ascorbic-acid and Hyperoxaluria

Topics: Ascorbic Acid; Humans; Hyperoxaluria; Kidney; Kidney Diseases; Kidney Transplantation; Oxalates

With the increased use of nonprescription vitamin supplementation, physicians involved in critical care must be aware of the potential complications of these medications. We report the case of a 31-year-old African-American man presenting to the emergency department with acute renal failure. He had previously been well and initially denied the use of any drugs except for vitamin C tablets obtained at a local health food store. This case report and review of the literature is utilized to illustrate the importance of historical data in patients presenting with acute renal failure to a critical care service.

Topics: Acute Kidney Injury; Adult; Antioxidants; Ascorbic Acid; Biopsy; Blood Urea Nitrogen; Dietary Supplements; Humans; Hyperoxaluria; Male; Nonprescription Drugs; Renal Dialysis

The reactions that culminate in the synthesis of oxalate in human cells have not yet been clarified. Glycolate and glyoxylate appear to be major precursors. Experimental problems and unresolved issues are highlighted in this review. Assumptions that have been made with out experimental support are identified. The recognition of these assumptions and the testing of their validity should advance our knowledge of the pathways involved, their regulation, and their physiologic significance.

Topics: Ascorbic Acid; Glycolates; Glyoxylates; Humans; Hyperoxaluria; Models, Biological; Oxalates

Topics: Ascorbic Acid; Diet; Glyoxylates; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Intestinal Absorption; Kidney; Metabolism, Inborn Errors; Oxalates

Ascorbic acid is frequently administered intravenously by alternative health practitioners and, occasionally, by mainstream physicians. Intravenous administration can greatly increase the amount of ascorbic acid that reaches the circulation, potentially increasing the risk of oxalate crystallization in the urinary space. To investigate this possibility, we developed gas chromatography mass spectrometry methodology and sampling and storage procedures for oxalic acid analysis without interference from ascorbic acid and measured urinary oxalic acid excretion in people administered intravenous ascorbic acid in doses ranging from 0.2 to 1.5 g/kg body weight. In vitro oxidation of ascorbic acid to oxalic acid did not occur when urine samples were brought immediately to pH less than 2 and stored at -30 degrees C within 6 hours. Even very high ascorbic acid concentrations did not interfere with the analysis when oxalic acid extraction was carried out at pH 1. As measured during and over the 6 hours after ascorbic acid infusions, urinary oxalic acid excretion increased with increasing doses, reaching approximately 80 mg at a dose of approximately 100 g. We conclude that, when studied using correct procedures for sample handling, storage, and analysis, less than 0.5% of a very large intravenous dose of ascorbic acid is recovered as urinary oxalic acid in people with normal renal function.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Calcium Oxalate; Female; Humans; Hyperoxaluria; Injections, Intravenous; Male; Middle Aged; Neoplasms; Oxalic Acid; Urinary Calculi

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

Currently, the recommended upper limit for ascorbic acid (AA) intake is 2000 mg/d. However, because AA is endogenously converted to oxalate and appears to increase the absorption of dietary oxalate, supplementation may increase the risk of kidney stones. The effect of AA supplementation on urinary oxalate was studied in a randomized, crossover, controlled design in which subjects consumed a controlled diet in a university metabolic unit. Stoneformers (n = 29; SF) and age- and gender-matched non-stoneformers (n = 19; NSF) consumed 1000 mg AA twice each day with each morning and evening meal for 6 d (treatment A), and no AA for 6 d (treatment N) in random order. After 5 d of adaptation to a low-oxalate diet, participants lived for 24 h in a metabolic unit, during which they were given 136 mg oxalate, including 18 mg 13C2 oxalic acid, 2 h before breakfast; they then consumed a controlled very low-oxalate diet for 24 h. Of the 48 participants, 19 (12 stoneformers, 7 non-stoneformers) were identified as responders, defined by an increase in 24-h total oxalate excretion > 10% after treatment A compared with N. Responders had a greater 24-h Tiselius Risk Index (TRI) with AA supplementation (1.10 +/- 0.66 treatment A vs. 0.76 +/- 0.42 treatment N) because of a 31% increase in the percentage of oxalate absorption (10.5 +/- 3.2% treatment A vs. 8.0 +/- 2.4% treatment N) and a 39% increase in endogenous oxalate synthesis with treatment A than during treatment N (544 +/- 131 A vs. 391 +/- 71 micromol/d N). The 1000 mg AA twice each day increased urinary oxalate and TRI for calcium oxalate kidney stones in 40% of participants, both stoneformers and non-stoneformers.

