser clearance of AA as well as the pre- and post dialysis plasma levels of AA in patients on chronic dialysis therapy. The plasma AA levels were further measured after single and multiple dose supplementation of 200 mg p.o. per day.. The majority of the patients (16 of 19) had pre-dialysis plasma levels below the normal range. The dialyser clearance of AA was 212 ml/min (median value). Following dialysis, the plasma AA concentrations were reduced by a median of 33%. AA supplementation significantly increased these levels; however, they dropped soon after supplementation was stopped. AA in uraemic whole blood and plasma was, on average, less stable than in samples from healthy subjects.. This study, using selective analytical method with adequate stability control, confirms that AA is readily removed by conventional haemodialysis membranes. Patients on chronic haemodialysis have remarkably low plasma AA levels unless given AA supplementation.

Topics: Adult; Aged; Ascorbic Acid; Dietary Supplements; Dose-Response Relationship, Drug; Drug Stability; Humans; Kidney Failure, Chronic; Kinetics; Metabolic Clearance Rate; Middle Aged; Renal Dialysis; Time Factors

The peritoneal clearance and peritoneal transfer of oxalic acid, vitamin C, and vitamin B6 in 32 patients during continuous ambulatory peritoneal dialysis (CAPD) using peritoneal dialysis solutions containing 1.5% or 2.5% glucose were examined. The plasma level of oxalic acid was significantly elevated in all patients, plasma vitamin C was in the normal range or in the upper margin of the normal range, and plasma vitamin B6 was in the normal range. The peritoneal clearance of oxalic acid was significantly lower, and the peritoneal clearance of vitamin B6 was the lowest in comparison to the peritoneal clearance of urea. With the exception of vitamin B6, the peritoneal clearance and peritoneal transfer of the examined parameters increased using the dialysis solution containing 2.5% glucose. We found direct relationships between the plasma levels of oxalic acid and creatinine as well as plasma vitamin C and between the peritoneal transfer of oxalic acid and the peritoneal transfer of vitamin C as well as vitamin B6. The significant hyperoxalemia of our patients was found to persist despite the relatively high peritoneal transfer of oxalic acid during CAPD. These results suggest that CAPD is not a method effective enough for permanent reduction of the plasma levels of oxalic acid.

Topics: Adult; Ascorbic Acid; Dietary Proteins; Diuretics; Female; Furosemide; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Pyridoxine; Urea

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Ascorbic Acid; Dimethylnitrosamine; Duodenum; Female; Humans; Kidney Failure, Chronic; Liver; Male; Middle Aged; Stomach

Topics: Adult; Ampicillin; Ascorbic Acid; Bacteriuria; Chronic Disease; Diuresis; Female; Humans; Kidney Failure, Chronic; Male; Prospective Studies; Pyelonephritis; Recurrence; Sulfadimethoxine; Urinary Tract Infections

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.

Topics: Ascorbic Acid; Child; Child, Preschool; Humans; Hyperoxaluria; Infant; Kidney Failure, Chronic; Oxalates; Renal Dialysis; Renal Insufficiency, Chronic; Vitamins

Oxalate kidney injury can manifest as oxalate nephropathy or nephrolithiasis and present as acute kidney injury or even as end-stage renal disease. There are several known causes for acute oxalate nephropathy; however, the combination of exocrine pancreatic insufficiency with overconsumption of vitamin C has not been described before. In this case, a man in his early 80s presented with anorexia and extreme fatigue for 1 week. He had a history of myalgic encephalomyelitis, also known as chronic fatigue syndrome, for which he took several supplements, including high doses of vitamin C. Furthermore, several years ago, he was diagnosed elsewhere with exocrine pancreatic insufficiency. On admission, acute kidney injury was diagnosed. The kidney biopsy showed oxalate nephropathy as the cause. We diagnosed acute oxalate nephropathy due to high vitamin C doses and exocrine pancreatic insufficiency. Within 14 days, his kidney function got worse and he required renal replacement therapy.

Topics: Acute Disease; Acute Kidney Injury; Aged, 80 and over; Ascorbic Acid; Exocrine Pancreatic Insufficiency; Humans; Hyperoxaluria; Kidney; Kidney Failure, Chronic; Male; Oxalates; Renal Replacement Therapy

We report a case of systemic oxalosis involving the eyes and joints due to long-term use of high-dose vitamin C in a patient receiving maintenance peritoneal dialysis (PD). This 76-year-old woman with autosomal dominant polycystic kidney disease underwent living unrelated kidney transplantation 10 years earlier. The transplant failed 6 months before presentation, and she initiated hemodialysis therapy before transitioning to PD therapy 4 months later. During the month before presentation, the patient noted worsening arthralgias and decreased vision. Ophthalmologic examination revealed proliferative retinopathy and calcium oxalate crystals. Plasma oxalate level was markedly elevated at 187 (reference range, <1.7) μmol/L, and urine oxalate-creatinine ratio was high (0.18mg/mg). The patient reported taking up to 4g of vitamin C per day for several years. Workup for causes of primary and secondary hyperoxaluria was otherwise negative. Vitamin C use was discontinued, and the patient transitioned to daily hemodialysis for 2 weeks. Plasma oxalate level before the dialysis session decreased but remained higher (30-53μmol/L) than typical for dialysis patients. Upon discharge, the patient remained on thrice-weekly hemodialysis therapy with stabilized vision and improved joint symptoms. This case highlights the risk of high-dose vitamin C use in patients with advanced chronic kidney disease, especially when maintained on PD therapy.

Topics: Aged; Ascorbic Acid; Calcium Oxalate; Dose-Response Relationship, Drug; Female; Humans; Hyperoxaluria; Kidney Failure, Chronic; Peritoneal Dialysis; Polycystic Kidney, Autosomal Dominant; Retinal Diseases; Treatment Outcome; Vitamins; Withholding Treatment

Topics: Aged; Arthralgia; Ascorbic Acid; Blindness; Female; Fluorescein Angiography; Humans; Hyperoxaluria; Kidney Failure, Chronic; Renal Dialysis; Retinal Hemorrhage; Retinal Vessels; Tomography, Optical Coherence; Visual Acuity; Vomiting

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.

Topics: Ascorbic Acid; Cross-Sectional Studies; Erythrocytes; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Oxidative stress has been linked to disease progression, including chronic renal failure (CRF). The aim of the present study was to determine malondialdehyde (MDA) as a sign of lipid peroxidation, and to investigate the association between antioxidant activities and three trace elements, in 49 patients with CRF. The erythrocyte and plasma trace elements [selenium (Se), zinc (Zn), and copper (Cu)] and antioxidant defense levels were determined: glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), vitamins E and C. The obtained values were compared with 42 age- and sex-matched healthy controls. There were significantly lower mean values of plasma Se, GPx, vitamins E and C, erythrocyte Se, SOD and CAT levels in the patient group compared to the control group (p < 0.001). Plasma MDA showed a significant increase in all CRF patients in comparison with controls. No significant difference was found in plasma Cu, Zn, and erythrocyte GPx, Cu and Zn levels between patient and control groups. These findings indicate oxidative stress is present in patients of CRF, and may serve to establish a simple protocol for evaluation of renal function.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Case-Control Studies; Catalase; Copper; Erythrocytes; Female; Glutathione Peroxidase; Humans; Kidney Failure, Chronic; Male; Malondialdehyde; Middle Aged; Selenium; Superoxide Dismutase; Trace Elements; Vitamin E; Zinc

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.

Topics: Ascorbic Acid; Child; Dialysis Solutions; Female; Gingival Hemorrhage; Humans; Kidney Failure, Chronic; Peritoneal Dialysis; Renal Dialysis; Scurvy

Chronically haemodialysed end-stage renal disease patients are at high risk of morbidity arising from complications of dialysis, the underlying pathology that has led to renal disease and the complex pathology of chronic kidney disease. Anaemia is commonplace and its origins are multifactorial, involving reduced renal erythropoietin production, accumulation of uremic toxins and an increase in erythrocyte fragility. Oxidative damage is a common risk factor in renal disease and its co-morbidities and is known to cause erythrocyte fragility. Therefore, we have investigated the hypothesis that specific erythrocyte membrane proteins are more oxidised in end-stage renal disease patients and that vitamin C supplementation can ameliorate membrane protein oxidation. Eleven patients and 15 control subjects were recruited to the study. Patients were supplemented with 2 × 500 mg vitamin C per day for 4 weeks. Erythrocyte membrane proteins were prepared pre- and post-vitamin C supplementation for determination of protein oxidation. Total protein carbonyls were reduced by vitamin C supplementation but not by dialysis when investigated by enzyme linked immunosorbent assay. Using a western blot to detect oxidised proteins, one protein band, later identified as containing ankyrin, was found to be oxidised in patients but not controls and was reduced significantly by 60% in all patients after dialysis and by 20% after vitamin C treatment pre-dialysis. Ankyrin oxidation analysis may be useful in a stratified medicines approach as a possible marker to identify requirements for intervention in dialysis patients.

Topics: Ankyrins; Ascorbic Acid; Erythrocyte Membrane; Humans; Kidney Failure, Chronic; Oxidation-Reduction; Renal Dialysis

To determine the prevalence of vitamin C (ascorbic acid [AA]) deficiency in patients with end-stage renal disease, the effect of supplemental AA on plasma AA concentrations, and the extrinsic and intrinsic factors that affect plasma AA concentrations in this patient population.. In study 1, we compared the effect of hemodialysis (HD) on plasma AA concentrations between patients with low and high pre-HD AA concentrations. In study 2, we analyzed kinetic and nonkinetic factors for their association with increased plasma AA concentrations in patients on maintenance HD. Study 1 was performed in a single outpatient HD clinic in Cherry Hill, New Jersey. Study 2 was performed in 4 outpatient HD clinics in Southern New Jersey.. In study 1, we collected plasma samples from 8 adult patients on maintenance HD at various time points around their HD treatment and assayed them for AA concentration. In study 2, we enrolled 203 adult patients and measured pre-HD plasma AA concentrations. We ascertained supplemental AA use and assessed dietary AA intake.. In study 1, plasma AA concentrations were compared during the intradialytic and interdialytic period. In study 2, pre-HD plasma AA concentrations were correlated with supplement use and demographic factors.. Study 1 showed that over the course of a single HD treatment, the plasma AA concentration decreased by a mean (±standard deviation) of 60% (±6.6). In study 2, the median pre-HD plasma AA concentration was 15.7 μM (interquartile range, 8.7-66.8) in patients who did not take a supplement and 50.6 μM (interquartile range, 25.1-88.8) in patients who did take a supplement (P < .001). Supplement use, increasing age, and diabetes mellitus were associated with a pre-HD plasma AA concentration ≥30 μM.. HD depletes plasma AA concentrations, and AA supplementation allows patients to achieve higher plasma AA concentrations.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Diabetes Complications; Diet; Dietary Supplements; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

Renal oxalate deposition can be seen with primary hyperoxaluria, malabsorptive states, ethylene glycol toxicity and, rarely, with excessive vitamin C ingestion. We report a case of secondary hyperoxaluria in which the diagnosis was not considered initially because there was no past history of urinary calculi and no evidence of nephrocalcinosis on plain X-ray of the abdomen and ultrasonography. The disease was detected and diagnosed only after kidney transplantation. Secondary oxalosis can cause graft loss or delayed graft function. Biopsy of the allograft should be carefully examined for oxalate deposits even in the absence of a family history. When oxalosis is diagnosed, intensifying hemodialysis (HD) to eliminate calcium oxalate can help in the recovery of renal function in some cases. Systematic vitamin C supplementation in HD patients should be avoided as it can be a cause of secondary oxalosis.

Topics: Adult; Ascorbic Acid; Biopsy; Female; Humans; Hyperoxaluria; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Renal Dialysis; Treatment Outcome

We aimed to estimate dietary intakes of trace elements, minerals, and vitamins in hemodialysis patients (HDP) of three centers in one metropolitan and two urban areas of Italy.. Daily dietary intake was assessed using a 3-day diet diary in 128 HDP.. Mean daily intakes of trace elements were as follows: zinc, 7.6 ± 5.4 mg; copper, 14.3 ± 11.8 mg; selenium, 28.3 ± 18.1 μg; and iron, 7.2 ± 4.1 mg (7.8 ± 2.6 mg in women, 6.9 ± 2.4 mg in men). The distribution of patients by daily intakes of trace elements showed most were under the recommended values, with the exception of copper intake, which was much higher. Mean daily intakes of minerals were as follows: magnesium, 174.4 ± 94.3 mg; phosphorus, 842.6 ± 576.8 mg; calcium, 371.8 ± 363.7 mg; potassium, 1,616.2 ± 897.3 mg; and sodium, 1,350 ± 1,281 mg. Mean daily intakes of vitamins were as follows: vitamin A, 486.1 ± 544.6 μg; vitamin B1, 0.86 ± 0.7 mg; vitamin B2, 1.1 ± 0.7 mg; vitamin B3, 13.3 ± 8.1 mg; vitamin C, 47.8 ± 50.3 mg; and vitamin E, 9.5 ± 3.6 mg. The distribution of patients by daily intakes of vitamins showed most were under the recommended values. Daily intakes of trace elements and vitamins were similar among the three centers and did not differ between dialysis and non-dialysis days.. Many HDP have daily dietary intakes of trace elements and vitamins below the recommended values, whereas the intake of copper is much higher.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Calcium; Copper; Diet Records; Female; Food; Humans; Iron; Kidney Failure, Chronic; Magnesium; Male; Middle Aged; Minerals; Phosphorus; Potassium; Renal Dialysis; Sodium; Trace Elements; Vitamin A; Vitamin B Complex; Vitamin E; Vitamins; Zinc

Chronic renal failure patients undergoing peritoneal dialysis (PD) are characterized by increased oxidative stress (OS), which is associated with enhanced cardiovascular risk. Moreover, oxidative stress also contributes to peritoneal membrane changes and ultrafiltration failure. The aim of this study was to evaluate OS in PD patients and the effect of treatment with ascorbic acid and α-tocopherol.. Plasma, erythrocyte, urine, and peritoneal effluent samples from 20 patients on PD were evaluated for glutathione peroxidase and superoxide dismutase activity, total antioxidant capacity (TAC) and malondialdehyde (MDA) levels, as well as protein carbonyl formation, before and after administration of vitamin C, alone or in combination with vitamin E, in comparison with 10 apparently healthy control individuals.. All studied markers showed enhanced OS in the PD group, compared to controls. The supplementation of vitamin C and E resulted in improvements of all the OS markers, as indicated by increased erythrocyte antioxidant enzymes activity and TAC levels, as well as decreased MDA concentration and carbonyl compound formation.. The oral supplementation of antioxidant vitamins C and E, in combination, can lead to decreased OS, thus providing a useful and cost-effective therapeutic option in PD patients.

Topics: Aged; Analysis of Variance; Ascorbic Acid; Cardiovascular Diseases; Case-Control Studies; Dietary Supplements; Female; Follow-Up Studies; Glutathione Peroxidase; Humans; Kidney Failure, Chronic; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Peritoneal Dialysis, Continuous Ambulatory; Reference Values; Retrospective Studies; Risk Assessment; Superoxide Dismutase; Treatment Outcome; Vitamin E

Chronic kidney disease (CKD) may affect excretion and metabolism of vitamins but data for dogs are limited. In this study, blood vitamin levels were investigated in 19 dogs with chronic renal failure. High performance liquid chromatography was used to quantify retinol, retinyl esters, tocopherol, thiamine, riboflavin, pyridoxal-5'-phosphate, ascorbic acid and 25-hydroxycholecalciferol concentrations, whereas cobalamin, folate, biotin and pantothenic acid were measured by microbiological methods. Levels of retinol, retinyl palmitate, ascorbic acid, and vitamins B1, B2 and B6 were increased compared to healthy dogs. Dogs with CKD showed decreased concentrations of 25-hydroxycholecalciferol and folate. Alpha-tocopherol, biotin, pantothenate and cobalamin levels were not significantly different between controls and dogs with CKD. Whether lower vitamin D and folate concentrations in dogs with CKD justify supplementation has to be evaluated in future studies.

