The excretion of ascorbic acid and its metabolites in uremia and hemodialysis

Renal excretion of ascorbic, dehydroascorbic and diketogulonic acids in uremia and relevant loss in hemodialysis are measured in comparison with those in patients with uremic syndrome (prior to hemodialysis) and in healthy subjects (control). Renal elimination of ascorbic acid was higher while of dehydroascorbic acid lower vs control. Elimination of diketogulonic acid was similar to control. In a session of hemodialysis, the organism loses 132.0 +/- 13.6 mg of ascorbic, 132.0 +/- 10.0 mg of dehydroascorbic and 204.0 +/- 9.0 mg of diketogulonic acid. 48-hour urinary losses of the patients reached 8.4 +/- 1.4, 19.6 +/- 1.1, 75.6 +/- 1.5 mg, respectively. Compared to control, hemodialysis patients lose the above acids 24.3, 2.7 and 4.6 times more.     

Serum ascorbic acid in patients undergoing chronic hemodialysis

Serum presupplementation ascorbic acid levels were subnormal in 8 out of 10 patients undergoing chronic hemodialysis with capillary film and capillary flow dialyzers, the mean duration of treatment being 11 months. Supplementation with 100 mg ascorbic acid daily for two weeks raised the ascorbic acid values to normal in 9 out of 10 patients. After supplementation with 500 mg daily, all patients had ascorbic acid levels exceeding the normal upper limit, and 3 of them had gastrointestinal side-effects. The mean blood pH value, measured in 24 patients on chronic hemodialysis, showed a significant, though slight, decrease during supplementation with 500 mg daily as compared with the mean presupplementation value, but no statistically significant changes were observed in blood bicarbonate, base excess or PCO2 values.     

Excessive myocardial calcinosis in a chronic hemodialyzed patient

Summary Secondary oxalosis in chronic hemodialyzed patients is caused by impaired renal excretion and inadequate removal of oxalic acid during hemodialysis. Ascorbic acid is a precursor of oxalic acid. We report a parathyroidectomized patient with chronic renal failure, on hemodialysis, who received over a period of several months a total dose of 91.0 g ascorbic acid i.v. The plasma oxalic acid level in this patient was 14-fold higher than in healthy persons. Increased oxalic acid synthesis from its precursor ascorbic acid may be responsible for hyperoxalemia, high content of oxalic acid in myocardium, aorta and lung, and calcium oxalate deposition in soft tissues. Application of high doses of ascorbic acid should be avoided in hemodialysed patients with chronic renal failure.Abbreviations PTH parathyroid-hormone - RDT regular dialysis treatment     

Effect of ascorbic acid deficiency on serum ferritin concentration in patients with beta-thalassaemia major and iron overload.

The incidence of ascorbic acid (AA) deficiency and its effect on serum ferritin concentration relative to body iron stores was studied in 61 unchelated patients with beta-thalassaemia major. Thirty-nine (64%) of patients had subnormal leucocyte ascorbate concentrations without clinical evidence of scurvy. The lowest leucocyte ascorbate concentrations tended to occur in the most transfused patients. No correlation was found between the units transfused and serum ferritin concentration in the AA-deficient patients but a close correlation (r = +0.82; p less than 0.005) existed for the AA-replete group. Similarly a close correlation (r = +0.77; p less than 0.005) was obtained between liver iron concentration and serum ferritin in AA-replete patients but only a weak correlation (r = +0.385; p less than 0.025) existed for the AA-deficient group. When AA-deficient patients were treated with ascorbic acid, serum iron and percentage saturation of iron binding capacity rose significantly; serum ferritin rose in 13 of 21 patients despite the simultaneous commencement of desferrioxamine therapy. In contrast all three measurements tended to fall in AA-replete patients with ascorbic acid and desferrioxamine therapy. Thus, AA deficiency is commonly present in beta-thalassaemia patients with iron overload and may give rise to inappropriate serum ferritin concentrations in relation to body iron stores.     