Topics: Adult; Ascorbic Acid; Body Mass Index; Body Weight; Calcium; Calcium Oxalate; Cross-Over Studies; Female; Humans; Hyperoxaluria; Kidney Calculi; Male; Oxalates; Reference Values; Risk Factors

To investigate the oxalate intake and the effect of an oxalate load on urinary oxalate excretion in calcium stone-forming (CSF) patients.. Prospective study.. University-affiliated outpatient Renal Lithiasis Unit.. Seventy (70) CSF and 41 healthy subjects (HS) collected a 24-hour urine sample and were submitted to a 3-day dietary record to determine mean oxalate (Ox), calcium (Ca) and vitamin C intake. Fifty-eight (58) CSF patients were randomly selected to receive milk (N = 28) or dark (N = 30) chocolate as an oxalate load.. Administration of either milk (94 mg Ox + 430 mg Ca) or dark chocolate (94 mg Ox + 26 mg Ca) for 3 days. A 24-hour urine sample was obtained before and after the load to determine calcium, oxalate, sodium, potassium, urea, and creatinine.. Oxalate intake and excretion.. CSF patients presented mean Ox intake of 98 +/- 137 mg/d, similar to that of HS (108 +/- 139 mg/d). Mean Ox and vitamin C intake was directly correlated with Ox excretion only in CSF. The consumption of dark chocolate induced a significant increase in mean urinary Ox (36 +/- 14 versus 30 +/- 10 mg/24 hr) not observed in the milk chocolate group. Thus, a 2-fold increase in Ox intake in this population of CSF patients produced a significant 20% increase in oxaluria, not observed when Ca was consumed simultaneously.. The present study suggests that even small increases in Ox intake affect oxalate excretion and the mitigation of urinary oxalate increase by Ca consumption reinforces that Ca and Ox intakes for CSF patients should be in balance. Further studies are necessary to assess whether or not a 20% increase in oxaluria will lead to a higher risk of stone formation.

Topics: Adult; Animals; Ascorbic Acid; Cacao; Calcium; Calcium, Dietary; Diet Records; Female; Humans; Hyperoxaluria; Kidney Calculi; Male; Milk; Oxalates

Topics: Ascorbic Acid; Humans; Hyperoxaluria; Kidney; Kidney Transplantation; Oxalates

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

COVID-19 infection in kidney transplant recipients often lead to allograft dysfunction. The allograft injury has various histopathological manifestations. Our case illustrates the unusual combination of allograft rejection, acute kidney injury secondary to oxalate nephropathy and SARS CoV-2 nephropathy as the cause of irreversible allograft failure.. A 56 year old renal allograft recipient presented with a history of fever and diarrhoea for the preceding 4 weeks, tested positive for Sars-CoV2 on nasal swab and was found to have severe allograft dysfunction, necessitating haemodialysis. He subsequently underwent an allograft biopsy, which demonstrated antibody mediated rejection along with the presence of extensive oxalate deposition in the tubules. Ultrastructural examination demonstrated spherical spiked particles in the glomerular capillary endothelium and the presence of tubulo-reticular inclusions suggestive of an active COVID-19 infection within the kidney. The intra-tubular oxalate deposition was considered to be the result of high dose, supplemental Vitamin C used as an immune booster in many patients with COVID - 19 infection in India.. This case highlights the complex pathology that may be seen in following COVID-19 disease and the need for kidney biopsies in these patients to better understand the aetiology of disease.

Topics: Acute Kidney Injury; Ascorbic Acid; COVID-19; Fatal Outcome; Graft Rejection; Humans; Hyperoxaluria; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Primary Graft Dysfunction

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: Ascorbic Acid; Critical Care; Humans; Hyperoxaluria; Intensive Care Units; Oxalates