Topics: Animals; Ascorbic Acid; Calcifediol; Case-Control Studies; Diterpenes; Dog Diseases; Dogs; Female; Folic Acid; Kidney Failure, Chronic; Male; Retinyl Esters; Riboflavin; Thiamine; Vitamin A; Vitamin B 6; Vitamins

We evaluated the relationship of the plasma copper/zinc (Cu/Zn) ratio with nutritional status, inflammation, oxidative stress, and immune function in peritoneal dialysis patients.. Clinical and laboratory parameters were measured in patients (n=45) and age- and sex-matched healthy individuals (n=30).. There were significant negative correlations of the Cu/Zn ratio with nutrition-related parameters (body mass index [BMI], creatinine, hemoglobin, and albumin) and antioxidant (vitamin C and E) levels and positive correlations of the Cu/Zn ratio with the levels of high sensitivity C-reactive protein (hs-CRP) and oxidation products (malondialdehyde [MDA] and protein carbonyl). The Cu/Zn ratio was negatively correlated with the percentages of B- and T-lymphocyte subsets and the ratio of CD4/CD8 antigens.. In peritoneal dialysis patients, elevated Cu/Zn ratios are associated with malnutrition, increased oxidative stress, inflammation, and disrupted immune status.

Topics: Albumins; Ascorbic Acid; B-Lymphocyte Subsets; Biomarkers; Body Mass Index; C-Reactive Protein; Case-Control Studies; CD4-CD8 Ratio; Copper; Creatinine; Female; Hemoglobins; Humans; Immunity; Inflammation; Kidney Failure, Chronic; Male; Malondialdehyde; Middle Aged; Nutritional Status; Oxidative Stress; Peritoneal Dialysis; T-Lymphocyte Subsets; Taiwan; Vitamin E; Zinc

Subclinical inflammation is a common phenomenon in patients on either continuous ambulatory peritoneal dialysis (CAPD) or maintenance hemodialysis (MHD). We hypothesized that vitamin C had anti-inflammation effect because of its electron offering ability. The current study was designed to test the relationship of plasma vitamin C level and some inflammatory markers.. In this cross-sectional study, 284 dialysis patients were recruited, including 117 MHD and 167 CAPD patients. The demographics were recorded. Plasma vitamin C was measured by high-performance liquid chromatography. And we also measured body mass index (BMI, calculated as weight/height(2)), Kt/V, serum albumin, serum prealbumin, high-sensitivity C-reactive protein (hsCRP), ferritin, hemoglobin. The relationships between vitamin C and albumin, pre-albumin and hsCRP levels were tested by Spearman correlation analysis and multiple regression analysis. Patients were classified into three subgroups by vitamin C level according to previous recommendation 12 in MHD and CAPD patients respectively: group A: < 2 ug/ml (< 11.4 umol/l, deficiency), group B: 2-4 ug/ml (11.4-22.8 umol/l, insufficiency) and group C: > 4 ug/ml (> 22.8 umol/l, normal and above).. Patients showed a widely distribution of plasma vitamin C levels in the total 284 dialysis patients. Vitamin C deficiency (< 2 ug/ml) was present in 95(33.45%) and insufficiency (2-4 ug/ml) in 88(30.99%). 73(25.70%) patients had plasma vitamin C levels within normal range (4-14 ug/ml) and 28(9.86%) at higher than normal levels (> 14 ug/ml). The similar proportion of different vitamin C levels was found in both MHD and CAPD groups. Plasma vitamin C level was inversely associated with hsCRP concentration (Spearman r = -0.201, P = 0.001) and positively associated with prealbumin (Spearman r = 0.268, P < 0.001), albumin levels (Spearman r = 0.161, P = 0.007). In multiple linear regression analysis, plasma vitamin C level was inversely associated with log(10)hsCRP (P = 0.048) and positively with prealbumin levels (P = 0.002) adjusted for gender, age, diabetes, modality of dialysis and some other confounding effects.. The investigation indicates that vitamin C deficiency is common in both MHD patients and CAPD patients. Plasma vitamin C level is positively associated with serum prealbumin level and negatively associated with hsCRP level in both groups. Vitamin C deficiency may play an important role in the increased inflammatory status in dialysis patients. Further studies are needed to determine whether inflammatory status in dialysis patients can be improved by using vitamin C supplements.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; C-Reactive Protein; Comorbidity; Cross-Sectional Studies; Female; Humans; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Peritoneal Dialysis; Prealbumin; Prevalence; Renal Dialysis; Severity of Illness Index

In end-stage renal disease, there is a high incidence of secondary hyperparathyroidism. It is proposed that increasing vitamin C levels by dietary supplementation results in a decrease of parathyroid hormone (PTH) in vitamin C-deficient hemodialysis patients with secondary hyperparathyroidism. The aim of this study was the evaluation of vitamin C administration for reduction of serum PTH level in hemodialysis patients.. Twenty-one hemodialysis patients with serum PTH levels less than 550 pg/mL (but more than 200 pg/mL) were administered intravenous vitamin C, 200 mg, 3 times per week for 3 months. Blood samples for measurement of PTH were obtained at the beginning of the hemodialysis session every month for three months.. The mean level of serum biointact PTH was 333.3 ± 141.3 pg/mL (reference range, 7 pg/mL to 82 pg/mL) at baseline, and it decreased to 256.5 ± 137.2 pg/mL at 1 month (P = .03). The mean PTH level was also lower than the baseline value at 2 months (260.1 ± 123.2 pg/mL, P = .03), while it increased to 328.9 ± 176.0 pg/mL at 3 months, which was still slightly lower than the baseline level (P = .13). In 15 patients (71.4%), serum levels of PTH were lower than the baseline at months 1 to 2, while in the remaining 6 (28.6%), it was higher than the baseline value. At 3 months, 5 of the 15 patients with lower PTH levels up to the 3rd month experienced an increase in these levels again.. Administration of intravenous vitamin C in hemodialysis patients noticeably decreased level of PTH, but its effect gradually diminished.

Topics: Adult; Ascorbic Acid; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Hyperparathyroidism, Secondary; Injections, Intravenous; Kidney Failure, Chronic; Male; Parathyroid Hormone; Renal Dialysis; Retrospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome; Vitamins

Some studies have hypothesized the protective role of vitamin C against cardiovascular disorders (CVD) in patients with end-stage renal disease (ESRD). This study was designed to assess plasma vitamin C concentration and its relationship to hemodialysis (HD) patients' morbidity and mortality.. Plasma vitamin C concentrations were assessed in HD patients using spectrophotometry and subjects were prospectively followed for up eighteen months for all-cause mortality. Any association between vitamin C concentration and patients' demographic data, co-morbidities, or the cause of ESRD were investigated using the Chi-square test.. Ninety-one patients with a mean age of 56.7 ± 15.7 years were included in this study. The most frequent cause of ESRD was simultaneous hypertension and diabetes in 30 % of patients, followed by hypertension in 25.6 %, and diabetes in 11.1 %, respectively. About 34 % of patients had CVD as the most prevalent co-morbidity. Forty-nine patients (53.8 %) had low levels of vitamin C concentration. There was a significant relationship between vitamin C insufficiency and presence of any co-morbidity in HD patients (p < 0.05). There was a significant difference in vitamin C concentrations between patients without co-morbidities and those with cardiovascular ones (F[2,88]=3.447, p = 0.036). Twenty-two (24.2 %) patients died over a median duration of 227 days. There was a significant difference in time to death of patients with and without low levels of vitamin C concentration (p = 0.04).. The results showed lower plasma vitamin C levels in HD patients who suffered any co-morbidity and sooner time to death in these patients.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Diabetic Nephropathies; Female; Follow-Up Studies; Hospitals, University; Humans; Hypertension; Iran; Kidney Failure, Chronic; Male; Middle Aged; Morbidity; Mortality; Prospective Studies; Renal Dialysis; Survival Analysis; Young Adult

Patients on conventional hemodialysis (HD) have elevated markers of oxidative stress and chronic inflammation, which may contribute to a high prevalence of cardiovascular disease. Glutathione (GSH), an important intracellular antioxidant, requires cysteine as a rate-limiting amino acid for its synthesis and riboflavin for its regeneration.. We aimed to examine whether erythrocyte GSH (eGSH) concentrations and riboflavin status are influenced by the increased dialysis dose provided to vitamin-supplemented patients receiving home nocturnal hemodialysis (HNHD) (6-8 hours/session, 5-7 nights/week) compared with patients on standard hemodialysis (SHD) (4 hours/session, 3 days/week).. This was a cross-sectional comparative study involving 30 patients undergoing SHD or HNHD regimens and a group of 15 healthy control subjects (HC). We measured eGSH concentration by liquid chromatography-tandem mass spectrometry, riboflavin status by eGSH reductase activity coefficient (EGRAC) as well as plasma total cysteine (Cys) and total homocysteine (Hcy), vitamin C by high-performance liquid chromatography, and C-reactive protein (CRP) by standard method. Estimated dietary protein and energy intakes were determined by 3-day food records, and nutritional status was assessed by subjective global assessment (SGA).. There were no significant differences among groups in eGSH concentration, EGRAC, dietary protein intake, and SGA score. SHD patients had significantly higher plasma Cys (P < .001) and Hcy compared with HNHD and HC groups (P = .048). Vitamin C was significantly lower (P = .01) and CRP significantly higher (P = .048) in both HD groups compared with HC.. eGSH concentration appears to be unaffected by dialysis dose in well-nourished HD patients.

Topics: Adult; Ascorbic Acid; C-Reactive Protein; Cross-Sectional Studies; Cysteine; Dietary Proteins; Energy Intake; Erythrocytes; Female; Glutathione; Glutathione Reductase; Hemodialysis, Home; Homocysteine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nutritional Status; Renal Dialysis; Riboflavin; Vitamins

To examine the serum antioxidant levels like vit-C, vit-E and glutathione in patients with renal diseases who were subjected to dialysis and to evaluate the antioxidant by FRAP method. To find out the involvement of free radicals in pathogenesis of renal disease. Fifty patients with high levels of creatinine and urea level were included in the study of dialysis. A difference of antioxidant level of vit-C, vit-E and glutathione was observed. The study therefore suggests the importance of assessing these marker oxidative stress antioxidant capacities in renal disease during dialysis.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Blood Chemical Analysis; Creatinine; Glutathione; Humans; Kidney Failure, Chronic; Middle Aged; Oxidative Stress; Renal Dialysis; Urea; Vitamin E

Although hemodialysis (HD) is essential for end-stage renal disease patients, at the same time it causes oxidative stress and long-term pro-atherosclerotic effects. This study aimed to determine lipid profile as well as the total antioxidant capacity (TAC) and vitamins A, E, and C in HD patients. The study enrolled 31 patients (50.3 ± 14.9 years old) undergoing maintenance 4-hour HD three times per week with a polysulfone membrane dialyzer for a mean of 76.1 months (range, 7-120 months) and 31 healthy individuals (47.8 ± 13.9 years old). Lipid profiles were determined spectrophotometrically using commercially available kits. Total antioxidant capacity was determined by ferric reducing/antioxidant power assay, levels of vitamins A and E were assayed using high-pressure liquid chromatography, and the level of vitamin C was measured by a photometric method. Our results showed that before HD, the levels of TAC and vitamin A were significantly higher than in normal subjects, whereas the levels of high-density lipoprotein (HDL) and vitamin C were lower than in control subjects (P < .001). There was no significant difference between normal subjects and patients before dialysis regarding low-density lipoprotein (LDL) and vitamin E levels (P > .05). After HD, the levels of HDL-cholesterol, vitamins E and C, and TAC decreased significantly (P < .001), but the decreased level of vitamin A still remained higher than controls (P < .05), whereas the levels of LDL were significantly higher than controls (P < .001). In conclusion, alterations in the lipoprotein profiles and antioxidant markers following HD suggest an increased risk of atherosclerosis in these patients.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Atherosclerosis; Female; Humans; Kidney Failure, Chronic; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Reproducibility of Results; Vitamin A; Vitamin E

To determine the efficacy and effects of the oral administration of ascorbic acid on anemia management in ESRD patients with hyperferritinemia.. Twenty-one anemic hemodialysis patients with ferritin levels greater than 350 ng/mL had received oral daily ascorbic acid at a dose of 500 mg/day and were retrospectively studied. Hemoglobin, hematocrit, EPO dose, ferritin, and transferrin saturation were recorded at baseline and after three months of treatment. EPO dose/hematocrit was calculated. Serum oxalate levels were also measured.. Hb increased 9% from 11.4 to 12.2 gm/dL (p = 0.05), HCT increased 10% from 33.3 to 36.7% (p = 0.05), but EPO dose requirement decreased 33% from 26,229 to 17,559 U/week (p = 0.03). Ferritin levels decreased 21% from 873 to 691 ng/mL (p = 0.004). Mean oxalate level during therapy was 87 micromol/L (normal <27). Patients with oxalate levels >27 micromol/L were instructed to stop ascorbic acid treatment, and mean levels decreased from 107 to 19 micromol/L (p = 0.01) over a mean time of 71 days.. In this study, daily oral ascorbic therapy decreased ferritin levels and EPO dose requirements while raising hemoglobin and hematocrit level. This beneficial profile of effects of ascorbic acid therapy is consistent with improvement of EPO resistance and cost savings in this population.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anemia; Ascorbic Acid; Cohort Studies; Drug Administration Schedule; Female; Ferritins; Humans; Iron Metabolism Disorders; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Treatment Outcome; Vitamins

Oxalic acid (OA) is thought to be a uremic toxin that participates in the pathogenesis of uremic syndrome. The objectives of this study were to: (1) evaluate the plasma levels of OA in patients with chronic renal disease with various levels of glomerular filtration rate and after renal transplantation; (2) investigate the salivary secretion of OA and ascorbic acid in healthy subjects and in patients with chronic renal failure (CRF); (3) examine the influence of water and sodium diuresis and furosemide administration on the urinary excretion of OA and ascorbic acid in healthy subjects and in CRF patients without dialysis treatment; and (4) evaluate the influence of renal replacement therapy (RRT) on secondary hyperoxalemia in hemodialysis patients.. This study was conducted at the Nephrological Department of P.J. Safárik University. Sixty-one patients with chronic renal disease, 64 CRF patients, 32 continuous ambulatory peritoneal dialysis (CAPD) patients, 15 hemodialysis patients, 21 patients after renal transplantation, and 15 healthy subjects were examined. Maximal water diuresis, diets with low (2 g/day) and high (15 g/day) sodium intake, administration of intravenous furosemide (20 mg), and renal replacement therapy (CAPD, hemodialysis, hemofiltration, and postdilution hemodiafiltration) were utilized in the study.. In patients with chronic renal disease and those after renal transplantation, direct relationships between plasma OA and serum creatinine were found (r = 0.904 and 0.9431, respectively, P < .01). Despite a high level of plasma OA in uremic patients (23.1 +/- 10 micromol/L), there was no significant difference in salivary OA between control subjects (128 +/- 19 micromol/L) and CRF patients (135 +/- 24 micromol/L). The urinary excretion of OA during maximal water diuresis (from 37.5 to 110.3 micromol/4 hours) and after intravenous furosemide (from 34.5 to 66.7 micromol/3 hours) increased significantly, but was not affected by high intake of NaCl. The most significant decrease of plasma OA was observed during postdilution hemodiafiltration (63.3%).. Our study indicates that renal replacement therapy is not effective for a permanent reduction of elevated plasma levels of OA.