Lack of oxidative damage in serum polyunsaturated fatty acids before and after dialysis in chronic uremic patients

We described previously that in the erythrocytes and mononuclear blood cells from uremic patients on chronic hemodialysis, the membrane concentrations of malonyldialdehyde (MDA), resulting from peroxidation of polyunsaturated fatty acids (PUFA) in the membrane itself increased, and the concentrations of vitamin E (VIT E), the major antioxidizing agent, were lower. In the present study we analysed whether similar oxidative damage is seen in the serum from hemodialysis patients and whether the serum fatty acid pattern is affected. No evidence was found of oxidative damage in the serum during hemodialysis, serum concentrations of MDA and VIT E remaining constant before and after dialysis. No change was observed in serum pattern of PUFA, particularly linoleic acid. We therefore assume that the oxidative damage described in uremic patients is mainly intracellular.     

Molecular analysis of extracellular-superoxide dismutase gene associated with high level in serum

Summary Extracellular-superoxide dismutase (EC-SOD) is one of the SOD isozymes mainly distributed in the extracellular fluid. In the vascular system, it is located on the endothelial cell surface according to studies on the heparin binding capacity. By measurement of serum EC-SOD levels of Japanese in healthy persons (n=103) and hemodialysis patients (n=150), 7 healthy subjects and 24 hemodialysis patients were classified into group II associated with high EC-SOD levels. By molecular analysis of the EC-SOD coding region from the group II individuals in Sweden, a single nucleotide substitution of G to C generating an amino acid change of arginine to glycine has been identified in the region associated with the heparin affinity of the enzyme. The same mutation was detected in the Japanese as a homozygote in both alleles of 2 hemodialysis patients and as a heterozygote in one allele of all the healthy group II individuals and 17 hemodialysis patients. The amino acid substitution may result in the decrease of the heparin affinity which is favorable for the existence of EC-SOD in the serum.     

Effect of ascorbic acid on the serum folic acid estimation

Ascorbic acid added to the basal medium increased the growth response of Lactobacillus casei in folic acid standards. The effect in the serum extracts was not marked, resulting in lowered serum folic acid estimations. However, results obtained on prolonged incubation were similar whether ascorbic acid was added or not. The presence or absence of ascorbic acid and variation of the incubation period may account for differences in reported normal ranges of serum folic acid levels.     

Serum Stimulation of Lysyl Hydroxylase Activity in Cultured Human Skin Fibroblasts

In the absence of ascorbic acid, confluent human skin fibroblasts incubated in 0. 5% serum-supplemented medium had one-third of the level of lysyl hydroxylase activity of cells incubated in media containing high serum concentrations (5-20%). This difference appeared to be due to a decline in the enzyme activity following serum deficiency, and was largely abolished by addition of ascorbic acid to the medium. The effect of serum deficiency was slow, manifesting in 48 h at the earliest, and was completely reversed by replenishing the medium with serum. Prolyl hydroxylase activity was independent of serum concentration, both in the absence and in the presence of ascorbic acid in the culture medium.     

Serum stimulation of lysyl hydroxylase activity in cultured human skin fibroblasts

In the absence of ascorbic acid, confluent human skin fibroblasts incubated in 0.5% serum-supplemented medium had one-third of the level of lysyl hydroxylase activity of cells incubated in media containing high serum concentrations (5-20%). This difference appeared to be due to a decline in the enzyme activity following serum deficiency, and was largely abolished by addition of ascorbic acid to the medium. The effect of serum deficiency was slow, manifesting in 48 h at the earliest, and was completely reversed by replenishing the medium with serum. Prolyl hydroxylase activity was independent of serum concentration, both in the absence and in the presence of ascorbic acid in the culture medium.     

Ascorbic acid-induced regression of amyloidosis in experimental animals

Ascorbic acid was found to accelerate amyloid degradation in an experimental animal model. Based on experiments in vitro which demonstrated the ability of ascorbic acid to restore the amyloid-degrading activity of amyloidotic human serum, the effect of orally administered ascorbic acid was tested in casein-induced murine amyloidosis. Histopathological examination of splenic tissue of mice killed at different times after the termination of the amyloidogenic stimulus showed a markedly decreased amyloid deposition in ascorbic acid-treated animals as compared to the controls. The effect of ascorbic acid was to a certain degree dose-dependent. Colchicine blocked amyloid synthesis when administered during amyloid induction. In animals which were given the drug during the post-induction period it had no effect. The amyloid-degrading activity of mouse serum was reduced in amyloidotic mice. Administration of ascorbic acid partially restored the amyloid-degrading activity of these animals.     