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

Hyperoxaluria and oxidative stress are risk factors in calcium oxalate (CaOx) stone formation. Supplement with antioxidant could be effective in prevention of recurrent stone formation. The present study aims to evaluate the protective effects of vitamin E and vitamin C in hyperoxaluric rat. The experiment was performed in rats for 21 days. Rats were divided into 5 groups as follows: control (group 1, n=8), hyperoxaluric rats (group 2, n=8), hyperoxaluric rats with vitamin E supplement (group 3, n=7), hyperoxaluric rats with vitamin C supplement (group 4, n=7) and hyperoxaluric rats with vitamin E and C supplement (group 5, n=7). Hyperoxaluria was induced by feeding hydroxyl L-proline (HLP) 2% w/v dissolved in drinking water. Intraperitoneal 200 mg/kg of vitamin E was given in groups 3 and 5 on days 1, 6, 11 and 16, while 500 mg of vitamin C was injected intravenously in groups 4 and 5 on days 1 and 11. Renal functions and oxidative status were measured. The urinary oxalate excretion was increased in HLP supplement rats, while glomerular filtration rate, proximal water and sodium reabsorption were significantly lower in group 2 compared with a control (P<0.05). Giving antioxidants significantly lower urinary calcium oxalate crystals (P<0.05). Hyperoxaluric rats had higher plasma malondialdehyde (PMDA) and lower urinary total antioxidant status (UTAS), which were alleviated by vitamin E and/or vitamin C supplement. In conclusion, giving combination of vitamin E and vitamin C exerts a protective role against HLP-induced oxalate nephropathy.

Topics: Animals; Antioxidants; Ascorbic Acid; Body Weight; Citrates; Drinking; Drug Therapy, Combination; Eating; Electrolytes; Hemodynamics; Hyperoxaluria; Kidney; Kidney Calculi; Kidney Glomerulus; Male; Oxalates; Protective Agents; Rats; Rats, Sprague-Dawley; Vitamin E

Hyperoxaluria can result in oxalate nephropathy with intratubular calcium oxalate crystallization and acute tubular injury. Primary inherited enzymatic deficiency or secondary causes such as excessive dietary intake, enteric increased absorption, or high doses of vitamin C, which is metabolized to oxalate, may underlie hyperoxaluria and oxalate nephropathy. We report a case of acute kidney injury due to oxalate nephropathy in a patient using chelating therapy with oral ethylenediamine tetra acetic acid (EDTA), intravenous supplementation with vitamin C, and chronic diarrhea and discuss the potential kidney damage these factors can cause in particular settings. To our knowledge, this is the first report suggesting an association between oral EDTA and oxalate nephropathy.

Topics: Acute Kidney Injury; Aged; Ascorbic Acid; Calcium Chelating Agents; Calcium Oxalate; Diarrhea; Edetic Acid; Humans; Hyperoxaluria; Kidney Tubular Necrosis, Acute; Male; Renal Dialysis; Vitamins

Klotho protein is recognized as having a renoprotective effect and is used as a biomarker for kidney injury. We investigated the level of Klotho protein in hyperoxaluria-induced kidney injury and the effects of vitamin E (Vit E) and vitamin C (Vit C) supplementation. Hyperoxaluria was induced by feeding 2% (w/v) Hydroxy-L-proline (HLP) in the drinking water for 21 days. Rats were divided into 5 groups; control (Group 1, n=7), HLP treated rats that received nothing else (Group 2, n=7), Vit E (Group 3, n=6), Vit C (Group 4, n=6) and both Vit E and Vit C (Group 5, n=7). Vit E (200 mg/kg) was injected on days 1, 6, 11 and 16, while Vit C (500 mg/kg) was given intravenously on days 1 and 11. The Klotho protein levels and oxidative status were measured. The expression level of kidney Klotho protein expression was significantly reduced by HLP-treatment, while the mRNA expression was higher (P<0.05), the plasma and kidney malondialdehyde and kidney superoxide dismutase activities were increased, and the kidney reduced glutathione and urinary total antioxidant status were decreased (P<0.05). All of these changes were ameliorated by administration of Vit E, Vit C or especially the co-administration of both. In conclusion, HLP-induced hyperoxaluria reduced the kidney Klotho protein level, which could be restored by Vit E and/or Vit C.

Topics: Animals; Antioxidants; Ascorbic Acid; Glucuronidase; Glutathione; Hyperoxaluria; Kidney; Klotho Proteins; Male; Malondialdehyde; Models, Animal; Rats, Sprague-Dawley; RNA, Messenger; Superoxide Dismutase; Vitamin E

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

Oxalate nephropathy is a rare condition characterized by extensive calcium oxalate deposition in the renal tubules, resulting in kidney injury. There are primary forms of the disease that arise from genetic mutation causing overproduction of oxalate. More commonly, this condition is seen as a secondary phenomenon. The clinical presentation is nonspecific, with acute kidney injury and normal serologic study results. The characteristic finding on kidney biopsy is the presence of acute tubular injury associated with polarizable crystals in the tubular lumen and epithelial cytoplasm. We present a case of acute oxalate nephropathy in a patient with underlying systemic lupus erythematosus who recently received intravenous vitamin C.