Topics: Adult; Ascorbic Acid; Atherosclerosis; Creatinine; Female; Glomerulonephritis; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Uremia; Vitamin B 6

Renal failure is associated with several metabolic disturbances and increasing evidences support a role of oxidative stress and impaired antioxidant defence in the pathologic mechanisms that may contribute to accelerated atherogenesis in these patients. Aim of the study was to further investigate the relationship between oxidative stress and chronic renal failure.. We compared the paraoxonase (PON1) activity, the levels of lipid hydroperoxides and AGE adducts in plasma of hemodialysis patients before and after intravenous administration of vitamin C.. An increase in lipid hydroperoxides, AGE adducts and a decrease in the activity of PON1 were observed in patients with respect to controls. The comparison before and after supplementation with vitamin C showed an increase of PON1 activity and a decrease of AGE and lipid hydroperoxides levels.. The results provide further evidence that lipid peroxidation and impairment of antioxidant system in plasma of patients may play a role in renal disease and suggest that evaluation of PON1 activity could represents an useful approach to monitor antioxidant treatment and new dialysis therapies.

Topics: Aged; Antioxidants; Aryldialkylphosphatase; Ascorbic Acid; Dietary Supplements; Female; Glycation End Products, Advanced; Humans; Kidney Failure, Chronic; Lipid Peroxidation; Lipid Peroxides; Male; Middle Aged; Oxidative Stress; Renal Dialysis

An adequate total body pool of ascorbate is essential for optimum health in humans. Requirements for ascorbate are increased in peritoneal dialysis (PD) patients most likely due to a combination of poor nutrition and increased dialysate losses.. We measured serum ascorbate levels in 45 clinically stable PD patients to assess the prevalence of ascorbate insufficiency (level between 2 and 4 mg/L) and deficiency (level <2 mg/L). We also assessed the efficacy of subsequent supplementation and patients' adherence to the prescribed supplementation. All patients were advised on commencement of dialysis to take a multivitamin tablet containing 100-120 mg ascorbate.. Eighteen (41%) PD patients were regularly taking ascorbate-containing multivitamins, while 27 (59%) patients did not take ascorbate supplements. Serum ascorbate levels ranged from <0.2 to 41 mg/L, with wide variations in serum ascorbate at any given intake level. Ascorbate deficiency was present in 1/3 of the current PD population (44% of patients not taking supplements and in 16% of those on supplements), although none of the patients demonstrated clinical manifestations of scurvy. Targeted supplementation of ascorbate insufficient patients increased the median serum ascorbate level from 1.7 mg/L (IQR 1.2-2.2) to 22.5 mg/L (IQR 16.7-32.9).. Our results show that, in PD patients, ascorbate deficiency is common and can readily be identified with serum ascorbate measurements. Oral supplements in the form of inexpensive multivitamin preparations restore adequate serum ascorbate levels in the majority of these patients. We therefore suggest measurement of ascorbate levels in all PD patients at the commencement of dialysis with a target level in the normal range (4-14 mg/L).

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Prevalence

50 Patients with chronic renal failure undergoing hemodialysis with or without porphyria cutanea tarda (PCT)-like skin changes were investigated. The total porphyrin amount in erythrocytes, plasma and dialysate and the distribution of porphyrin metabolites in plasma and dialysate were measured. In plasma, the group of patients with skin changes (referred as PCU = porphyria cutanea uremica) showed significantly increased uroporphyrin levels as compared to the non-symptomatic group. In addition, significant differences concerning the ratio uro-/coproporphyrin in plasma were shown: non-symptomatic patients with 0.87, as opposed to the PCU group with 3.7. Considerable differences between the level of vitamin ingestion were identified between the groups. Patients with PCU took distinctly less vitamins C, E and B than patients without symptoms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Coproporphyrins; Dose-Response Relationship, Drug; Female; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Porphyria Cutanea Tarda; Reference Values; Renal Dialysis; Risk Factors; Uremia; Uroporphyrins; Vitamin B Complex; Vitamin E; Vitamins

Increased lipid peroxidation (LP) and reduced enzymatic antioxidant defense have been observed in predialysis patients with advanced chronic renal failure (CRF) and in patients on maintenance hemodialysis (HD). To extend these observations, we evaluated the plasma, erythrocyte and dialysate levels of vitamins A and E and the plasma and dialysate levels of vitamin C as exogenous non-enzymatic antioxidants in children with CRF treated conservatively and on HD. The data obtained were related to LP monitored by erythrocyte malonyldialdehyde (E-MDA) and plasma organic hydroperoxide (OHP) concentrations.. Forty-six predialysis children were enrolled in the study and divided into 2 groups: group I = moderate CRF (plasma creatinine < 265.3 micromol/l), and group II = plasma creatinine > or = 265.3 micromol/l. Group III consisted of 21 HD children. 27 age-matched healthy subjects served as a control group.. The plasma levels of vitamin A and vitamin C were significantly reduced in all CRF patients when compared to the controls, with the lowest values observed in children on maintenance HD (group III). Significant differences were also noted between the moderate CRF (group I) and HD (group III). Plasma levels of vitamin E were significantly decreased in moderate CRF (group I) and HD (group III) as compared to controls. In contrast, the erythrocyte vitamin A and vitamin E levels of predialysis children and HD patients were not different from the controls. The E-MDA and OHP concentrations in the 3 groups of CRF children were significantly higher than in healthy subjects. The concentration of plasma vitamin C was significantly inversely correlated with E-MDA, plasma OHP and creatinine in group I. In group II we found a significant correlation of plasma vitamin E levels with creatinine and E-MDA and a correlation of the plasma vitamin C concentration with E-MDA.. CRF in children is associated with decreased concentrations of plasma antioxidant vitamins. This reduction is most expressed in children on maintenance HD and particularly concerns plasma vitamin C and erythrocyte vitamin E concentrations. The low levels of plasma vitamin A, E and C might result in reduced activity of the non-enzymatic antioxidant defense system and might be responsible for increased oxidative stress occurring in children with CRF.

Topics: Adolescent; Antioxidants; Ascorbic Acid; Child; Female; Humans; Kidney Failure, Chronic; Lipid Peroxidation; Male; Vitamin A; Vitamin E; Vitamins

Topics: Antioxidants; Ascorbic Acid; Atherosclerosis; Ferritins; Hemoglobins; Humans; Inflammation; Iron; Kidney Failure, Chronic; Oxidants; Oxidative Stress; Renal Dialysis

Topics: Anemia; Ascorbic Acid; Chemotherapy, Adjuvant; Clinical Trials as Topic; Drug Therapy, Combination; Erythropoietin; Humans; Kidney Failure, Chronic

Accumulation of advanced glycation end-products (AGEs) has been implicated in the pathogenesis of chronic transplant dysfunction and cardiovascular disease in renal transplant recipients. We aimed to investigate which factors are associated with tissue AGE accumulation in renal transplant recipients.. The AGE accumulation was assessed using a validated skin-autofluorescence reader (AFR) in 285 consecutive renal transplant recipients (57% male, aged 50+/-12 years) visiting the outpatient clinic at a median (interquartile range) time of 73 (32-143) months after transplantation. Furthermore, various transplant- and recipient-related factors of interest were collected.. Average skin-autofluorescence of lower arm and leg was 2.7+/-0.8 a.u. Skin-autofluorescence was positively determined by recipient age, systolic blood pressure, smoking, high-sensitivity C-reactive protein, duration of pre-transplant dialysis, and negatively by plasma vitamin C levels, creatinine clearance at baseline, and change in creatinine clearance since one year after transplantation in linear multivariate regression analysis. Together, these factors explained 41% of the variance of skin-autofluorescence.. Skin-autofluorescence was associated with several risk factors for cardiovascular disease and chronic renal transplant dysfunction. These results are in line with the hypothesis that AGEs play a role in the pathogenesis of these conditions in renal transplant recipients. Prospective studies are required to investigate whether the AFR can be used as a simple, non-invasive tool to identify and monitor patients at risk for chronic renal transplant dysfunction and cardiovascular disease.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Ascorbic Acid; C-Reactive Protein; Cardiovascular Diseases; Comorbidity; Creatinine; Delayed Graft Function; Diabetes Complications; Female; Fluorometry; Forearm; Glycated Hemoglobin; Glycation End Products, Advanced; Histocompatibility; Humans; Hypercholesterolemia; Hypertension; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Leg; Linear Models; Male; Middle Aged; Obesity; Risk Factors; Skin; Smoking; Vitamin E

Hemodialysis patients are prone to deficiency of vitamin C, which constitutes the most abundant nonenzymatic antioxidant in blood. Because antioxidants are involved in the pathogenesis of atherosclerosis, the authors examined the association of total vitamin C plasma level with cardiovascular outcomes in such patients. One hundred thirty-eight consecutive maintenance hemodialysis patients (median age 61 yr, 90 males) were enrolled in a single-center study. At baseline, routine laboratory parameters were recorded, and predialysis total vitamin C plasma levels were measured by high-pressure liquid chromatography. Patients were prospectively followed-up for the occurrence of a primary composite endpoint consisting of fatal and nonfatal major adverse cardiovascular events (MACE) and for all-cause and cardiovascular mortality. MACE occurred in 35 patients (25%) over a period of median 30 mo, and 42 patients (30%) died [29 cardiovascular deaths (21% of total)]. Using Cox proportional hazards modeling, adjusted hazard ratios for the occurrence of MACE were 3.90 (95% confidence interval [CI]: 1.42 to 10.67; P = 0.008) and 3.03 (95% CI: 1.03 to 8.92; P = 0.044) for patients in the lower (<32 micromol/L) and middle (32 to 60 micromol/L) tertile of total vitamin C levels, compared with patients in the upper tertile (>60 micromol/L). Hazard ratios for cardiovascular death were 3.79 (95% CI: 1.23 to 11.66; P = 0.020) and 2.89 (95% CI: 0.89 to 9.37; P = 0.076). Total vitamin C levels were not independently associated with all-cause mortality. This study concludes that low total vitamin C plasma levels predict adverse cardiovascular outcomes among maintenance hemodialysis patients. Future studies should address the potential protective effect of an adequate vitamin C supplementation.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Risk Factors

Topics: Anemia; Antioxidants; Ascorbic Acid; Drug Therapy, Combination; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Injections, Intravenous; Kidney Failure, Chronic; Renal Dialysis

Intravenous vitamin C supplementation to haemodialysis patients might ameliorate responsiveness to recombinant human erythropoietin (rHuEpo). This study was performed to analyse the relation between vitamin C plasma concentration and response to rHuEpo.. In a cross-sectional, single-centre observational study including all haemodialysis patients, pre-dialysis plasma vitamin C concentrations were measured by high-performance liquid chromatography and response to rHuEpo (haemoglobin concentration/international units rHuEpo/kg/week) was recorded together with baseline laboratory data.. Univariate analysis yielded a significant correlation between vitamin C plasma levels and response to rHuEpo (n = 130, r = 0.25, P = 0.004), which still persisted after adjustment for transferrin saturation, C-reactive protein, malondialdehyde, parathyroid hormone, route of rHuEpo administration, residual renal function and diabetes mellitus (adjusted r = 0.23, P = 0.014). Analysis per quartiles of vitamin C plasma level revealed a significantly lower response to rHuEpo with decreasing vitamin C values (P = 0.026).. In unselected haemodialysis patients, vitamin C plasma levels account, at least partially, for the response to rHuEpo. Larger-sized interventional studies are needed to find out whether vitamin C plasma levels may or may not appropriately reflect the potential beneficial effect of vitamin C supplements on rHuEpo responsiveness.

Topics: Aged; Anemia; Ascorbic Acid; Cross-Sectional Studies; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Ascorbic acid overload and vitamin B6 deficiency have been implicated in the development of hyperoxalemia in dialysis patients, but there is still disagreement about this. Hemodialysis patients who are exposed long-term hyperoxalemia may develop secondary oxalosis with an increased risk of cardiac, vascular, and bone disease, and thus may benefit from maintaining a low serum oxalic acid level. In 452 hemodialysis patients, the serum level of oxalic acid was 47.2 +/- 22.9 micromol /l before and 16.9 +/- 10.5 micromol/l after a 4-hour dialysis session, while the ascorbic acid levels were 39.0 +/- 92.7 micromol/l and 6.5 +/- 18.6 micromol/l, the glycolic acid levels were 7.3 +/- 10.1 micromol/l and 0.6 +/- 2.3 micromol/l, and the citric acid levels were 141.3 +/- 54.7 micromol/l and 117.6 +/- 37.2 micromol/l, respectively. Most patients (65.3 percent) had low serum ascorbic acid levels (less than 10 micromol/l) before hemodialysis. The serum level of oxalic acid [Ox] showed a significant positive correlation with the levels of ascorbic acid [AA], glycolic acid [Gly], and creatinine [Cre]: [Ox] = 21.711 + 0.181 x [AA] + 0.174 x [Gly] + 0.171 x [Cre], (all micromol/l, p less than 0.05). In 124 dialysis patients, the 4-pyridoxic acid level was 8.9 +/- 19.6 micromol /l before and 3.9 +/- 8.8 micromol/l after dialysis, and it was not correlated with oxalic acid or glycolic acid. Most dialysis patients (65.3 percent) had low serum levels of ascorbic acid, but a subgroup of patients (12 percent) had high serum ascorbic acid levels (more than 100 micromol/l) associated with hyperoxalemia (88.2 +/- 24.5 micromol/l). High-dose vitamin C supplementation may aggravate hyperoxalemia in hemodialysis patients, so attention should be paid to avoiding this risk.

Topics: Aged; Ascorbic Acid; Citric Acid; Creatinine; Female; Glycolates; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalic Acid; Pyridoxic Acid; Renal Dialysis; Risk; Time Factors; Vitamin B 6

The status of ascorbic acid (AA) in dialysis patients is the subject of debate. Some reports have found AA to be deficient in dialysis patients, while others have found that AA is not deficient. In an attempt to confirm AA serum concentrations in dialysis patients, we analyzed the concentrations of AA as well as its metabolites using the specific determination of AA with chemical derivatization and the HPLC method. We studied 131 patients under maintenance hemodialysis therapy (HD), 23 patients with chronic renal failure (CRF) and 48 healthy controls (C). Serum concentrations of AA and the AA metabolites dehydroascorbic acid (DHA) and 2, 3-diketogulonate (DKG) were measured by HPLC. Nine HD patients were taking AA supplements. Seventy-six (62.3%) of the 122 HD patients not taking AA supplements exhibited deficient levels of AA (< 20 microM), while 13 (56.5%) of the 23 CRF patients and 9 (18.8%) of the 48 C showed deficient levels of AA. Analysis of AA metabolites in the normal-range AA (20-80 microM) group revealed that the DHA/AA ratio in HD patients was significantly higher than in C (3.3 +/- 2.6% and 1.2 +/- 2.2%, respectively). The DKG/AA ratio in HD patients was higher than in CRF patients (3.6 +/- 5.2% vs. 0.9 +/- 1.9%), whereas DKG was not detected in C. When compared to serum levels before the start of dialysis, serum AA, DHA and DKG concentrations at the end of the dialysis session decreased by an average of 74.2, 84.0 and 78.8% respectively. In HD patients, serum levels of thiobarbituric reactive substances (TBARS) were significantly lower in the higher AA (> 80 microM) group than in the deficient and normal-range AA groups. In 12 AA-deficient patients, after 1 month of taking AA supplements (200 mg/day), serum AA levels rose to 79.9 microM, while serum TBARS level declined when compared with levels before supplementation. In conclusion, the frequency of AA deficiency in dialysis patients is extremely high. AA deficiency in HD patients may result in high TBARS levels, which reflect increased oxidative stress. Adequate AA supplementation should therefore be considered in such patients.