Ascorbic acid-induced regression of amyloidosis in experimental animals.

Ascorbic acid was found to accelerate amyloid degradation in an experimental animal model. Based on experiments in vitro which demonstrated the ability of ascorbic acid to restore the amyloid-degrading activity of amyloidotic human serum, the effect of orally administered ascorbic acid was tested in casein-induced murine amyloidosis. Histopathological examination of splenic tissue of mice killed at different times after the termination of the amyloidogenic stimulus showed a markedly decreased amyloid deposition in ascorbic acid-treated animals as compared to the controls. The effect of ascorbic acid was to a certain degree dose-dependent. Colchicine blocked amyloid synthesis when administered during amyloid induction. In animals which were given the drug during the post-induction period it had no effect. The amyloid-degrading activity of mouse serum was reduced in amyloidotic mice. Administration of ascorbic acid partially restored the amyloid-degrading activity of these animals.     

Homeostasis of antioxidant status in hemodialysis patients]

Oxidative stress, which occurs when there is excessive free-radical production or low antioxidant levels, makes significant contributions to pathogenesis in many human diseases. Cardiovascular disease is the major cause of mortality in patients receiving hemodialysis. For these patients, oxidative stress and increased lipid peroxidation may contribute to increased risk of atherosclerosis. The aim of this study was to determine if hemodialysis patients were associated with disturbance of homeostasis of antioxidant status. In this experiment, total antioxidant status of serum is measured by its ability to inhibit generation of free radicals from 2,2'-amino-di-[3-ethylbenzthiazole sulphonate] by metmyoglobin and hydrogen peroxide. Status of radical scavengers, such as serum total protein, albumin, uric acid and total bilirubin, was also measured. Blood were collected from three different episodes of hemodialysis. In the first group (n = 29), blood were collected before and after hemodialysis. In the second group (n = 29), blood were collected after dialysis and before next hemodialysis. In the third group (n = 8), blood were collected before hemodialysis. After last hemodialysis, patients started ingesting vitamin C and blood were collected before next hemodialysis. There was a marked reduction of total antioxidant status after hemodialysis in the first group. There was a marked increase in total antioxidant status before next hemodialysis in the second group. High doses of vitamin C caused increase in total antioxidant status in the third group. In conclusion, disturbance of homeostasis of total antioxidant status were observed in patients receiving hemodialysis. This may play a role in the pathogenesis in these groups.     

Ineffectiveness of ascorbic acid therapy in nephropathic cystinosis.

Because high concentrations of ascorbic acid (0.57 mM) lower the free (nonprotein) cystine content of cultured cystinotic skin fibroblasts by over 50 per cent, we did a double-blind clinical trial to establish whether this drug would benefit cystinotic children. Sixty-four patients were randomized into the study; 32 received ascorbic acid (200 mg per kilogram of body weight per day), and 32 placebo. The study was terminated after approximately two years because there was no indication that vitamin C was beneficial and accumulating evidence that it might be harmful. Of 11 patients who left the study because of death or the requirement for dialysis or renal transplantation, eight were receiving ascorbic acid. The estimated relative risk (treatment vs. control) of an adverse event was R = 2.7, with a 90 per cent confidence interval of (0.8, 11.5). The serum creatinine concentration increased 0.53 mg per deciliter per year in patients receiving vitamin C and 0.24 mg per deciliter per year in patients receiving placebo (P = 0.08).     

心钠素和甲状旁腺素对血液透析低血压的影响

为探讨血透患者血清心钠素(ANF)和甲状旁腺素(iPTH)水平与血液透析低血压的关系, 采用放射免疫分析和免疫放射分析法分别测定36例维持性血透患者透析前后血清ANF和iPTH水平变化, 并分析其与低血压的关系. 结果发现: 血透患者ANF和iPTH总体水平显著高于对照组, 透析后总体水平显著低于透析前(P均小于0.01); 低血压组患者透析前血清ANF和iPTH水平均高于正常血压组(P均小于0.05); 透析后低血压组患者ANF水平较透析前显著降低(P＜0.05),但iPTH水平较透析前进一步增高(P＜0.05).结论: 血透中发作性低血压与患者血清ANF和iPTH水平升高有一定联系.     