Topics: Acute Kidney Injury; Administration, Intravenous; Ascorbic Acid; Complementary Therapies; Female; Humans; Hyperoxaluria; Lupus Erythematosus, Systemic; Middle Aged; Vitamins

A 53-year-old contact lens wearer on renal dialysis developed visual impairment due to corneal opacity. The opacity was of a crystalline type and diffusely scattered in the anterior cornea. As oxalosis was suspected ascorbic acid was immediately omitted from the dialysis treatment schedule. Within a few weeks the visual acuity recovered and the corneas became nearly clear. The cornea is an uncommon manifestation site for oxalosis. Nevertheless, one should be aware of this possible sign for oxalosis, which can be a life-threatening complication of treatment with high dose ascorbic acid.

Topics: Adult; Ascorbic Acid; Corneal Opacity; Humans; Hyperoxaluria; Male; Renal Dialysis; Renal Insufficiency; Treatment Outcome; Vision Disorders

Topics: Anemia; Ascorbic Acid; Calcium Oxalate; Dose-Response Relationship, Drug; Drug Administration Routes; Humans; Hyperoxaluria; Iron Compounds; Renal Dialysis; Treatment Outcome; Uremia; Vitamins

In our efforts to meet the vitamin C requirements of dialysis patients we confront a medical dilemma--do we allow the patient to become depleted of vitamin C, with the accompanying hematological and other consequences (Scylla), or do we provide for adequate tissue levels of vitamin C, which has been thought to carry the risk of oxalosis (Charybdis). Many practitioners are certain that either one outcome (deficiency) or the other (oxalic acid toxicity) is inevitable, and much like Odysseus, no safe course is to be found. The recent accumulating evidence that vitamin C improves the management of anemia in dialysis patients compels us to find a safe passage through this dilemma. The serious vitamin C deficiency seen in many patients may also contribute to poor oral health and chronic fatigue. The evidence for oxalosis from vitamin C supplements stems from hemodialysis as practiced 20 years ago. Investigators using this therapy are not observing systemic oxalosis, and the most current data support the conclusion that vitamin C therapy is safe for dialysis patients. The question will be resolved by controlled trials that address both vitamin C effectiveness and safety.

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Erythropoiesis; Fatigue; Humans; Hyperoxaluria; Oral Health; Oxalates; Renal Dialysis

Topics: Administration, Oral; Ascorbic Acid; Calcium Oxalate; Dose-Response Relationship, Drug; Female; Humans; Hyperoxaluria; Kidney; Kidney Tubules, Proximal; Middle Aged

Increased rates of either oxalate absorption or endogenous oxalate synthesis can contribute to hyperoxaluria, a primary risk factor for the formation of calcium oxalate-containing kidney stones. This study involves a comparative assessment of oxalate absorption and endogenous oxalate synthesis in subpopulations of stone formers (SFs) and non-stone formers (NSFs) and an assessment of the effect of ascorbate supplementation on oxalate absorption and endogenous oxalate synthesis.. Twenty-nine individuals with a history of calcium oxalate kidney stones (19 men, 10 women) and 19 age-matched NSFs (8 men, 11 women) participated in two 6-day controlled feeding experimental periods: ascorbate-supplement (2 g/d) and no-supplement treatments. An oxalate load consisting of 118 mg of unlabeled oxalate and 18 mg of 13C2 -oxalic acid was administered the morning of day 6 of each experimental period.. Mean 13C2 -oxalic acid absorption averaged across the ascorbate and no-supplement treatments was significantly greater in SFs (9.9%) than NSFs (8.0%). SFs also had significantly greater 24-hour post-oxalate load urinary total oxalate and endogenous oxalate levels with both treatments. Twenty-four-hour urinary total oxalate level correlated strongly with both 13C2 -oxalic acid absorption (SFs, r = 0.76; P < 0.01; NSFs, r = 0.62; P < 0.01) and endogenous oxalate synthesis (SFs, r = 0.95; P < 0.01; NSFs, r = 0.92; P < 0.01).. SFs are characterized by greater rates of both oxalate absorption and endogenous oxalate synthesis, and both these factors contribute to the hyperoxaluric state. The finding that ascorbate supplementation increased urinary total and endogenous oxalate levels suggested that this practice is a risk factor for individuals predisposed to kidney stones.