Topics: 2,3-Diketogulonic Acid; Administration, Oral; Aged; Aorta; Ascorbic Acid; Ascorbic Acid Deficiency; Calcinosis; Calcium Oxalate; Chromatography, High Pressure Liquid; Dehydroascorbic Acid; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Thiobarbituric Acid Reactive Substances

The effect of intravenous ascorbic acid was compared with that of intravenous iron in the treatment of functional iron deficiency, as defined as serum ferritin levels over 300 ng/ml and serum iron levels below 50 microg/dl, in patients on chronic hemodialysis. Thirteen patients on chronic hemodialysis with functional iron deficiency received intravenous injections of ascorbic acid, 100 mg, three times a week, after hemodialysis. The therapy was continued until serum ferritin decreased to below 300 ng/ml (3 months at the maximum). The iron and control group were composed of patients who had serum iron levels below 50 microg/dl within 3 months after serum ferritin rose to over 300 ng/ml. Seven patients with the iron group received more than a total of 10 intravenous injections of saccharated ferric oxide (40 mg/dose) after hemodialysis, and seven patients with the control group received no iron preparation during the 3 months. In the ascorbic acid group, while hemoglobin did not change from 10.9 +/- 0.5 g/dl (mean +/- SE) during the three-month period, serum iron increased significantly from 37 +/- 4 microg/dl to 49 +/- 4 microg/dl after one month (p<0.01), and remained elevated until the end of the three-month period. Serum ferritin decreased significantly from 607 +/- 118 ng/ml to 354 +/- 30 ng/ml after 3 months (p<0.01). In the iron group, hemoglobin and serum iron increased significantly from the respective pre-treatment levels during the 2-month period, and serum ferritin rose significantly after 3 months. In the control group, hemoglobin, serum iron and ferritin levels decreased significantly from the respective pre-treatment levels during the 3 months. The recombinant erythropoietin dose remained stable for three months in the ascorbic acid, iron, and control groups, respectively. These results suggest that in hemodialysis patients with a functional iron deficiency, treatment with intravenous ascorbic acid can prevent iron overload due to treatment with intravenous iron, and provide a useful adjuvant means of maintaining hemoglobin and serum iron levels.

Topics: Aged; Anemia, Iron-Deficiency; Ascorbic Acid; Biomarkers; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Treatment Outcome

Recent report demonstrates that inadequate iron mobilization and defective iron utilization may cause recombinant erythropoieitin (rEPO) hyporesponsiveness in hemodialysis (HD) patients with iron overload. The effect of intravenous ascorbic acid (IVAA) in HD patients selected on the basis of iron overload and EPO resistance also has been proven. However, it is uncertain whether IVAA still works in diabetic ESRD patients with hyperferritinemia. Therefore, the aim of this study focusing on diabetic ESRD patients was to analyze the potential effect of low dose IVAA on improvement of anemia and erythropoiesis-related parameters when compared with control period.. This study consisted of 22 chronic hemodialysis patients with type II diabetes in a single dialysis unit. In studies of this type, all eligible patients are followed up, but the primary comparison is still between different sequentially treatment including control period and post-IVAA period in same patients. IVAA patients received ascorbic acid, 100 mg each administered intravenously three times per week for eight weeks of treatment and four months of post-treatment follow-up.. The demographic characteristics of 22 diabetic uremic patients show that mean age is 63.6 +/- 10.2 years old. The ratio of sex (M/F) = 10/12. Mean duration of HD is 46.7 +/- 33.2 months. As for the urea kinetic study between these two periods including KT/V, nPCR, and URR, there is no significantly different. As for anemia-related parameters, Hb and Hct increased significantly in post-IVAA period after 3 months compared with control period, while MCV did not increase significantly. Serum ferritin significantly decreased at study completion. The same situation is for iron. As for TS, it significantly increased at one month and further markedly increased at subsequent three months.. This study has demonstrated that short-term low dose IVAA therapy can facilitate iron release from reticuloendothelial system but also increase iron utilization in diabetic hemodialysis patients with iron overload. Therefore, IVAA is a potential adjuvant therapy to treat erythropoeitin-hyporesponsive anemia in iron-overloaded patients.

Topics: Aged; Anemia; Ascorbic Acid; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dose-Response Relationship, Drug; Erythrocyte Indices; Erythropoietin; Female; Ferritins; Follow-Up Studies; Free Radical Scavengers; Hematocrit; Hemoglobins; Humans; Infusions, Intravenous; Iron; Iron Overload; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Phosphates; Prospective Studies; Recombinant Proteins; Renal Dialysis; Serum Albumin; Taiwan; Time Factors; Treatment Outcome

Dysfunctional endothelium caused by oxidative stress is thought to play a role in pathogenesis of a variety of conditions including atherosclerosis. We investigated whether a microcirculatory disturbance in hemodialysis (HD) patients was associated with increased oxidative stress and endothelial injury.. Transcutaneous oxygen tension (TcPO2) on the dorsum of the foot at rest was measured as a marker of microcirculation in 33 patients undergoing HD without clinical manifestations of peripheral arterial disease and 20 healthy controls. Furthermore, in order to examine whether TcPO2 was affected by antioxidants, oral supplementation with a combination of vitamin C (200 mg daily) and vitamin E (600 mg daily) was administered for 6 months to 8 patients with microcirculatory disturbance (TcPO2 values of 50 mmHg or less). Serum biochemical parameters including vitamins were also measured.. Mean TcPO2 value was significantly lower in HD patients than in control subjects (47.9 +/- 13.5 mmHg versus 62.4 +/- 11.9 mmHg, p < 0.001). After vitamin supplementation, TcPO2 values remarkably increased (40.6 +/- 10.0 mmHg versus 57.4 +/- 6.5 mmHg, p < 0.005). Serum vitamin C and vitamin E levels increased significantly as well, while serum levels of thrombomodulin, a marker of endothelial injury, and thiobarbituric acid reactants, a marker of lipid peroxidation, were significantly decreased in comparison with those before supplementation.. Our results suggest that the microcirculatory disturbance in HD patients seems to be associated with endothelial damage caused by oxidative stress. Combined supplementation with vitamin C and vitamin E may be of clinical benefit in improving the cutaneous microcirculation by reducing oxidative stress.

Topics: Antioxidants; Ascorbic Acid; Blood Gas Monitoring, Transcutaneous; Endothelium, Vascular; Female; Foot; Humans; Kidney Failure, Chronic; Lipid Peroxidation; Male; Microcirculation; Middle Aged; Oxidative Stress; Peripheral Vascular Diseases; Renal Dialysis; Skin; Thiobarbituric Acid Reactive Substances; Thrombomodulin; Vitamin E

An increased apoptotic rate of peripheral blood mononuclear leukocytes (PBMLs) in haemodialysis (HD) patients has been reported in several studies, but its underlying mechanisms remain poorly understood. Oxidant stress is a well known cause of cell damage, and several lines of evidence suggest that it might influence the induction and signalling steps of mononuclear cell apoptosis through different mechanisms so as to provoke disturbances of the intracellular pool of thiols (SHi). In this study, we investigated the in vitro apoptotic rate and SHi of PBMLs in end-stage renal disease (ESRD) patients on HD or peritoneal dialysis (PD).. Apoptosis and SHi were evaluated in vitro in PBMLs obtained from 40 ESRD patients (HD, n = 30 and PD, n = 10) and 10 healthy controls. A subgroup of HD patients was also studied before and after 1 month of treatment with a vitamin E-coated dialyser (CL-E). Cell thiols and viability were also assessed in the monocyte-like cell line U937 and PBMLs after incubation in the presence of uraemic plasma with or without supplementation of the antioxidants vitamin E (70 micro M) or N-acetyl-cysteine (NAC) (0.5 mM).. After 24 h in culture, the PBMLs of HD patients, but not those of CAPD patients, showed an apoptotic rate twice that of healthy controls and a 40% decrease of SHi levels (P < 0.01 in both). A negative correlation between the apoptotic rate and SHi was observed in both patients and controls (r = 0.648, P < 0.001). Plasma and ultrafiltrate samples from HD patients contained solutes (mainly in the low-middle molecular weight range) able to trigger apoptosis and oxidative stress in U937 cells. The treatment of HD patients with CL-E, as well as the in vitro supplementation of U937 cells with vitamin E or NAC during the exposure to uraemic plasma, decreased the rate of apoptosis and partially restored SHi.. This study showed an association between an increased apoptotic rate and decreased SHi in PBML of HD patients, but not of CAPD patients. These changes are partially due to different pro-apoptogens that accumulate in the plasma and are at least partially prevented by exogenous antioxidants able to restore SHi, such as vitamin E or thiol suppliers.

Topics: Aged; Apoptosis; Ascorbic Acid; Female; Humans; Kidney Failure, Chronic; Leukocytes, Mononuclear; Male; Middle Aged; Oxidative Stress; Peritoneal Dialysis; Renal Dialysis; Sulfhydryl Compounds; Ultrafiltration

Topics: Antioxidants; Ascorbic Acid; Humans; Kidney Failure, Chronic; Vascular Resistance

This study was undertaken to evaluate two different doses of folic acid and their effects on the control of hyperhomocysteinemia, and on pro-oxidant and antioxidant changes in a group of 32 hemodialysis (HD) patients. Blood samples were collected in a group of patients at three different times: before (basal; B), after the first (S1), and after the second (S2) three-month supplementation periods, and compared to samples from a group of healthy individuals. Analysis of vitamins (C, E, folate, and B12), oxidant parameters (lipid and protein oxidation), and homocysteine were performed. Hyperhomocysteinemia of different degrees was observed in all patients on HD (45.30 +/- 24.89 microM). Oxidative stress was also detected, with lipoperoxidation and protein oxidation being associated with lower concentrations of antioxidant substances (vitamins E and C). The first folate dose (2.5 mg after each dialysis session) reduced by half the initial concentrations of homocysteine (44.92 +/- 22.05 to 20.56 +/- 6.79 microM; p < 0.05) but did not normalize its values. The second dose (15 mg) did not show an additional effect, but it was at this time that lipoperoxidation was significantly reduced, although the protein oxidation showed no change. It was concluded that the first dose of folic acid was efficient in reducing homocysteine concentrations, without normalization of values. The participation of hyperhomocysteinemia in oxidative stress appeared to be partial, but in combination with dialysis treatment, may contribute to the induction of an oxidative environment in this group. The possible antioxidant action of folate must also be considered in this case, acting directly against lipoperoxidation or through hyperhomocysteinemia control. Routine supplementations of folic acid and other antioxidant vitamins should be considered in hemodialysis in order to reduce homocysteine levels to lower values, that although not normal, may be more beneficial in minimizing the cardiovascular risk in this group.

Topics: Ascorbic Acid; Dietary Supplements; Female; Folic Acid; Hematinics; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Lipid Peroxidation; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Proteins; Renal Dialysis; Vitamin B 12; Vitamin E

Hemodynamic maladjustment with predominant constriction at the efferent arteriole has been encountered in a variety of clinical settings of glomerulonephropathy. In essence, it induces not only intraglomerular hypertension but also exaggeratedly reduces the peritubular capillary flow, which supplies the tubulointerstitial compartment. The hemodynamic maladjustment is believed to reflect a glomerular endothelial cell dysfunction. In this regard, oxidative stress and antioxidant defect are likely responsible for the glomerular endothelial dysfunction. Improvement in renal function was accomplished following the correction of oxidant and antioxidant imbalance with antioxidant therapy and vasodilators. Following such therapy, there was a correction in hemodynamic maladjustment with a decline in intraglomerular hydrostatic pressure and an increase in renal perfusion with a subsequent increase in renal functions namely creatinine clearance, glomerular filtration rate and a decline in FEMg.

Topics: Ascorbic Acid; Glutathione; Glutathione Peroxidase; Hemodynamics; Humans; Kidney Failure, Chronic; Lipid Peroxidation; Nephrotic Syndrome; Oxidative Stress; Vitamin E

Oxidative stress plays a role in many disease states. These diseases have an increased incidence in uremia, and particularly in hemodialysis (HD) patients. This suggests an increased exposure to oxidative stress. An imbalance between oxidants and antioxidants has been suggested in uremic patients on HD. However, the respective influence of uremia and dialysis procedure has not been evaluated. It is postulated that antioxidant capacity in uremic patients is reduced, yet the mechanism remains unclear. We have determined the levels of lipid peroxidation expressed as thiobarbituric acid-reactive substances. We assessed oxidative protein damage by carbonyl content and activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in predialysis uremic patients and in end-stage renal disease (ESRD) patients before and after hemodialysis. Vitamin E and vitamin C levels, reduced glutathione and sulfhydryl content were also studied. We found enhanced oxidative stress in ESRD patients undergoing HD and in predialysis uremic patients. This was mostly due to defective antioxidant enzyme levels. Preventive modalities, including use of biocompatible membranes, ultrapure dialysate, exogenous supplementation of antioxidant vitamins, extracorporeal removal of reactive oxygen species (ROS) and oxidatively modified substances, would appear highly desirable to reduce complications in the long-term dialysis patients.

Topics: Antioxidants; Ascorbic Acid; Catalase; Erythrocytes; Glutathione Peroxidase; Humans; Kidney Failure, Chronic; Oxidative Stress; Renal Dialysis; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Uremia; Vitamin E

Food frequency questionnaires (FFQ) are frequently used in epidemiologic studies of nutrition and food intake. However, the use of FFQs in patients receiving maintenance dialysis has not been extensively studied. We hypothesize that FFQ is a useful tool to assess the food intake differences between patients receiving dialysis and patients not receiving dialysis.. Matched exposed-unexposed study with case-controlled design.. Outpatient dialysis unit affiliated with a tertiary-care community medical center.. From a pool of 102 maintenance hemodialysis (MHD) outpatients in a community dialysis unit, 30 adult MHD outpatients (15 men, 15 women, aged 55.8 +/- 14.6 years) were selected randomly as case subjects. They included 16 African Americans, 8 whites, 4 Hispanics, and 2 Asians. Eleven MHD patients took the multivitamin, Nephrovite (R&D Laboratories, Marina del Rey, CA), regularly. From an archive of 1,610 nondialytic individuals with known FFQ data, 30 control subjects were selected randomly to match the age, race, and sex of the case subjects.. We used Block's FFQ (version 98), an 8-page self-administered questionnaire that has been widely used in epidemiologic studies. A group of trained research assistants supervised the FFQ administration and interviewed those patients who were not able to answer all of the questions without assistance. Student t test was used to compare group means in form of daily dietary intake, and conditional logistic regression was used to calculate odds ratios for predetermined dichotomizing cutoff levels.. Food intake characteristics of MHD patients as compared with control patients not receiving dialysis.. Statistically significant differences between MHD case subjects and nondialytic control subjects were observed between the amounts of daily intake for vitamin C (84 +/- 63 mg/d v 127 +/- 70 mg/d, P = .01), dietary fiber (12 +/- 6 g/d v 18 +/- 11 g/d, P = .02), potassium (2,024 +/- 1,088 mg/d v 2,701 +/- 1,429 mg/d, P = .04), cryptoxanthin (56 +/- 88 microg/d v 140 +/- 118 microg/d, P = .003), and lycopene (2,052 +/- 2,234 microg/d v 4,524 +/- 3,979 microg/d, P = .004). These data indicate that MHD patients had a significantly lower intake of vitamin C, dietary fibers, potassium, and 2 of the carotenoid compounds when compared with individuals not receiving dialysis. Moreover, the daily intake of vitamin B(6) was significantly higher in MHD patients probably because of the high pyridoxine content in Nephrovite. By using the conditional logistic regression analysis, the odds ratios for lower than predetermined cutoff levels in patients receiving dialysis were significant for vitamin C, potassium, and the 2 previously mentioned carotenoids (odds ratio between 3.50 and 7.50, P < .05).. Patients receiving dialysis may consume significantly lower amounts of potassium, vitamin C, and dietary fibers as well as lower amounts of some carotenoids. The FFQ seems to be a useful tool to compare dietary intake of MHD patients with other groups, although it may underestimate the amount of daily protein and energy intake and, hence, may not be an accurate tool for individual assessment of food intake. More studies are required to evaluate the validity of the FFQ in dialysis patients. The lower vitamin C, fiber, and carotenoid intake of MHD patients may be atherogenic. Hence, the hypothesis is proposed that prescribed restrictions in potassium in MHD patients may lead to reduced fruit and vegetable intake, leaving meat and fats as the main source of calories. This may contribute to atherosclerosis and increased cardiovascular morbidity and mortality in these patients. This hypothesis needs to be evaluated in future studies.

