Development of End Stage Renal Disease after Long-Term Ingestion of Chaga Mushroom: Case Report and Review of Literature.

Chaga mushrooms are widely used in folk remedies and in alternative medicine. Contrary to many beneficial effects, its adverse effect is rarely reported. We here report a case of end-stage renal disease after long-term taking Chaga mushroom. A 49-year-old Korean man with end stage renal disease (ESRD) was transferred to our hospital. Review of kidney biopsy finding was consistent with chronic tubulointerstitial nephritis with oxalate crystal deposits and drug history revealed long-term exposure to Chaga mushroom powder due to intractable atopic dermatitis. We suspected the association between Chaga mushroom and oxalate nephropathy, and measured the oxalate content of remained Chaga mushroom. The Chaga mushroom had extremely high oxalate content (14.2/100 g). Estimated daily oxalate intake of our case was 2 times for four years and 5 times for one year higher than that of usual diet. Chaga mushroom is a potential risk factor of chronic kidney disease considering high oxalate content. Nephrologist should consider oxalate nephropathy in ESRD patients exposed to Chaga mushrooms.

Oxalate nephropathy following vitamin C intake within intensive care unit
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OBJECTIVE: To report a case of acute oxalate nephropathy related to vitamin C intake within the intensive care unit (ICU). DESIGN: Case report. SETTING: ICU and nephrology department of a French university hospital. PATIENT: A 57-year-old woman with septic shock related to Legionella pneumophila pneumonia complicated by acute respiratory distress syndrome and acute kidney injury who required renal replacement therapy for 75 days. MEASUREMENTS AND MAIN RESULTS: A renal biopsy was performed on day 72 because of persistent anuria and because the patient showed characteristic features of severe acute oxalate nephropathy. The only cause identified was vitamin C intake received during hospitalization within the ICU (~ 30 g over 2.5 months). At month 6 after ICU admission, estimated glomerular filtration rate was 24 mL/min/1.73m2. CONCLUSION: Compelling evidence obtained from in-vitro and animal studies suggest that vitamin C, a circulating antioxidant, may be a valuable adjunctive therapy in critically-ill patients. Data from humans are more conflicting. Oxalate, a well-known metabolite of vitamin C, is excreted by the kidneys and can exert a toxic effect on epithelial cells and causes direct tubular damage, and/or it can crystallize within the tubular lumen. This case highlights an under-recognized secondary adverse event from vitamin C given to critically-ill patients. The use of high-dose vitamin C should be prescribed with caution in this population.
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Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in Chronic Kidney Disease.

In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of death. Some uremic toxins are ingested with the diet, such as phosphate and star fruit-derived caramboxin. Others result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves. These nutrients include l-carnitine, choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over-the-counter as nutritional supplements. Physicians and patients alike should be aware that, in CKD patients, the use of these supplements may lead to potentially toxic effects. Unfortunately, most patients with CKD are not aware of their condition. Some of the dietary components may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins, such as trimethylamine N-Oxide (TMAO), p-cresyl sulfate, indoxyl sulfate and indole-3 acetic acid. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of death and cardiovascular disease and there is evidence that this association may be causal. Future developments may include maneuvers to modify gut processing or absorption of these nutrients or derivatives to improve CKD patient outcomes.

Preventive treatment of calcium oxalate crystal deposition with immortal flowers.