Topics: Adult; Aged; Ascorbic Acid; Calcium Oxalate; Female; Humans; Hyperoxaluria; Kidney; Kidney Calculi; Male; Middle Aged; Oxalates

Renal injury is considered as one of the prerequisites for calcium oxalate retention. In order to determine the role of lipid peroxidation related effects for hyperoxaluria, we evaluated the alterations in lipid peroxidation, antioxidants and oxalate synthesizing enzymes in lithogenic rats with response to vitamin E + selenium treatment. In kidney of lithogenic rats, the level of lipid peroxidation and the activities of oxalate synthesizing enzymes were found to be increased whereas the levels/activities of non-enzymatic and enzymatic antioxidants were found to be decreased. The urinary excretion of both oxalate and calcium were significantly elevated. Supplementation of lithogenic rats with vitamin E + selenium decreased the levels of lipid peroxides and the activities of oxalate synthesizing enzymes like glycolic acid oxidase (GAO), lactate dehydrogenase (LDH), xanthine oxidase (XO) with a concomitant increase in the activities of enzymatic antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) and increased levels of non-enzymatic antioxidants like ascorbic acid, alpha-tocopherol and reduced glutathione (GSH). The urinary excretion of oxalate and calcium were normalized. The antioxidants vitamin E + selenium thereby protected from hyperoxaluria.

Topics: Alcohol Oxidoreductases; Animals; Antioxidants; Ascorbic Acid; Calcium Oxalate; Catalase; Dietary Supplements; Glucosephosphate Dehydrogenase; Glutathione; Glutathione Peroxidase; Hyperoxaluria; Kidney; L-Lactate Dehydrogenase; Lipid Peroxidation; Liver; Male; Rats; Rats, Wistar; Selenium; Superoxide Dismutase; Urinary Calculi; Vitamin E; Xanthine Oxidase

Lipoic acid (LA) and eicosapentaenoic acid (EPA) have been shown to ameliorate the changes associated with hyperoxaluria. This prompted us to study the effect of EPA-LA, a new derivative, in experimental urolithiatic condition. Foreign body implantation method followed by supplementation of ammonium oxalate was adopted to induce stone formation in the bladder. Significant depletion in the antioxidant status was observed in the kidney and bladder of stone-forming animals, associated with increased lipid peroxidation. The present observations provide supporting evidence to the hypothesis that free radicals might be involved in causing toxicity in hyperoxaluric condition. The three drugs, namely LA, EPA and EPA-LA had reversed the above changes, but the effect was more pronounced in EPA-LA-treated stone formers. These features highlight the beneficial effect of EPA-LA wherein the potency of two drugs has been combined. The practical outcome of these findings is that the cellular antioxidant defence can be increased by the supplementation of lipoate and its derivative EPA-LA.

Topics: Animals; Ascorbic Acid; Catalase; Eicosapentaenoic Acid; Free Radicals; Glutathione; Glutathione Peroxidase; Hyperoxaluria; Kidney; Male; Rats; Rats, Wistar; Superoxide Dismutase; Thioctic Acid; Urinary Bladder; Vitamin E

This study aimed to evaluate whether administration of cyclosporin to hyperoxaluric rats affects liver antioxidant status, and whether pretreatment with vitamin E reverses the effect. Male Wistar rats were divided into two major groups of 40. One group was given vitamin E. Both major groups were then divided into four subgroups which received vehicle (olive oil), cyclosporin in olive oil (50 mg kg(-1)), 3% ammonium oxalate or cyclosporin + 3% ammonium oxalate for three days. The activities of liver lactate dehydrogenase, glycolic acid oxidase and xanthine oxidase, and the level of malondialdehyde, an indicator of lipid peroxidation, increased when cyclosporin was administered to hyperoxaluric rats. The levels of antioxidants ascorbic acid, vitamin E and reduced glutathione and the activities of glutathione-metabolizing enzymes were altered significantly when hyperoxaluric rats were treated with cyclosporin. All these enzymes and antioxidants showed highly significant correlation values, r. These changes were restored to near normal by pretreatment with vitamin E. These findings suggest that cyclosporin-induced hepatotoxicity is aggravated in hyperoxaluria. This was almost totally prevented by pretreatment with vitamin E.