Topics: Ascorbic Acid; Carotenoids; Case-Control Studies; Dietary Fiber; Dietary Supplements; Eating; Energy Intake; Female; Humans; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Odds Ratio; Potassium; Renal Dialysis; Reproducibility of Results; Sensitivity and Specificity; Surveys and Questionnaires

Several small clinical studies have reported that serum vitamin A levels were higher but serum vitamin C levels were lower among patients with end-stage renal disease. However, the relationship of antioxidant vitamins to renal function has not been studied in the general population. We examined the relationship of serum antioxidant vitamin levels to serum creatinine levels and risk for hypercreatininemia in a representative sample of 6,629 non-Hispanic whites, 4,411 non-Hispanic blacks, and 4,480 Mexican Americans aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey. Serum antioxidant vitamins were measured by isocratic high-performance liquid chromatography, and serum creatinine levels, by the modified kinetic Jaffé method. Serum vitamin A level was positively and significantly associated with serum creatinine level, whereas serum vitamin C level was inversely and significantly associated with serum creatinine level. A one-SD higher level of serum vitamin A (16.9 microg/dL) was associated with a 2.53-fold (95% confidence interval, 1.96 to 3.27; P < 0.001), 2.07-fold (95% confidence interval, 1.84 to 2.33; P < 0.001), and 2.76-fold (95% confidence interval, 1.74 to 4.37; P < 0.001) greater risk for hypercreatininemia among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans, respectively. A one-SD higher serum vitamin C level (0.45 mg/dL) was associated with a 22% (95% confidence interval, 0.06 to 0.35; P = 0.01) and 42% (95% confidence interval, 0.08 to 0.62; P = 0.02) lower risk for hypercreatininemia in non-Hispanic whites and Mexican Americans. Our study provides useful information to support the hypothesis that antioxidant vitamins may have an important role in the pathogenesis of chronic renal failure.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Creatinine; Cross-Sectional Studies; Ethnicity; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Odds Ratio; Population Surveillance; Regression Analysis; Risk Factors; United States; Vitamin A; Vitamin E; Vitamins

One tablet of Sorbifer Durules contains 100 mg Fe2+ and 60 mg vitamin C. The authors examined in a short-term study 24 haemodialyzed patients with chronic renal failure of different etiology. The investigation was divided into three parts. During the first 4 weeks the patients did not receive Fe2+ nor vitamin C. During the subsequent four weeks the patients had Sorbifer Durules, one tablet/24 hours. This period was followed by another four weeks when the patients went again without Fe2+ and vitamin C treatment. At regular intervals, i.e. on days 0, 28, 56 and 84 the authors assessed the packed cell volume, blood haemoglobin and serum iron level, the total iron binding capacity, transferrin saturation, ferritin, and vitamin C in serum as well as the plasma oxalic acid level. Four weeks treatment using Sorbifer Durules led to a significant rise of the packed cell volume and haemoglobin in blood, iron and vitamin C in serum. This treatment did not affect the oxalic acid plasma level. Oral treatment with Sorbifer Durules, one tablet/24 hours, was adequate for maintaining the serum iron concentration in haemodialyzed patients during treatment with recombinant human erythropoietin. This treatment prevented at the same time the development of vitamin C deficiency in serum and a further rise of plasma oxalic acid in these patients.

Topics: Administration, Oral; Anemia; Ascorbic Acid; Drug Combinations; Female; Ferrous Compounds; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Tablets

Oxalic acid is one of the well-known uremic toxins that participates in the pathogenesis of uremic syndrome. Secondary hyperoxalemia is a common feature in patients with chronic renal failure, but oxalate removal is not adequately accomplished by renal replacement therapy. In our series of patients, the plasma level of oxalic acid was significantly elevated, while the plasma vitamin C was in the normal range or in the upper margin of the normal range. The peritoneal clearance of oxalic acid was significantly lower in comparison to the peritoneal clearance of urea. Peritoneal clearance and peritoneal transfer of oxalic acid and other examined parameters increased using dialysis solution containing 2.5% glucose in comparison to dialysis solution containing 1.5% glucose. The significant hyperoxalemia of our patients persisted despite the relatively high peritoneal transfer of oxalic acid during continuous ambulatory peritoneal dialysis. The clearance of oxalic acid related to the clearance of urea was 58.1% during hemodialysis, 74.2% during postdilution hemofiltration, and 69.0% during postdilution hemodiafiltration. The sieving coefficient of oxalic acid during postdilution hemofiltration was 74.0% of urea sieving coefficient. The most significant decrease of plasma oxalic acid was observed during postdilution hemodiafiltation (63.3%). These results suggest that currently, renal replacement therapy is not effective enough for a permanent reduction of plasma oxalic acid.

Topics: Adult; Ascorbic Acid; Female; Hemodiafiltration; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Renal Replacement Therapy; Toxins, Biological; Uremia

The high incidence of cardiovascular diseases in chronic renal failure (CRF) and hemodialyzed (HD) patients is now well established and the involvement of oxidative stress has been hypothesized in these phenomena. The aim of our study was to evaluate the level of oxidative stress in healthy controls (CTL) compared with CRF and HD patients before (pre-HD) and after (post-HD) the dialysis session, carried out on a high biocompatible polyacrylonitrile membrane AN69.. Several indicators of the extracellular redox status were evaluated in plasma. The ascorbyl free radical (AFR) was directly measured using electron spin resonance spectroscopy (ESR) and expressed with respect to the vitamin C level to obtain a direct index of oxidative stress. Indirect plasma parameters such as vitamin E, thiol and uric acid levels were also quantified. The plasma antioxidant status (PAS) was evaluated by the allophycocyanin test. Nitric oxide (NO) stable-end metabolites: nitrites and nitrates (NO(x)), were measured in plasma.. In CRF patients, vitamin C and thiol levels were low, and the AFR/vitamin C ratio high compared with the CTL. On the other hand, PAS and uric acid levels were shown to be higher in CRF patients. After the dialysis session, vitamin C level decreased and AFR/vitamin C ratio increased. The thiol levels were shown to be increased, in return PAS and uric acid levels were significantly lower after the dialysis session. NO(x) levels rose during CRF, but were significantly decreased after the dialysis procedure. No differences in vitamin E status were observed between CTL, CRF and HD patients.. Our study demonstrates that profound disturbances in the extracellular redox system occur during the course of chronic renal failure and hemodialysis, and may provide an explanation for the cardiovascular complications in these patients.

Topics: Aged; Analysis of Variance; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Case-Control Studies; Cholesterol; Electron Spin Resonance Spectroscopy; Female; Free Radicals; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Oxidative Stress; Renal Dialysis; Risk Factors; Sulfhydryl Compounds; Uric Acid; Vitamin E

I.v. ascorbic acid has been used in an effort to mobilize ferritin stores in hyporesponsive HD patients receiving Epoetin alfa. However, not all patients who respond to i.v. ascorbic acid therapy will have subsequent decline in feritin stores (Gastaldello et al., 1995; Tarng & Huang, 1998). Additionally, predicting those patients who will overcome their Epoetin alfa hyporesponsiveness remains unclear. Ascorbic acid's effect on hemosiderin deposits may be another possible mechanism to the increased Epoetin alfa response observed in some HD patients (Hemosiderin is a pathologic deposition of iron in tissues including the spleen, small intestine, and bone marrow). Although there are no well-controlled studies evaluating hemosiderin and i.v. ascorbic acid, it should be noted that subjects with scurvy often present with excessive iron deposits in the tissues, indicating the possible effects of ascorbic acid on hemosiderin metabolism (Bothwell et al., 1964). Ascorbic acid deficiency is often present in many HD patients due to its removal during dialysis and lack of dietary intake (Ponka & Kuhlback, 1983). It remains controversial whether oral ascorbic acid supplementation is indicated in patients receiving HD. Therefore, the Recommended Daily Allowance (RDA) of 60 mg/day should be advised (Makoff, 1999). I.v. ascorbic acid should be considered as a possible adjuvant to therapy in patients who are "iron-overloaded" and hyporesponsive to Epoetin alfa. Although the long-term effects of i.v. ascorbic acid on HD patients is unknown, the potential risk of secondary oxalosis should be considered (Costello, 1991; Pru, Eaton, & Kjellstrand, 1985). It may be necessary to monitor plasma oxalate levels if long-term therapy with i.v. ascorbic acid is used. Clinical studies have examined i.v. ascorbic acid doses from 300 mg-500 mg given up to TIW for a maximum duration of 12 weeks without any significant deleterious effects (Gastaldello et al., 1995; Tarng & Huang, 1998; Tarng et al., 1999). However, large-scale, prospective, and controlled trails are needed to determine the long-term safety and efficacy of i.v. ascorbic acid therapy in iron overloaded HD patients receiving Epoetin alfa.

Topics: Anemia; Antioxidants; Ascorbic Acid; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins

Aging and age-related diseases are associated with the production of reactive oxygen species which modify lipids, proteins and DNA. Here we hypothesized the glyco- and lipoxidation product N(epsilon)-(carboxymethyl)lysine (CML) in proteins should bind divalent and redox active transition metal binding. CML-rich poly-L-lysine and bovine serum albumin (BSA) were chemically prepared and found to bind non-dialyzable Cu(2+), Zn(2+) and Ca(2+). CML-BSA-copper complexes oxidized ascorbate and depolymerized protein in the presence of H(2)O(2). CML-rich tail tendons implanted for 25 days into the peritoneal cavity of diabetic rats had a 150% increase in copper content and oxidized ascorbate three times faster than controls. CML-rich proteins immunoprecipitated from serum of uremic patients oxidized four times more ascorbate than control and generated spin adducts of DMPO in the presence of H(2)O(2). The chelator DTPA suppressed ascorbate oxidation thereby implicating transition metals in the process. In aging and disease, CML accumulation may result in a deleterious vicious cycle since CML formation itself is catalyzed by lipoxidation and glycoxidation.

Topics: Animals; Ascorbic Acid; Binding Sites; Biopolymers; Catalysis; Cations, Divalent; Collagen; Copper; Diabetes Mellitus, Experimental; Free Radicals; Glycation End Products, Advanced; Humans; Hydrogen Peroxide; Kidney Failure, Chronic; Lysine; Methylation; Oxidation-Reduction; Oxidative Stress; Peroxidase; Rats; Rats, Sprague-Dawley; Serine

We investigated whether the total peroxyl radical-trapping antioxidant potential (TRAP) assay, which has recently been proposed as a gauge of oxidative stress, could serve to evaluate plasma and low density lipoprotein (LDL) antioxidant state in hemodialysis (HD) patients.. TRAP was determined by the lag time of the chemiluminescence reaction induced by azo-initiator-catalyzed linoleic acid peroxidation in the plasma and corresponding LDL preparations of 23 HD patients and 22 healthy subjects. Antioxidant systems, including glutathione peroxidase (GSH-Px), ascorbate, vitamin E, and uric acid, oxidative stress markers including malondialdehyde (MDA), carbonyls, and advanced oxidation protein products (AOPP), and lipids, including cholesterol and triglycerides, were also determined in the plasma.. Both plasma and LDL-TRAP were significantly increased in HD patients despite decreased GSH-Px and ascorbate and increased MDA, carbonyl, and AOPP plasma levels. Plasma TRAP values were closely related to both uric acid and AOPP levels, and LDL-TRAP values were related to triglycerides and AOPP levels. In vitro studies showed that: (a) plasma TRAP of control plasma increased regularly with supplementation of uric acid, although not reaching that of HD plasma with similar uric acid levels; (b) the addition of human serum albumin-AOPP also regularly increased control plasma TRAP, but was close to that of HD plasma with similar AOPP levels; and (c) LDL-TRAP was increased following LDL enrichment with triglycerides.. Our study demonstrates that TRAP is not a relevant parameter for evaluating plasma or LDL antioxidant capacity in HD patients, due to the high plasma levels of uric acid, triglycerides and AOPP, which by themselves do not exert efficient antioxidant activity in vivo, but in vitro are able to scavenge the peroxyl radicals involved in the TRAP assay.

Topics: Aged; Antioxidants; Ascorbic Acid; Biomarkers; Female; Free Radical Scavengers; Glutathione Peroxidase; Humans; Kidney Failure, Chronic; Lipoproteins, LDL; Male; Malondialdehyde; Middle Aged; Oxidation-Reduction; Oxidative Stress; Renal Dialysis; Triglycerides; Uric Acid; Vitamin E

The authors describe the effect of a single i.v. dose of 20 mg furosemide on the excretion of oxalic acid, vitamin C and vitamin B6 in a control group and in patients with chronic renal failure without dialyzation treatment. An increased urinary excretion of oxalic acid, vitamin C and vitamin B6 was found during the first three hours after furosemide administration in both groups. The effect of furosemide persisted for six hours in patients with chronic renal failure without dialyzation treatment. The authors described a new hitherto unknown positive side-effect of furosemide, i.e. enhanced urinary oxalic acid excretion in the control group and in patients with chronic renal failure without dialyzation treatment and a negative side-effect of furosemide, i.e. increased urinary vitamin B6 excretion in both examined groups. With regard to the assembled results the authors recommend in addition to monitoring of vitamin C also monitoring of vitamin B6 in plasma during long-term administration of large doses of furosemide to patients with chronic renal failure as deficiency of these vitamins could develop.

Topics: Adult; Ascorbic Acid; Diuretics; Female; Furosemide; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalic Acid; Pyridoxine

Recent studies have demonstrated a marked increase in the level of advanced glycation end products (AGEs) in the plasma, skin and amyloid fibrils of hemodialysis (HD) patients. The presence of AGEs in (beta2m) forming amyloid fibrils has been established in a previous immunochemical study relying on a monoclonal anti-AGE antibody. In the present study, Western blot analysis and immunohistochemistry reveal that the epitope recognized by this antibody is N epsilon-(carboxymethyl)lysine (CML) and that CML is one of the AGE structures present in amyloid fibrils. Thus, two AGE structures, CML and pentosidine, are now recognized in dialysis-related amyloidosis. AGE accumulation in uremia is not accounted for by elevated glucose levels. Since CML and pentosidine formation are closely linked to oxidative processes, we tested the hypothesis that a high oxidative stress enhanced AGE formation in HD patients. We focused on ascorbic acid (AA) because AA is easily oxidized under oxidative stress and its oxidized form (oxiAA) is a source of CML and pentosidine. In vitro incubation of beta2m with AA under atmospheric oxygen resulted in: (1) the rapid appearance of characteristic physicochemical properties of AGEs (brown color, fluorescence, polymerization tendency); (2) the transformation of beta2m into AGE-modified beta2m recognized by a specific monoclonal antibody; and (3) the accelerated formation of CML in beta2m and beta2m-peptide, recognized by mass spectrometry. A similar in vitro incubation of human serum albumin disclosed a parallel production of pentosidine measured by high-performance liquid chromatographic assay. In HD patients, the degree of AA oxidation, assessed as the ratio of oxiAA to total ascorbate, was more than twice as high as that of normal subjects (0.87 +/- 0.16 vs. 0.35 +/- 0.11, P < 0.0001), suggesting the presence of an increased oxidative stress. Interestingly, plasma level of oxiAA was correlated with the plasma levels of protein linked (P < 0.01, r2 = 0.25) and free (P < 0.05, r2 = 0.22) pentosidine. Altogether these results demonstrate that AGE, that is, CML and pentosidine, production is accelerated under oxidative stress, even in the absence of glucose. They suggest that, in uremia, CML and pentosidine production is determined both by an increased oxidative stress and the availability of precursors such as oxiAA. Finally, both CML and pentosidine contribute to the AGEs present in dialysis-related amyloid fibrils.