Blood cholesterol profile in guineapigs: Effect of ascorbic acid ingestion on hypercholesterolemia induced by manganese deficiency or overdosage of an anti-thyroid agent in diet

Effects of ascorbic acid ingestion (0.25 g/day) on serum cholesterol and total lipid levels were compared in three hyperlipidemic guineapig models. The first model received a diet rich in atherogenic and thrombogenic agents (e.g. cholesterol, butter-fat, cholic acid, vitamin D₂ etc.). The second (hypothyroid) and third (deficient manganese) models were created by feeding excess propyl-thiouracil (a potent goitrogen) and low-level manganese without added dietary cholesterol. The extreme rapidity with which guineapigs of Wistar strain develop hypercholesterolemia and early atherosclerotic lesions makes them an attractive animal model for studying the early development of atherosclerosis in man.

Decreased serum and tissue cholesterol levels despite more dietary cholesterol and butter-fat indicate that ascorbic acid is a good hypolipidemic/hypocholesterolemic agent. As the lipid-lowering property of ascorbic acid is obliterated due to hypothyroidism, it is most probable that vitamin C may act through the thyroid gland. Interaction with thyroid hormones seems not unlikely for ascorbic acid under physiological conditions. Since ascorbic acid has been suggested to provide protection against atherosclerosis induced by atherogenic/thrombogenic agents and proved incoherent in the face of thyroid dysfunction and manganese deprivation, the precise relation of these effects to lipid metabolism warrants investigation in some other fields.     

红光照射对维持性血液透析患者血磷影响的研究

目的 评估血液透析时用红光照射方法来降低血磷的效果.方法 选取60例维持性血液透析患者,分为治疗组和对照组.在进行血液透析治疗期间,采用MRX-1体外红光治疗系统照射治疗组患者体外循环管中的血液,每次照射时间持续60 min,以10次照射为一疗程;对照组患者则仍按照常规方法进行血液透析治疗.对两组患者在治疗前后均抽血测定血磷水平.结果 治疗组的30例患者透析失衡综合征症状减轻;治疗组与对照组患者在血液透析前的血磷水平差异无统计学意义(P＞0.05),而在透析后2组的血磷水平差异有统计学意义(P＜0.05).结论 对维持性血液透析患者而言,进行血液透析时用红光照射体外循环血液能够很好地起到降低血磷的效果.     

Correlation of serum magnesium with dyslipidemia in maintenance hemodialysis patients

One of the factors involved in accelerated atherosclerosis in hemodialysis patients is dyslipidemia. In this study we considered factors involved in intensification of dyslipidemia in hemodialysis patients. This study was done on 36 maintenance hemodialysis patients. Serum lipoprotein (a), Triglyceride, Cholesterol, HDL-C,LDL-C and also serum Intact parathormone(iPTH), Calcium, Phosphorus, Magnesium were measured. In statistical analysis there was not any correlation between serum lipids and iPTH. There was not correlation between serum calcium with serum lipids (p > 0.05). There was not correlation between CaxP product with serum lipids (p > 0.05). There was a positive correlation between serum Magnesium and Lipoprotein(a) (P < 0.05) and also positive correlation between serum magnesium with triglyceride level (P < 0.05) was seen too. Magnesium doesn't increase the lipoprotein synthesis. It may involve in the regulation of some enzymes responsible for lipoprotein synthesis. Correlation of serum magnesium with serum triglycerides can be due to changes in hepatic triglyceride metabolism. Lipoprotein(a) is a non traditional factor of premature atherosclerosis, its association with serum magnesium needs more attention in hemodialysis patients.     