ETHNOPHARMACOLOGICAL RELEVANCE: A number of medicinal plants are used for their diuretic, urolithiatic and anti-inflammatory effects on urinary system problems in Turkey and the most common traditional remedy for kidney stones is the tea of immortal flowers. The aim of this study is to evaluate the preventive effect of infusions prepared from capitulums of Helichrysum graveolens (M.Bieb.) Sweet (HG) and Helichrysum stoechas ssp. barellieri (Ten.) Nyman (HS) on formation of kidney stones. MATERIALS AND METHOD: Sodium oxalate (Ox-70mg/kg intraperitoneally) was used to induce kidney stones on Wistar albino rats. At the same time, two different doses of the plant extracts (HG: 62.5 and 125mg/kg; HS: 78 and 156mg/kg) were dissolved in the drinking water and administered to animals for 5 days. Potassium citrate was used as positive control in the experiments. During the experiment, water intake, urine volume and body weights of the animals were recorded. At the end of the experiments, liver, kidney and body weights of the animals were determined; biochemical analysis were conducted on urine, blood and plasma samples. Histopathological changes in kidney tissues were examined and statistical analysis were evaluated. RESULTS: HS extract showed the highest preventive effect at 156mg/kg dose (stone formation score: 1.16), whereas a number of kidney stones were maximum in sodium oxalate group (stone formation score: 2.66). Helichrysum extracts decreased urine oxalate and uric acid levels and increased citrate levels significantly. In addition, Helichrysum extracts regulated the negative changes in biochemical and hematological parameters occurred after Ox injection. CONCLUSIONS: We conclude that Helichrysum extracts could reduce the formation and growth of kidney stones in Ox-induced urolithiasis and can be beneficial for patients with recurrent stones. In addition, this is the first study on the preventive effect of immortal flowers.

Effects of the selective sigma receptor ligand, 1-(2-phenethyl)piperidine oxalate (AC927), on the behavioral and toxic effects of cocaine.

BACKGROUND: Sigma receptors represent a unique structural class of proteins and they have become increasingly studied as viable medication development targets for neurological and psychiatric disorders, including drug abuse. Earlier studies have shown that cocaine and many other abused substances interact with sigma receptors and that antagonism of these proteins can mitigate their actions. METHODS: In the present study, AC927 (1-(2-phenethyl)piperidine oxalate), a selective sigma receptor ligand, was tested against the behavioral and toxic effects of cocaine in laboratory animals. RESULTS: Acute administration of AC927 in male, Swiss Webster mice significantly attenuated cocaine-induced convulsions, lethality, and locomotor activity, at doses that alone had no significant effects on behavior. Subchronic administration of AC927 also attenuated cocaine-induced conditioned place preference in mice, at doses that alone had no effects on place conditioning. In drug discrimination studies in male, Sprague-Dawley rats, AC927 partially substituted for the discriminative stimulus effects of cocaine. When it was administered with cocaine, AC927 shifted the cocaine dose-response curve to the left, suggesting an enhancement of the discriminative stimulus effects of cocaine. In non-human primates, AC927 was self-administered, maintaining responding that was intermediate between contingent saline and a maintenance dose of cocaine. CONCLUSION: The ability of AC927 to elicit some cocaine-like appetitive properties and to also reduce many cocaine-induced behaviors suggests that it is a promising lead for the development of a medication to treat cocaine abuse.

Effects of green tea on urinary stone formation: an in vivo and in vitro study.

PURPOSE: We evaluated whether epigallocatechin gallate (EGCG), a main constituent of green tea polyphenols, could protect against cellular toxicity by oxalate and whether green tea supplementation attenuates the development of nephrolithiasis in an animal model. MATERIALS AND METHODS: Cells of the NRK-52E line were incubated with different concentrations of oxalate with and without EGCG, and toxicity and malondialdehyde assays were done to investigate the cytotoxic effect of oxalate and the anti-oxalate effect of EGCG.. In a second series of experiments, male Sprague-Dawley rats were divided into three groups. Group 1 animals (controls) were fed regular chow and drank water ad libitum; group 2 animals were fed chow containing 3% sodium oxalate with the administration of gentamicin (40 mg/kg) and drank water ad libitum; group 3 animals were fed the same diet as group 2 with gentamicin administration and drank only green tea. Rats were killed 4 weeks later after a 24-hour urine collection, and the kidneys were removed for morphologic examination. RESULTS: As oxalate concentrations increased, the number of surviving cells decreased, and the formation of free radicals increased. The administration of EGCG inhibited free-radical production induced by oxalate. Green tea supplementation decreased the excretion of urinary oxalate and the activities of urinary gammaglutamyltranspeptidase and N-acetylglucosaminidase. The number of crystals within kidneys in group 3 was significantly lower than in group 2. CONCLUSIONS: Green tea has an inhibitory effect on urinary stone formation, and the antioxidative action of EGCG is considered to be involved.