Topics: Amino Acid Sequence; Amyloid; Arginine; Ascorbic Acid; beta 2-Microglobulin; Glycation End Products, Advanced; Humans; Immunohistochemistry; In Vitro Techniques; Kidney Failure, Chronic; Lysine; Molecular Structure; Oxidative Stress; Renal Dialysis; Spectrometry, Fluorescence; Spectrometry, Mass, Fast Atom Bombardment; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Uremia

The vitamin C status of patients with chronic renal failure (CRF), dialysis patients (DP) and patients after renal transplantation (RT) was the object of this investigation. Levels of vitamin C intake from dietary records were estimated at mean values of 93.5 mg/d (CRF), 65.5 mg/d (DP) and 163.9 mg/d (RT). Compared to the recommendation of the German Society of Nutrition (75 mg/d), this indicated a normal range of supply for all groups except the group of DP. The corresponding mean plasma concentrations were 62.2 mumol/l (CRF), 80.3 mumol/l (DP) and 68.8 mumol/l (RT). Supplements of 60 or 100 mg vitamin C given to patients of the DP-group after each dialysis session showed slightly, but not significantly higher concentrations of vitamin C in plasma. During dialysis treatment, plasma vitamin C concentrations dropped to approximately 50% of the basal value, but almost reached initial levels again 44 hours later, both with and without supplementation. During one treatment period, vitamin C loss in the dialysate of three patients ranged between 92.5 and 333.6 mg. The amount of vitamin C in plasma, however, dropped to approximately 50% of the basal value for these patients, too.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Nutritional Requirements; Nutritional Status; Renal Dialysis

Oxidative modification of plasma lipoproteins increases their atherogenicity. Nutritive antioxidants, including carotenoids, can prevent such lipoperoxidation and may protect against atherosclerosis. Plasma retinol, ascorbate, alpha-tocopherol and four carotenoids (lutein, lycopene, alpha-carotene and beta-carotene) were measured using HPLC in 45 patients with chronic renal failure (CRF) and in 21 controls. Plasma retinol was significantly increased in patients with CRF (conservative therapy mean of 3.7 mumol/l vs. 1.9 mumol/l; p < 0.001). Plasma lycopene was significantly lower in patients with CRF (healthy mean 0.44 mumol/l vs. conservative therapy mean 0.27 mumol/l and haemodialysis mean of 0.17 mumol/l; p < 0.001), a finding that persisted even after adjusting for plasma cholesterol. Low circulating antioxidant lycopene levels may contribute to an already impaired antioxidant defence system in patients with CRF. The process of haemodialysis further compromises antioxidant defences, principally by removing water-soluble ascorbate and urate, but does not appear to affect circulating carotenoid concentrations.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Carotenoids; Cholesterol; Humans; Kidney Failure, Chronic; Lycopene; Middle Aged; Renal Dialysis; Uric Acid; Vitamin A; Vitamins

Urinary oxalic acid excretion was examined in 61 patients with chronic nephropathies and in 21 patients after renal transplantation with a varying mean glomerular filtration. In both groups of patients a correlation was found between the plasma oxalic acid and serum creatinine and by a hyperbolic correlation between plasma oxalic acid and creatinine clearance. Moreover the authors found a direct correlation between oxalic acid and FEoxalic acid and FE(Na)+, FEH20 and FE1-ascorbic acid in both patient groups. Various chronic nephropathies and treatment in both groups did not affect the revealed correlations. In 13 healthy subjects during the period of maximum water diuresis urinary Na+ excretion did not increase but there was a significant increase of the l-ascorbic acid and oxalic acid excretion. In a group of 8 patients in the polyuric stage of chronic renal failure without dialysis treatment under conditions of increased dietary NaCl intake (15 g/24 h) a significant increase of the urinary Na+ excretion was recorded while the l-ascorbic acid and oxalic acid excretion was unaltered. From the assembled values of the examined biochemical indicators ensues that urinary oxalic acid excretion, similarly as ascorbic acid excretion, depended on water excretion.

Topics: Adult; Ascorbic Acid; Creatinine; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Oxalates; Oxalic Acid; Sodium

Cardiovascular disease is the major cause of mortality in patients receiving hemodialysis for chronic renal failure. Increased lipid peroxidation and depletion of chain-breaking antioxidants may contribute to increased risk of atherosclerosis. We have therefore assessed the effect of a single episode of hemodialysis on antioxidant status in 22 patients and control subjects. Overall, total antioxidant capacity of serum was increased in dialysis patients, but there was a marked reduction after hemodialysis [571 +/- 31 vs 342 +/- 22 mumol/L Trolox (water-soluble vitamin E analog) equivalents, P < 0.001]. The increase in total antioxidant capacity before hemodialysis was almost entirely due to relatively high serum urate. Among individual chain-breaking antioxidants, dialysis led to a decrease in urate (398 +/- 15 vs 136 +/- 12 mumol/L, P < 0.001), ascorbate (10.5 +/- 1.7 vs 5.9 +/- 1.0 mumol/L, P < 0.01), and lipid-corrected tocopherol (4.70 +/- 0.56 vs 4.26 +/- 0.39 mumol/mmol cholesterol, P < 0.05). Protein thiol groups increased after dialysis (328 +/- 16 vs 422 +/- 22 mumol/L, P < 0.001), whereas albumin remained unchanged (40.1 +/- 1.1 vs 41.0 +/- 1.6 g/L, not significant). Although total antioxidant capacity of serum is increased in hemodialysis patients, depletion of key chain-breaking antioxidants may lead to accelerated atherogenesis.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Blood Proteins; Cholesterol; Female; Humans; Kidney Failure, Chronic; Male; Malondialdehyde; Middle Aged; Renal Dialysis; Serum Albumin; Sulfhydryl Compounds; Uric Acid; Vitamin E

Patients with chronic renal failure, including those receiving regular long-term haemodialysis, have a high incidence of premature cardiovascular disease. Oxidative stress, which occurs when there is excessive free-radical production or low antioxidant levels, has recently been implicated as a causative factor in atherogenesis. The aim of this study was to determine if chronic renal failure and haemodialysis were associated with increased oxidative stress. Serum malondialdehyde was measured as a marker of lipid peroxidation in 15 patients with conservatively managed chronic renal failure (CRF), 15 patients with CRF undergoing regular haemodialysis and 15 healthy controls. Selenium, glutathione peroxidase and antioxidant vitamins were also measured. Malondialdehyde was elevated in dialysis patients in comparison to CRF and control groups (dialysis 1.16 +/- 0.08 mumol/l, CRF 0.94 +/- 0.07, controls 0.66 +/- 0.10). Antioxidants, including vitamin C, selenium and glutathione peroxidase, were decreased in dialysis patients and to a lesser extent in the CRF group (vitamin C-dialysis 16.43 +/- 3.76 mumol/l, CRF 34.5 +/- 8.6, controls 56.11 +/- 7.41; selenium-dialysis 0.77 +/- 0.07 mumol/l, CRF 0.69 +/- 0.06, controls 1.09 +/- 0.06: glutathione peroxidase-dialysis 101 +/- 5 U/l, CRF 160 +/- 11, controls 290 +/- 10). These findings indicate oxidative stress in patients with CRF which is further exacerbated by haemodialysis, as evidenced by increased lipid peroxidation and low antioxidant levels. This stress may play a role in the development of atherosclerosis in these groups.

Topics: Adult; Aged; Ascorbic Acid; Female; Glutathione Peroxidase; Humans; Kidney Failure, Chronic; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Renal Dialysis; Selenium

We use oxalate oxidase from barley seedlings for the colorimetric determination of oxalate in plasma. The oxalate is converted to hydrogen peroxide, which, in the presence of peroxidase, is detected by a Trinder-like chromogenic system. Optimization of the assay, including deproteinization and elimination of interferences from reducing substrates, is described. Ascorbate additions (200 mumol/L) did not affect oxalate concentration in plasma, even after long frozen storage. Mean analytical recovery of oxalate averaged 102% +/- 6.9%, imprecision (CV) at 2.0 mumol/L was 7.2%, and the lower limit of quantification (CV = 20%) was 0.6 mumol/L. Results correlated well with those by chromatography (r = 0.999, Sy/x = 0.29 mumol/L, n = 32, range for x, y = 0-140 mumol/L). Plasma oxalate concentrations measured in 32 healthy subjects ranged from 0.6 to 2.9 mumol/L (mean 1.28, SD 0.71 mumol/L), which agrees with those measurable by using indirect radioisotopic dilution methods. Patients with primary hyperoxaluria and chronic renal failure exhibited markedly greater plasma concentrations of oxalate.

Topics: Adolescent; Adsorption; Adult; Ascorbic Acid; Benzenesulfonates; Blood Proteins; Charcoal; Child; Chromogenic Compounds; Colorimetry; Drug Stability; Female; Freezing; Hordeum; Humans; Hyperoxaluria; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid; Oxidoreductases; Quality Control; Reference Values; Salicylates; Sensitivity and Specificity

A 71-year-old woman was admitted with end-stage renal failure and histological evidence of oxalosis. This case of diffuse renal tubular crystal calcium oxalate deposits seems to be induced by long-term piridoxilate therapy (10 years) or simultaneous intake of both piridoxilate and vitamin C (500 mg/day for 6 months), since no other cause of secondary oxalosis could be found. So, it seems necessary to monitor the serum creatinine level, especially in the elderly, during piridoxilate therapy and to avoid high vitamin C intakes in patients under such treatment to prevent development of renal insufficiency.

Topics: Aged; Angina Pectoris; Ascorbic Acid; Calcium Oxalate; Creatinine; Drug Interactions; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Tubules; Pyridoxine; Time Factors; Vasodilator Agents

Plasma levels of ascorbic acid (AA) and dehydroascorbic acid (DHA) were estimated in 27 patients of end stage renal failure (ESRF) on standard conservative therapy (group A) and 9 patients of ESRF on maintenance haemodialysis (MHD; group B). Fourteen healthy subjects matched for age and sex served as control (group C). The dietary intake of vitamin C was significantly decreased in group A than in group B compared to control. Similarly, plasma AA was significantly lowered to 0.801 +/- 0.283 mg per cent in group A compared to 1.421 +/- 0.47 mg per cent in control. While it was just lowered to 1.058 +/- 0.272 mg per cent in group B. Although plasma level of DHA was raised to 0.243 +/- 0.486 mg per cent and 0.166 +/- 0.54 mg per cent in groups A and B respectively, the increase was not statistically significant. In our present study, the DHA/AA ratio was found to be inversely proportional to the plasma AA. Further, this ratio has been claimed to be a better indicator of overall reducing atmosphere (i.e., profile of vitamin C) of the body.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Dehydroascorbic Acid; Eating; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Uremia

We studied the effect of vitamin C and B6 supplementation on oxalate metabolism in seven patients receiving chronic peritoneal dialysis therapy. The study was divided into three phases, each lasting 4 weeks. Plasma oxalate, total ascorbic acid, and pyridoxal-5'-phosphate (PLP) were measured at the end of each phase. Twenty-four-hour urinary excretion and dialysate removal rates of oxalate were also obtained. At the end of phase I (supplement-free period), plasma oxalate levels were markedly elevated at 47.6 +/- 7.1 mumol/L (437 +/- 66 micrograms/dL) (normal, 3.4 +/- 0.4 mumol/L [30.3 +/- 1.6 micrograms/dL]). Plasma total ascorbic acid levels were 62 +/- 6 mumol/L (1.0 +/- 0.1 mg/dL) (normal, 45 to 57 mumol/L [0.8 to 1.0 mg/dL]), while plasma PLP levels were markedly reduced to 24 +/- 5 nmol/L (normal, 40 to 80 nmol/L). Daily supplements of 0.57 mmol (100 mg) ascorbic acid orally (phase II) resulted in a 19% increase in the plasma oxalate levels to 57.8 +/- 6.1 mumol/L (520 +/- 55 micrograms/dL) (P less than 0.03), with a concomitant 60% increase in the plasma ascorbate levels (91 +/- 6 mumol/L [1.6 +/- 0.1 mg/dL], P less than 0.01). Plasma PLP values remained low. Finally, during phase III (0.57 mmol or 100 mg ascorbic acid plus 59.6 mumol or 10 mg pyridoxine HCI orally daily), plasma oxalate levels declined by 17% to 47.9 +/- 5.2 mumol/L (431 +/- 47 micrograms/dL) (P greater than 0.05 v phase II).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Ascorbic Acid; Humans; Hyperoxaluria; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Peritoneal Dialysis, Continuous Ambulatory; Pyridoxal Phosphate; Pyridoxine

The cause of secondary hyperoxalemia and oxalosis in patients on maintenance dialysis is unknown. The oxalate removal rate was determined in 26 patients on maintenance hemodialysis and 6 on continuous ambulatory peritoneal dialysis by measuring oxalate removed by dialysis and urinary excretion. The role of vitamin B6 deficiency and ascorbate in the raised plasma oxalate concentrations of these patients was evaluated. Plasma oxalate in hemodialysis patients, 442 +/- 41 micrograms/100 mL (mean +/- SE), and peritoneal patients, 394 +/- 115 micrograms/100 mL, were significantly higher than that in normal subjects, 11 +/- 1 microgram/100 mL (P less than 0.001). Average daily oxalate removal in subjects on hemodialysis, based on dialysis losses and urinary excretion, 35 +/- 3 mg/24 h, was significantly greater than urinary excretion of normal subjects, 26 +/- 1 (P less than 0.01). Oxalate removal from peritoneal dialysis patients, 28 +/- 2 mg/24 h, was not significantly different from that of hemodialysis patients or urinary excretion of normal subjects. Plasma ascorbate and B6 status were not correlated with plasma oxalate. A positive correlation between B6 deficiency and oxalate removal rate was not found. Plasma oxalate was correlated with time on dialysis (all patients) (P = 0.02). In a separate study of 15 hemodialysis patients followed over 2.3 +/- 0.2 yr, both plasma oxalate and oxalate removal rate significantly increased, P less than 0.001 and 0.05, respectively. It was concluded that oxalate removal rate is increased in hemodialysis patients and that the increased total body oxalate burden in these patients is not due to decreased removal. Although the increase may result from increased oxalate synthesis or gastrointestinal absorption, B6 deficiency and increased plasma ascorbate do not play a role.