Ascorbic acid alleviates pancreatic damage induced by dibutyltin dichloride (DBTC) in rats

PURPOSE: Because previous studies have reported depleted antioxidant capacity in patients with chronic pancreatitis (CP), prevention of free radical production has gained importance in antifibrotic treatment strategies for CP. The aim of this study was to investigate the effects of ascorbic acid on oxidative capacity and pancreatic damage in experimental CP. MATERIALS AND METHODS: CP was induced in male Sprague-Dawley rats by infusion of dibutyltin dichloride (DBTC) into the tail vein. Ascorbic acid was given intraperitoneally at a daily dose of 10 mg/kg body weight. The treatment groups were as follows: group 1, DBTC plus intraperitoneal physiologic saline; group 2, DBTC plus intraperitoneal ascorbic acid; group 3, solvent plus intraperitoneal physiologic saline; group 4, no operation plus intraperitoneal physiologic saline. Each group contained 15 animals. Treatment was started after CP was established. After 4 weeks of treatment, serum hyaluronic acid and laminin levels were determined by radioimmunoassay, pancreatic tissue oxidative stress was analyzed, and the degree of pancreatic damage was determined. RESULTS: Ascorbic acid treatment markedly increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) concentrations in pancreatic tissue (p < 0.01 for both). Significant serum hyaluronic acid and laminin reductions were observed in group 2 as compared with group 1 (p < 0.05). However, the serum hyaluronic acid and laminin levels remained elevated when compared with those of groups 3 and 4 (p < 0.05). Histopathologic scores were also lower in animals with CP that underwent ascorbic acid-treatment (p < 0.05). CONCLUSION: Ascorbic acid treatment alleviated the degree of oxidative stress and pancreatic damage in rat CP. Antioxidant treatment might be considered a potential option to improve the pathologic process in CP.     

Impact of long-term hemodialysis on nutritional status in patients with end-stage renal failure

We evaluated the way in which duration of hemodialysis treatment affects nutritional status in 96 end-stage renal failure patients. According to the length of previous hemodialysis treatment patients were divided into the groups: onset hemodialysis (ON-HD), early-stage hemodialysis (ES-HD, 1–8 months), mid-stage hemodialysis (MS-HD, 9–69 months), and advanced-stage hemodialysis (ASHD, 70–207 months). Nutritional status was assessed by laboratory data (serum proteins, total lymphocyte count), intradermal skin antigen testing, anthropometric measurements (body mass index [BMI], infrared interactance), and records of food intake. ON-HD patients on a low-protein diet exhibited abnormally low values for serum total protein, albumin, transferrin, and total lymphocyte count and a high prevalence of anergy to skin antigens (69%). In the ES-HD and MS-HD groups values for serum proteins and total lymphocyte count were in the normal range and significantly higher than in ON-HD patients. In addition, a lower proportion of cutaneous anergy was observed (50% and 27%, respectively). Long-term hemodialysis therapy for 6–17 years (AS-HD) was associated with normal levels for all measured serum proteins. Subnormal levels of total lymphocyte count, significantly lower than in MS-HD patients, were associated with an increase in anergy to skin antigens (46%). Serum prealbumin, complement C3c, BMI, body fat, and lean body mass exhibited normal values in all patients and showed no differences between groups. These results indicate that diminished visceral protein stores, lymphopenia, and anergy to skin antigens are widespread in undialyzed uremic patients with end-stage renal failure but become uncommon after the initiation of regular hemodialysis therapy. Even patients on long term hemodialysis for 6–17 years can maintain their serum protein levels, BMI, body fat, and lean body mass in the normal range. The catabolic stimulus of the dialysis procedure itself does not seem to outweigh its beneficial effect of removing uremic toxins when patients are treated for so many years. The occurrence of lymphopenia and a higher proportion of anergy to skin antigens in AS-HD patients indicates that hemodialysis treatment of very long duration has a depressive effect on immunological functions, but not on nutritional status.Abbreviations ON-HD onset hemodialysis - ES-HD earlystage hemodialysis - MS-HD mid-stage hemodialysis - AS-HD advanced-stage hemodialysis - BMI body mass index Correspondence to: P. Kaufmann     

慢性肾功能衰竭患者血透前后血浆leptin和NPY检测的临床意义

目的：探讨了慢性肾功能衰竭患者血透前后血浆leptin和NPY水平的变化及意义。方法：应用放射免疫分析对31例慢性肾功能衰竭患者进行了血透前后血浆leptin和NPY水平的变化,并与35名正常健康人作比较。结果：慢性肾功能衰竭患者在血透前血浆leptin和NPY水平非常显著地高于正常人组（P〈0.01）,血透后1周与正常人组比较仍有显著性差异（P〈0.05）。结论：慢性肾功能衰竭患者存在高leptin和NPY血症,血透有增加leptin和NPY的消除率,具有重要的临床价值。