Mode of action: oxalate crystal-induced renal tubule degeneration and glycolic acid-induced dysmorphogenesis--renal and developmental effects of ethylene glycol.

Ethylene glycol can cause both renal and developmental toxicity, with metabolism playing a key role in the mode of action (MOA) for each form of toxicity. Renal toxicity is ascribed to the terminal metabolite oxalic acid, which precipitates in the kidney in the form of calcium oxalate crystals and is believed to cause physical damage to the renal tubules. The human relevance of the renal toxicity of ethylene glycol is indicated by the similarity between animals and humans of metabolic pathways, the observation of renal oxalate crystals in toxicity studies in experimental animals and human poisonings, and cases of human kidney and bladder stones related to dietary oxalates and oxalate precursors. High-dose gavage exposures to ethylene glycol also cause axial skeletal defects in rodents (but not rabbits), with the intermediary metabolite, glycolic acid, identified as the causative agent. However, the mechanism by which glycolic acid perturbs development has not been investigated sufficiently to develop a plausible hypothesis of mode of action, nor have any cases of ethylene glycol-induced developmental effects been reported in humans. Given this, and the variations in sensitivity between animal species in response, the relevance to humans of ethylene glycol-induced developmental toxicity in animals is unknown at this time.

Genotoxicity of trivalent chromium in bacterial cells. Possible effects on DNA topology.

Trivalent chromium is a metal required for proper sugar and fat metabolism. However, it has been suggested that it causes DNA damage in in vitro test systems, although in vivo toxicity has not yet been proved. In the present study, the effect of Cr3+ on bacterial cells was tested with the Pro-Tox (C) assay, and its cellular uptake was measured with flame atomic absorption spectroscopy. The potential genotoxicity of Cr3+ was further examined by the study of its influence on a bacterial type II topoisomerase. Cr3+ was shown to cause DNA damage and inhibit topoisomerase DNA relaxation activity, probably by preventing the formation of the covalent link between enzyme and double helix. In addition, Cr3+ decreases the viability and/or proliferation rate of eukaryotic cells such as murine B16 melanoma cells and human MCF-10A neoT ras-transformed human epithelial cells. The possible implication for Cr3+ intake by humans is discussed.

Effects of oxalate on HK-2 cells, a line of proximal tubular epithelial cells from normal human kidney.

PURPOSE: Oxalate, a metabolic end product, is a major constituent of majority of renal stones. Previous studies with LLC-PK1 cells, a line of proximal renal epithelial cells of porcine origin, have shown that oxalate produces time and concentration dependent effects on the growth and viability of these cells. We assessed the possibility that oxalate may be toxic to HK-2 cells, a line of human proximal renal epithelial cells. MATERIALS AND METHODS: HK-2 cells were maintained in Dulbecco's modified Eagle's medium supplemented with fetal bovine serum and antibiotics. Cells were exposed to oxalate for various intervals. Trypan blue exclusion criteria were used to assess membrane integrity, cell morphology was assessed by hematoxylin and eosin staining and crystal violet staining was used to measure cell density. DNA synthesis was measured by [3H]-thymidine incorporation and superoxide production was measured by the nitroblue tetrazolium reduction method. RESULTS: Exposure of HK-2 cells to oxalate produced time and concentration dependent increase in the membrane permeability to trypan blue and changes in the light microscopic appearance of the cells. Long-term exposure to oxalate resulted in an increase in DNA synthesis and alterations in cell viability with net cell loss after exposure to high oxalate concentrations. CONCLUSIONS: To our knowledge the results provide the first direct demonstration of the toxic effects of oxalate in HK-2 cells, a line of human renal epithelial cells, and suggest that hyperoxaluria may contribute to renal tubular damage associated with calcium oxalate stone disease.