Topics: Alanine Transaminase; Ascorbic Acid; Erythrocytes; Humans; Intestinal Absorption; Kidney Failure, Chronic; Oxalates; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Vitamin B 6 Deficiency

Ascorbic acid supplements are commonly prescribed to patients with end-stage renal disease receiving peritoneal dialysis. To establish the need for ascorbic acid supplements, we evaluated seven chronic peritoneal dialysis patients during a supplement-free (phase I) period, and while receiving oral ascorbic acid (0.57 mmol/d [100 mg/d]) (phase II). Because of a proposed interaction with vitamin B6, patients were additionally supplemented with pyridoxine HCl (59.6 mumol/d [10 mg/d]) (phase III). Plasma levels and dialysate removal rates of total ascorbic acid and plasma pyridoxal-5-phosphate (PLP) were measured at the end of each phase. During phase I, plasma ascorbic acid levels (normal, 45 to 57 mumol/L [0.8 to 1.0 mg/dL]) declined slightly from 74 +/- 11 mumol/L (1.3 +/- 0.2 mg/dL) to 62 +/- 11 mumol/L (1.1 +/- 0.2 mg/dL) (P less than 0.02) at the end of the third week, and then remained stable to the end of the fourth week. Plasma ascorbic acid levels were no different in patients with or without residual renal function. With the addition of vitamin C supplements, plasma ascorbic acid levels increased by 45% of the baseline value at the end of phases II (P less than 0.001). The dialysate removal rate of ascorbic acid was 0.28 +/- 0.03 mmol/d (50 +/- 6 mg/d) at the end of phase I, and increased by 57% of the baseline value at the end of phases II (P less than 0.001). However, the peritoneal clearance of ascorbic acid remained unchanged during all phases the study. Pyridoxine depletion or repletion had no effect on plasma ascorbic acid levels (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Ascorbic Acid; Diet; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nutritional Requirements; Peritoneal Dialysis, Continuous Ambulatory; Pyridoxal Phosphate; Pyridoxine

An ion chromatographic procedure for the determination of plasma oxalate is proposed, in which the ultrafiltered sample is injected into an ion-chromatographic system. Sample processing appears effective in avoiding spontaneous oxalogenesis. Sensitivity (down to 1.0 mumol/l) allows determinations in normal and pathological samples; recoveries from plasma ultrafiltration are 94.6 +/- 11.7%. Protein binding was investigated and precautions to improve recoveries from plasma ultrafiltration are proposed. The technique is simple to perform from healthy controls averaged 6.75 +/- 2.62 mumols/l (mean +/- S.D. n = 18); samples from patients with primary hyperoxaluria and chronic renal failure undergoing regular dialysis were also analysed and some of the data obtained are reported and discussed.

Topics: Adult; Ascorbic Acid; Chromatography, Ion Exchange; Glyoxylates; Humans; Hyperoxaluria; Indicators and Reagents; Kidney Failure, Chronic; Oxalates; Reference Values; Ultrafiltration

We measured levels of N-nitrosodimethylamine (NDMA) in peripheral blood from 13 fasting male patients, 30-74 years old, who had chronic renal failure, and in five healthy control subjects (four males and one female) 31-50 years old. In the patients, we found significant (P less than .01) levels of NDMA (mean +/- SD; 201 +/- 111 ng/kg of blood), which is known to be carcinogenic in animals. Five minutes after oral administration of ethanol (0.4 g/kg of body weight), all patients exhibited a significant (P less than .01) rise in blood NDMA levels (338 +/- 125 ng/kg), suggesting continuous endogenous formation of NDMA that was unmasked by ethanol's ability to inhibit first-pass hepatic metabolism of NDMA. In five of six patients, pretreatment with oral ascorbic acid resulted in a blunting, but not statistically significant, effect on maximum blood NDMA levels after consumption of ethanol. Mean levels were 340 +/- 100 ng/kg before treatment with ascorbic acid and 237 +/- 127 ng/kg during treatment. Ethanol administration unmasks increased gastrointestinal formation of NDMA in patients with chronic renal failure. Further studies are required to confirm a possible link between endogenous NDMA formation and the increased incidence of cancer in these patients.

Topics: Adult; Aged; Analysis of Variance; Ascorbic Acid; Digestive System; Dimethylnitrosamine; Ethanol; Female; Humans; Kidney Failure, Chronic; Liver; Male; Middle Aged

Urinary calculi found in 4 patients on chronic hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) were identified as protein calculi by infrared spectroscopic analysis. Positive Congo red staining and immunological assessment revealed that the calculi were composed of amyloid protein derived from beta 2-microglobulin. A comparison of the patients who excreted calculi with 10 patients on chronic dialysis without urinary calculi showed no significant differences in the urinary and serum levels of beta 2-microglobulin. The mechanism of amyloid calculus formation may involve factors independent of the concentration of beta 2-microglobulin in urine or serum. Urinary calculi found in patients on chronic hemodialysis or CAPD were composed of amyloid protein derived from beta 2-microglobulin.

Topics: Amyloid; Ascorbic Acid; beta 2-Microglobulin; Humans; Immunodiffusion; Kidney Failure, Chronic; Renal Dialysis; Spectrophotometry, Infrared; Uric Acid; Urinary Calculi

In order to assess the necessity of vitamin supplementation for patients who are receiving haemodialysis, measurements of vitamin status were made, and both dietary and supplementary intakes were assessed, in 26 patients who were undergoing haemodialysis. Blood samples were collected from these patients before they underwent haemodialysis, after an overnight fast, for the measurement of plasma retinol, alpha-tocopherol and ascorbate levels. Serum and erythrocyte folate levels were measured also. Thiamin status was assessed by the effect of added thiamin pyrophosphate on erythrocyte transketolase activity and pyridoxine status was assessed by the effect of added pyridoxal-5'-phosphate on erythrocyte aminotransferase activity. All patients had elevated plasma retinol levels; 48% of patients had elevated plasma alpha-tocopherol levels; the plasma ascorbate level was low in 50% of patients but was elevated in 25% of patients; and plasma and erythrocyte folate levels were elevated in 76% and 91% of patients, respectively. Thiamin status was normal in all but one patient and the pyridoxine level appeared to be low in two other patients. Many patients had low dietary intakes of vitamin C, folate and vitamin B6. We conclude that supplements of vitamins A and E are not required and, when dietary intakes of water-soluble vitamins are marginal, these should be supplemented at a dose as near as possible to the recommended dietary intake.

Topics: Ascorbic Acid; Female; Humans; Kidney Failure, Chronic; Male; Pyridoxine; Renal Dialysis; Riboflavin; Thiamine; Vitamin A; Vitamin E; Vitamins

Changes of the antioxidative homoeostasis in hemodialysis patients were registered by determination of the antioxidative capacity (AC). This capacity has been increased before dialysis and decreased by 50% during dialysis. After 30 minutes of dialysis the AC was much more decreased than creatinine and urea. The cause of this AC reduction is not only a loss of antioxidants into the dialysate, but possibly also an oxygen radical formation by C5a-activated granulocytes, sequestered in pulmonary capillaries during transient leucopenia.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Creatinine; Female; Free Radicals; Homeostasis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxidation-Reduction; Oxygen; Renal Dialysis; Urea; Vitamin E

We have previously reported that hyperoxalemia can be aggravated by vitamin C supplementation in regular hemodialysis patients. The present study was undertaken to examine the validity of this observation in an experimental setting. Fifty five-sixths nephrectomized rats were divided into two groups: 30 rats were allowed free access to water containing 8 mg/ml of vitamin C (100-160 mg/100 g/24 h) and the remainder given tap water without vitamin C. The serum creatinine increased and the Hct decreased gradually; however, there was no difference between the two groups. Plasma vitamin C, oxalate and urinary oxalate levels were higher in the vitamin -treated group than the nontreated rats. Histological examination revealed glomerular and interstitial fibrosis and round cell infiltration as well as tubular cyst formation. Oxalate deposits in renal tubules were found only in vitamin C-treated rats with advanced renal failure. Nontreated animals with equally advanced renal impairment showed no oxalate deposits. These results confirm our previous clinical findings that vitamin C supplementation aggravates the secondary oxalosis of chronic renal failure.

Topics: Animals; Ascorbic Acid; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Tubules; Male; Nephrectomy; Oxalates; Oxalic Acid; Rats; Rats, Inbred Strains

We studied L-ascorbic acid absorption in rats subjected to subtotal nephrectomy (renal failure (RF) group) and compared the results with those obtained in sham-operated normal animals and those pair-fed with their azotemic counterparts (PF group). In vivo recirculating perfusion and in vitro everted sac techniques were employed. The in vitro experiments were repeated substituting buffer within the serosal compartment with pooled sera from uremic and normal individuals. L-Ascorbic acid absorption in vivo in the RF group was significantly lower than those found in normal control and PF groups. In contrast, the in vitro mucosal to serosal transport was increased in the RF and PF groups when compared with the normal control group, suggesting increased permeability to L-ascorbic acid in the former groups. The disparity between in vivo and in vitro results in the RF animals is indicative of some inhibitory influence present in the intact uremic animals. However, experiments comparing the effect of uremic with normal sera on in vitro transport failed to reveal any suppressive effect of uremic chemical environment. In addition, serum ascorbic acid was reduced in PF and RF groups when compared with the normal control animals, thereby excluding elevated blood level as a cause of impaired absorption in intact animals with RF. In conclusion, in vivo jejunal absorption of L-ascorbic acid is impaired in rats with RF despite evidence of increased in vitro permeability. The latter appears to be mediated by reduced nutrient intake and weight loss. The inhibitory influence present in vivo could not be reproduced by incubation with uremic sera in vitro.

Topics: Animals; Ascorbic Acid; Humans; In Vitro Techniques; Intestinal Absorption; Intestinal Mucosa; Kidney Failure, Chronic; Male; Rats; Rats, Inbred Strains

A 55-year-old woman with chronic renal failure treated with hemodialysis had severe bilateral visual loss develop due to retinal ischemia. Ophthalmoscopy showed crystals in the distribution of the retinal arteries, but not veins, and this led to a diagnosis of systemic oxalosis. Factors contributing to systemic oxalosis in addition to renal failure were ascorbic acid dietary supplementation, pyridoxine deficiency, and ileal resection. Histopathologic findings showed ocular calcium oxalate deposition limited nearly entirely to the walls of retinal blood vessels.

Topics: Adult; Ascorbic Acid; Birefringence; Calcium Oxalate; Crystallization; Eye; Fluorescein Angiography; Graft Rejection; Humans; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Renal Dialysis; Retinal Diseases

The present study was undertaken to evaluate the effects of vitamin C supplementation (VC-S) on the morbidity and mortality of 61 clinically stable outpatients maintained on regular hemodialysis (HD). All patients were given vitamin C (500 mg daily) for 2 years and observed for a further 2 years on no treatment. VC-S significantly increased the plasma levels of ascorbic acid up to 7.8 mg/dl (mean 3.3 +/- 0.4 s.e.m.) which fell after withdrawal to the normal range (mean 1.2 +/- 0.2 mg/dl). Hyperoxalemia was aggravated by VC-S (mean 61.5 +/- 3.3 mumol/l, range 33.3 to 165.5) while plasma oxalate levels in the unsupplemented period decreased to 36.3 +/- 3.3 mumol/l (p less than 0.01). There were no differences in creatinine, hematocrit, blood transfusion requirement, morbidity (including hospitalization) or mortality between the two periods of time in the same patients. In conclusion, we could not find any beneficial effects on morbidity or mortality as a result of using VC-S in regular HD patients. However, secondary hyperoxalemia was aggravated. As a result of these observations it appears that VC-S is harmful and unnecessary in these patients provided they are on an adequate diet.

Topics: Ascorbic Acid; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Renal Dialysis; Time Factors

The present study was undertaken to see if the oxalate deposits seen in renal tubules are a causative factor in the development of acquired renal cysts in chronic renal failure. Thirty 5/6 nephrectomized rats had free access to water containing 8 mg/ml of vitamin C (oxalate precursor) and 20 5/6 nephrectomized rats were given tap water without vitamin C. Oxalate deposits were found on microscopy in the renal tubules of vitamin C-treated rats in the 11th and 12th postnephrectomy months; however, acquired renal cysts were noted far in advance of the appearance of oxalate crystals. It has been suggested that the tubular dilatation seen in 5/6 nephrectomized rats is caused by an abrupt decrease in the functioning renal mass, leading to the production of a so-called 'renotropic factor'. However, oxalate deposits and renal tubular dilatation in oxalate-treated 5/6 nephrectomized rats preceded the renal tubular dilatation of untreated partially nephrectomized rats. In addition, these histological changes in the kidney were also seen in healthy rats which were given oxalate orally and subcutaneously. The present study suggested that the pathogenesis of acquired renal cysts is multifactorial. Renotropic factor may play an important role leading to nephron hyperplasia, but oxalate deposits in the renal tubules seem to be an important factor in the formation of these cysts.

Topics: Animals; Ascorbic Acid; Creatinine; Growth Substances; Histocytochemistry; Intercellular Signaling Peptides and Proteins; Kidney Diseases, Cystic; Kidney Failure, Chronic; Kidney Tubules; Nephrectomy; Oxalates; Rats; Rats, Inbred Strains

Oxalate metabolism was studied in ten patients with end-stage renal disease. No patient with primary hyperoxaluria was included in this study. Five patients were on regular haemodialysis and five patients were on chronic ambulatory peritoneal dialysis (CAPD). Oxalate metabolism was assessed by measurement of plasma oxalate concentration (POx), oxalate metabolic pool size (OxMP), tissue oxalate accumulation rate (TOxA), oxalate production rate (OxPR) and dialysis clearance of oxalate (DCOx). These observations were made on three separate occasions in each of the ten patients: initially when the patients were taking a routine ascorbic acid supplement of 100 mg per day; then after a period of 1 month with no ascorbic acid supplement; and then finally after a further period of 1 month's treatment with pyridoxine 800 mg daily. The values for POx, OxMP and TOxA were significantly increased in all ten patients and in the range observed in some patients with type I primary hyperoxaluria. There was no significant difference between immediate prehaemodialysis POx and the POx in the CAPD patients. The DCOx was very much greater during haemodialysis (mean 85 ml/min) than during CAPD (mean 8 ml/min). The acute fall in POx during haemodialysis was greater than 50% of the immediate pre-haemodialysis concentration. Ascorbic acid in a dose of 100 mg/day had no significant effect on the parameters of oxalate metabolism studied. Pyridoxine in a dose of 800 mg/day produced a significant fall in POx in both haemodialysis and CAPD patients.

Topics: Adult; Aged; Ascorbic Acid; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Peritoneal Dialysis, Continuous Ambulatory; Pyridoxine; Renal Dialysis

Topics: Adult; Aged; Ascorbic Acid; Female; Hematopoiesis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory

We report a case of calcium oxalate arthropathy in a woman undergoing intermittent peritoneal dialysis who was not receiving pharmacologic doses of ascorbic acid. She developed acute arthritis, with calcium oxalate crystals in Heberden's and Bouchard's nodes, a phenomenon previously described in gout. Intermittent peritoneal dialysis may be less efficient than hemodialysis in clearing oxalate, and physicians should now consider calcium oxalate-associated arthritis in patients undergoing peritoneal dialysis who are not receiving large doses of ascorbic acid.

Topics: Aged; Arthritis; Ascorbic Acid; Calcium Oxalate; Crystallization; Female; Hand; Humans; Kidney Failure, Chronic; Peritoneal Dialysis; Radiography

A patient with quiescent rheumatoid arthritis, amyloidosis and chronic renal failure developed an inflamed knee. Intracellular bipyramidal crystals characteristic of oxalate were found and are suggested as the cause of the acute arthritis. Since the patient had been treated with vitamin C, this precursor of oxalate is proposed as a possible factor in the crystal deposition.

Topics: Amyloidosis; Arthritis, Rheumatoid; Ascorbic Acid; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Oxalic Acid; Peritoneal Dialysis; Radiography; Synovial Fluid

Topics: Adult; Ascorbic Acid; Calcinosis; Calcium Oxalate; Cardiomyopathies; Humans; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid; Renal Dialysis

Urinary excretion of vitamin C was investigated in 44 patients with chronic renal diseases and in 25 patients after renal transplantation with various mean glomerular filtration rates. In both groups a hyperbolic relationship was observed between FE vitamin C and CCr. In addition, direct relationships were found between FE vitamin C and FE Na, FEK and FE H2O in both groups. Various chronic renal diseases and treatments had no influence on the investigated relationships. In 16 healthy subjects urinary excretion of sodium during maximal water diuresis did not increase but urinary excretion of vitamin C significantly increased. In 10 patients in the polyuric stage of chronic renal failure without dialysis treatment during Giordano-Giovanetti-Maggiora diet with addition of sodium chloride the urinary excretion of sodium increased but that of vitamin C was not influenced. The results obtained for the biochemical parameters tested suggest that the urinary excretion of vitamin C depends on the urinary excretion of water.