Topics: Animals; Antioxidants; Ascorbic Acid; Cyclosporine; Drug Interactions; Hyperoxaluria; Immunosuppressive Agents; Lipid Peroxidation; Liver; Liver Function Tests; Male; Oxalates; Rats; Rats, Wistar; Vitamin E

Long-term or high-dosage consumption of vitamin C may play a role in calcium oxalate kidney stone formation. The present study was undertaken to determine the biochemical and physicochemical risk factors in a male subject who developed haematuria and calcium oxalate crystalluria after ingestion of large doses of ascorbic acid for 8 consecutive days.. Twenty-four-hour urine samples were collected before and during the ascorbic acid ingestion period as well as after the detection of haematuria. A special procedure was implemented for urine collections to allow for oxalate, ascorbate and other urinalysis. Oxalate was determined in the presence of EDTA to prevent in vitro conversion to ascorbic acid, whereas ascorbate itself was determined by manual titration in a redox method using the dye dichlorophenolindophenol. Urinalysis data were used to compute calcium oxalate relative supersaturations and Tiselius risk indices, whereas scanning electron microscopy was used to examine urinary deposits.. Oxalate excretion increased by about 350% during ascorbate ingestion before haematuria. Ascorbate concentrations also increased dramatically but appeared to reach a plateau maximum. Increasing calcium excretion was accompanied by decreasing potassium and phosphate values. The calcium oxalate relative supersaturation and Tiselius risk index increased during vitamin C ingestion and large aggregates of calcium oxalate dihydrate crystals were observed by scanning electron microscopy immediately after the detection of haematuria.. High percentage metabolic conversion of ascorbate to oxalate in this subject caused relative hyperoxaluria and crystalluria, the latter manifesting itself as haematuria. Clinicians need to be alerted to the potential dangers of large dose ingestion of vitamin C in some individuals.

Topics: Adult; Ascorbic Acid; Calcium Oxalate; Crystallization; Hematuria; Humans; Hyperoxaluria; Kidney Calculi; Male; Microscopy, Electron, Scanning; Risk Factors; Time Factors

The hyperoxaluric rat kidney nucleus exhibited a 50% increase in oxalate binding activity of control in both the residual fraction containing nuclear envelopes and the histone fraction with a concomitant increase in basal lipid peroxidation and a decrease in thiol content. However, in vitro lipid peroxidation induced by the ascorbate-ADP-Fe3+ system increased the oxalate binding activity of the residual fraction with a positive correlation but inhibited the histone oxalate binding activity with a negative correlation with depletion of thiols during peroxidation in both control and hyperoxaluric rats. A twofold increase in oxalate concentration was observed in the nucleus as well as the nuclear subfractions in hyperoxaluria. Hyperoxaluric rat kidneys showed increased H1 and oxalate binding activity, and the distribution of H1B was higher than that in the control. The present study suggests that the increased nuclear oxalate binding activity in hyperoxaluric rats was not due to lipid peroxidation but due to increased formation of histone H1.

Topics: Animals; Ascorbic Acid; Cell Nucleus; Histones; Hyperoxaluria; Kidney; Kidney Tubules; Lipid Peroxidation; Male; Oxalates; Rats; Rats, Wistar

Oxalosis, or calcium oxalate deposition in the tissues, may develop in patients with inherited disorders of oxalate metabolism or can occur secondary to other diseases. In this study, a case of renal oxalosis probably secondary to excessive parenteral vitamin C administration in a patient with acute post-traumatic oliguric renal failure is reported. Oxalate deposits may have contributed to further worsening and delayed recovery of renal function. The elimination of the source of excess vitamin C and its presumed effect on oxalate production, together with enhanced removal of oxalate during aggressive dialysis, resulted in prompt recovery of renal function. Secondary oxalosis represents a possible cause of delayed recovery of renal function in patients with acute renal failure who are receiving vitamin C supplementation if excess dosage of that supplementation is given. Vitamin C supplementation, if utilized, should be carefully monitored in patients receiving artificial renal replacement therapy.

Topics: Ascorbic Acid; Biopsy; Calcium Oxalate; Dose-Response Relationship, Drug; Fatal Outcome; Humans; Hyperoxaluria; Infusions, Intravenous; Kidney; Kidney Function Tests; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Renal Dialysis

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

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

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