Vitamin E pretreatment prevents cyclosporin A-induced crystal deposition in hyperoxaluric rats.

The in vivo effect of cyclosporin A (CsA) on renal calcium oxalate (CaOx) crystal retention in experimental hyperoxaluric rats was investigated. Further, the effect of pretreatment of vitamin E on the above conditions was also studied. Male Wistar rats were divided into two major groups each containing 40 rats. One of the groups was pretreated with vitamin E. Both major groups were then subgrouped into four groups: group 1 received the vehicle (olive oil); group 2 received CsA in olive oil (50 mg/kg); group 3 received 3% ammonium oxalate (AmOx), and group 4 received CsA + AmOx. Nephrotoxicity was assessed by the activities of urinary marker enzymes and also by histopathology. Urinary oxalate excretion as well as the activities of lactate dehydrogenase, gamma-glutamyltranspeptidase, alkaline phosphatase and inorganic pyrophosphatase enzymes were elevated either in CsA-alone or AmOx-alone treated groups. On combined administration of both CsA and AmOx, further elevations of these enzymes were observed. Urinary excretion of oxalate concentration positively correlated with urinary excretion of these enzymes. Deposition of CaOx crystals was seen only in the kidneys of rats that received combined treatment. On pretreatment with vitamin E the observed increased urinary activities of the enzymes and oxalate, histopathological changes and the deposition of CaOx crystals by administration of CsA in hyperoxaluria were prevented suggesting that vitamin E could be supplemented to prevent CsA-induced membrane damage.

Acute inhalation toxicology of oxalyl chloride.

The acute inhalation LC50 of oxalyl chloride was determined in rats following a one-hour exposure. Four groups of 10 animals per group were exposed to a concentration range of 462-2233 ppm. One set of six animals was exposed to a concentration of oxalyl chloride of 1232 ppm for one hour to evaluate the histopathological change to the lungs. The LC50 is 1840 ppm with the 95% confidence interval between 1531 ppm and 2210 ppm. Microscopically, the lungs from the treated animals exhibited acute bronchiolitis, exudate within the alveoli, and congestion. Pulmonary edema appears to contribute significantly to mortality produced by oxalyl chloride. A comparison of the acute one-hour LC50 of oxalyl chloride to that of hydrogen chloride, phosgene, phosphorus oxychloride, boron trichloride, and chlorine indicates that it shares a comparable degree of acute toxicity to hydrogen chloride and is significantly less toxic via inhalation than the latter four chemicals.

Pharmacological study of the muscle paralyzing activity of the juice of the banana trunk.

Extracts of the juice of the banana trunk were assayed in the isolated phrenic nerve-diaphragm muscle preparation of the rat. The chemical composition of those producing muscular paralysis was then studied. As active extracts mainly consisted of monopotassium oxalate, the effect of this compound on the muscle preparation was investigated and compared with that of the active extracts. The pattern of muscular paralysis induced by monopotassium oxalate was the same as that seen with the juice extracts. Likewise inhibition of contractions of the tibialis muscle was observed in vivo after intra-arterial administration of both the crude concentration of the juice and monopotassium oxalate. These findings suggest that monopotassium oxalate could be responsible for the muscular paralysis caused by the juice of banana trunk.

Comparative toxicity of trivalent and hexavalent chromium compounds in fig moth Ephestia cautella (Walker).

Of the trivalent (CrSO4) and hexavalent (K2Cr2O7) chromium compounds, only the hexavalent produced significant deleterious effects on development and fertility of E. cautella, when eggs were reared on laboratory medium supplemented with different concentrations of these salts.