Topics: Adult; Ascorbic Acid; Creatinine; Diuresis; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Metabolic Clearance Rate; Potassium; Sodium; Urine

Vitamin supplementation for dialysis patients is still controversial. In our study, we followed longitudinally over a period of a year, 15 patients on chronic hemodialysis who were deprived of vitamin supplementation. Microbiological assays were used to determine the levels of five vitamins of the B group (folate, niacin, B12, B6, and thiamine). Vitamin C was measured chemically. During the observation period when vitamins were not supplemented, a marked drop of many of these vitamins in blood levels were encountered. For vitamins B12 and C, the plasma levels remained within the normal range in all the subjects studied. For the other vitamins, the blood levels were found to be low in a few patients. Our data suggest that vitamin supplementation is probably not needed in most stable hemodialysis patients as it is recommended now, and that perhaps, if supplementation is indicated, less should be given than is presently prescribed. Further research is needed in this area.

Topics: Adult; Aged; Ascorbic Acid; Female; Folic Acid; Follow-Up Studies; Humans; Kidney Failure, Chronic; Longitudinal Studies; Male; Middle Aged; Niacin; Pyridoxine; Renal Dialysis; Thiamine; Vitamin B 12; Vitamins

A continuous flow assay using immobilised oxalate oxidase was used to measure the level of oxalate in plasma ultrafiltrate obtained from healthy subjects and from patients with chronic renal failure. The levels of oxalate in plasma from normal subjects ranged from 1.3-3.1 mumol/l (mean 2.03; SD = 0.52) with females showing a higher (p less than 0.05) level (mean 2.25 mumol/l) than males (mean 1.87 mumol/l). The mean oxalate/creatinine clearance ratio in fourteen healthy subjects was greater than unity, thus indicating a net tubular secretion of oxalate. At physiological pH, L-ascorbate was converted to oxalate in whole blood following venepuncture, in plasma and in plasma ultrafiltrate. Reduction of the spontaneous generation of oxalate in the samples prior to analysis was achieved by acidification and treatment with sodium nitrite. A linear correlation (r = 0.92; p less than 0.001) was found between plasma oxalate and plasma creatinine in patients with chronic renal failure.

Topics: Adult; Ascorbic Acid; Creatinine; Enzymes, Immobilized; Female; Humans; Hydrogen-Ion Concentration; Indicators and Reagents; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid; Oxidoreductases; Reference Values; Sex Factors; Sodium Nitrite; Ultrafiltration

Topics: Adult; Ascorbic Acid; Female; Furosemide; Humans; Kidney Failure, Chronic; Male

Blood concentration of water-soluble vitamins were measured in patients with mild chronic renal insufficiency, uremic undialyzed and dialyzed patients and control subjects. The whole blood concentration of B1 was significantly lower in dialyzed patients. Plasma levels of B2 were elevated in uremic and dialyzed patients and plasma B6 was significantly increased in dialyzed patients. Serum levels of B12 and folic acid were elevated in uremic and dialyzed patients. The results of this study differ from those reported from Europe and the U.S.A. These geographical differences may arise primarily from differences in staple food, vegetable intake, and traditional methods of food preparation.

Topics: Adult; Aged; Ascorbic Acid; Female; Folic Acid; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pyridoxine; Renal Dialysis; Riboflavin; Thiamine; Uremia; Vitamin B 12; Vitamins

99mTc-Phosphomycin, a new radiopharmaceutical for kidney visualization, was used for animal experiments and tests of 171 patients. The results confirmed the usefulness of this product. The ease and yield of the labelling procedure, the low cost of the product, the excellent quality of the images and the functional information obtained showed that the use of 99mTc-phosphomycin as a radiopharmaceutical for kidney visualization has many advantages.

Topics: Adolescent; Adult; Aged; Animals; Anti-Bacterial Agents; Aprotinin; Ascorbic Acid; Chromatography, Paper; Female; Fosfomycin; Humans; Hypertension, Renal; Intestines; Kidney; Kidney Failure, Chronic; Kinetics; Liver; Male; Mice; Middle Aged; Organotechnetium Compounds; Rabbits; Radionuclide Imaging; Technetium; Time Factors

The mean plasma oxalic acid level is increased in renal failure. The mean plasma oxalic acid level was 74.8 +/- 18.5 mumol/l in 15 patients with chronic renal failure and 129.9 +/- 47.7 mumol/l in 31 patients on chronic haemodialysis which are several times higher than the normal range (16.8 +/- 6.0 mumol/l). During haemodialysis oxalic acid showed a behaviour similar to that of creatinine. The increased plasma oxalic acid levels are due to the accumulation of oxalic acid in renal insufficiency and additional metabolic factors increasing endogenous synthesis of oxalic acid. The administration of pyridoxine caused a decrease of the mean plasma oxalic acid level by 46% (32.0 to 56.1%) in 6 out of 8 chronic haemodialysis patients. This occurred most probably by correcting a vitamin B6 deficiency. Investigations of the intraerythrocyte glutamic oxalacetic transaminases showed, that the action of pyridoxine therapy on the endogenous oxalic acid synthesis can be explained by an increase of available pyridoxal-5-phosphate, the active metabolite of vitamin B6. The administration of vitamin B1, however, caused no statistically significant decrease of the plasma oxalic acid levels. Other influences on plasma oxalic acid synthesis result from the diminished excretion of the precursors of oxalic acid glycolic acid and ascorbic acid. The conversion of glycolic acid to glycine is probably increased in uraemia. The administration of 1 g ascorbic acid after each haemodialysis caused a striking increase of the plasma oxalic acid levels up to 240% of the initial value within 2 weeks, as a consequence of an increased metabolism of accumulated ascorbic acid. Increased plasma oxalic acid levels seem to be an important factor for calcium oxalate deposits in uraemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Ascorbic Acid; Aspartate Aminotransferases; Combined Modality Therapy; Erythrocytes; Glycolates; Humans; Kidney Failure, Chronic; Kidney Function Tests; Oxalates; Oxalic Acid; Pyridoxine; Renal Dialysis; Thiamine; Uremia

Topics: Adult; Ascorbic Acid; Female; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male

We studied vitamin C levels in 25 stable patients on chronic hemodialysis who were taking 0.5-1 g vitamin C orally daily and/or dialyzed against dialysate containing 33.3 micrograms/ml of vitamin C. We also studied the relationship between serum vitamin C and oxalate levels in 7 patients on chronic hemodialysis. All patients had markedly elevated pre- and postdialysis levels of vitamin C. The predialysis levels of vitamin C showed extremely good correlation to the serum oxalate levels. Overingestion of vitamin C in food or as supplementation may lead to excessive serum levels of vitamin C, resulting in hyperoxalemia that may contribute to vascular disease in patients on chronic hemodialysis.

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Child; Humans; Kidney Failure, Chronic; Middle Aged; Oxalates; Oxalic Acid; Renal Dialysis

Topics: Adult; Ascorbic Acid; Binding, Competitive; Calcitonin; Carcinoma; Humans; Kidney Failure, Chronic; Radioimmunoassay; Thyroid Neoplasms; Urea

Deficiencies of water-soluble vitamins may occur in uremic patients mainly because of restricted consumption and of loss during chronic hemo- and peritoneal dialysis. Although the daily requirement for most vitamins is not well defined in chronic renal failure supplementation of the vitamins thiamine, riboflavin, pyridoxine, pantothenic acid, niacin and ascorbic acid, the form of one multivitamin preparation without vitamin A as well as folic acid in dialysis patients after each dialysis is recommended. There is no need for vitamin B12, vitamin A and vitamin E.

Topics: Ascorbic Acid; Avitaminosis; Biotin; Folic Acid; Humans; Kidney Failure, Chronic; Niacin; Pantothenic Acid; Pyridoxine; Riboflavin; Thiamine; Vitamin A; Vitamin B 12; Vitamin E; Vitamin K; Vitamins

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid; Renal Dialysis

Topics: Aged; Ascorbic Acid; Humans; Infusions, Parenteral; Kidney Failure, Chronic; Male

Topics: Ascorbic Acid; Female; Humans; Kidney Failure, Chronic; Leukocytes; Male; Middle Aged

In 10 patients who had been on CAPD for 8.75 months, blood levels of the vitamins A, E, B-complex and C were measured and a precise diet history using food weighing for 3 days was obtained. Plasma vitamin A was elevated in all; since retinol binding protein (RPB) was elevated even more, the ratio of retinol to RBP was low. Vitamin E levels were also high. The vitamins B1, B2 and B6 were measured using erythrocyte enzyme activities. Vitamin B1 was low or borderline in 5, vitamin B6 was decreased in 3 and erythrocyte pyridoxal phosphate in 8 patients. Folic acid was low or borderline in 6 patients, whereas the vitamins B2 and B12 were normal in all. Vitamin C was diminished in 4 patients, and in dialyzate 60% of plasma concentrations were found. The intakes of the vitamins B1, B6 and B12 were below the recommended range. After supplementation of water soluble vitamins for 7 weeks the vitamins A and E remained elevated and B1 remained low, B6 and C had normalized in all and folic acid was markedly elevated. In CAPD decreased blood concentrations of some water soluble vitamins are found due to insufficient dietary intake and loss into dialyzate. Tentative recommendations are given for the replacement of the vitamins B1, B6, folic acid and C.

Topics: Adult; Aged; Ascorbic Acid; Avitaminosis; Energy Intake; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Thiamine; Vitamin B Complex; Vitamin E

Topics: Ascorbic Acid; Humans; Kidney Failure, Chronic; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory

Topics: Adolescent; Adult; Aged; Anemia; Ascorbic Acid; Chloramines; Female; Filtration; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Water Pollutants; Water Pollutants, Chemical

Topics: Adult; Ascorbic Acid; Calcitonin; Goiter, Nodular; Humans; Kidney Failure, Chronic; Radioimmunoassay

Topics: Ascorbic Acid; Female; Humans; Infant; Kidney Failure, Chronic; Nephrotic Syndrome

The requirements of healthy people for nutrients are constantly being monitored and updated. The most recent publication for the United States is the 9th ed. of the Recommended Dietary Allowances handbook. This article comments on changes that have been made and examines the relevance of such allowances for the long-term nutritional well-being of patients with renal disease. Different aspects of the allowances for energy, protein, vitamin C, calcium, iron, and trace elements are discussed to illustrate uses and limitations of dietary allowances and to emphasize the significance of this information for the better nutrition of the renal patient.

Topics: Adult; Age Factors; Aged; Ascorbic Acid; Basal Metabolism; Diet; Dietary Proteins; Energy Intake; Energy Metabolism; Health; Humans; Infant; Iron; Kidney Failure, Chronic; Middle Aged; Nutritional Physiological Phenomena; Nutritional Requirements; Trace Elements; United States

Topics: Adult; Anemia, Hemolytic; Ascorbic Acid; Female; Hemolysis; Humans; Hypochlorous Acid; Japan; Kidney Failure, Chronic; Male; Renal Dialysis; Water Supply

Blood concentrations of water soluble vitamins were studied in 29 undialyzed and 35 dialyzed patients with CRF, and 36 healthy volunteers. Effects of B6 administration on immunological parameters were studied in dialyzed patients. In dialyzed patients, whole blood B1 decreased, while plasma B2, B6 and serum B12 and folic acid increased. In undialyzed patients with uremia, plasma B2, serum B12 and folic acid increased, while plasma C decreased in patients with moderate CRF. Oral administration of B6 for 4 wks was associated with improved tuberculin skin tests and PHA mitogen responses in dialyzed patients. Supplementation of B1 is required for patients with CRF while B6 and C may be considered.

Topics: Ascorbic Acid; Folic Acid; Humans; Kidney Failure, Chronic; Lymphocytes; Pyridoxine; Renal Dialysis; Riboflavin; Thiamine; Tuberculin Test; Vitamin B 12; Vitamins

Chloramines, compounds made up of chlorine and ammonia, when present in tap water used for dialysis cause methemoglobinemia and hemolysis. Ascorbic acid addition has been reported to effectively neutralize chloramines in vitro and in patients dialyzed with the single batch dialysis delivery system. We extended these observations to patients dialyzed with the proportioning dialysis delivery system where exposure time of ascorbic acid to chloramines is shorter. This may be important since we found that the half time of the reaction between ascorbic acid and chloramines is 4 minutes. Red cell oxidant sensitivity in 15 patients was assessed by incubating red cells with ascorbate-cyanide and measuring methemoglobin which averaged 2.17 +/- 0.42 g/100 ml (SEM) before dialysis and 2.87 +/- 0.52 g/100 ml after dialysis (NS). Reduced glutathione (GSH) levels were also measured as an index of red cell oxidant damage. GSH decreased from a mean of 7.40 +/- 0.59 micromoles/g Hb before dialysis to 6.98 +/- 0.52 micronmoles/g Hb after dialysis (P less than 0.01). In 2 patients there was no change in 51Cr red cell survival when dialyzed on either the proportioning system or other chloramine free systems. We conclude that addition of ascorbic acid to neutralize chloramines in tap water is also effective when using the proportioning dialysis delivery system.

Topics: Adult; Aged; Ascorbic Acid; Chloramines; Erythrocyte Aging; Glutathione; Hemolysis; Humans; Kidney Failure, Chronic; Methemoglobin; Methemoglobinemia; Middle Aged; Renal Dialysis

Topics: Adult; Ascorbic Acid; Female; Humans; Kidney Failure, Chronic; Male; Renal Dialysis

In two dialysis centres in the same city, with a total of 56 patients on regular dialysis treatment, it has been shown that the tap water used for the production of the dialysate contains chloramines. Total chlorine concentration and percentage of chloramines varies from 0.5 to 1.1 ppm and from 40 to 95 per cent. There in a high percentage of Heinz bodies in the patients' erythrocytes, and incubation of red cells in vitro with the dialysate raises the methaemoglobin concentration and alters the hexose-monophosphate shunt. The patients' mean haematocrit improved from 23.13 +/- 4.41 SD to 25.93 +/- 5.17 SD (p less than 0.0025) with the administration of ascorbic acid, 500 mg given intravenously once a week, but an unexpected transitory increase of the total chlorine to 3.5 ppm resulted in a serious decline of the mean haematocrit to 20.80 +/- 5.22 SD (p less than 0.0001). Ascorbic acid added to the dialysate at a concentration of 1.7 mg/dl produced a great improvement in the anaemia and the almost total disappearance of Heinz bodies from the patients' red cells.

Topics: Anemia; Ascorbic Acid; Chloramines; Heinz Bodies; Hematocrit; Humans; Kidney Failure, Chronic; Renal Dialysis; Water Supply

Topics: Ascorbic Acid; Humans; Kidney Failure, Chronic; Solubility; Vitamins

Topics: Adolescent; Adult; Ascorbic Acid; Female; Heparin Antagonists; Humans; Kidney Failure, Chronic; Male; Renal Dialysis

Topics: Ascorbic Acid; Humans; Kidney Failure, Chronic; Renal Dialysis; Time Factors

Topics: Adult; Ascorbic Acid; Blood Cell Count; Creatinine; Female; Folic Acid; Hematocrit; Hemoglobinometry; Humans; Kidney Failure, Chronic; Male; Methemoglobin; Middle Aged; Neural Conduction; Nitrofurantoin; Peripheral Nerves; Reticulocytes; Urinary Tract Infections

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Diet Therapy; Humans; Kidney Failure, Chronic; Long-Term Care; Renal Dialysis

Topics: Ascorbic Acid; Diet; Humans; Intestinal Absorption; Kidney Failure, Chronic; Renal Dialysis

Topics: Acidosis, Renal Tubular; Adult; Aluminum; Ascorbic Acid; Bone Diseases; Calcium; Calcium Metabolism Disorders; Female; Humans; Hyperparathyroidism; Kidney Diseases; Kidney Failure, Chronic; Osteitis Fibrosa Cystica; Osteomalacia; Vitamin D; Vitamin D Deficiency