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Background: Accidental intake of mushrooms of the Cortinarius species (deadly webcap) may cause irreversible renal damage and the need for dialysis or transplantation. The species is found in forests of Northern Europe, Scandinavia and North America and may be mistaken for other edible mushrooms. The highly selective nephrotoxic compound of the mushroom is called orellanine. Very little is known about the long-term effects of the nephrotoxin., Methods: We identified patients who ingested deadly webcap in the period of 1979 to 2012. Informed consent and medical records were obtained for 28 of the 39 cases that occurred during the 34-year period. A case control group was also studied based on sex, age and initiation of dialysis or transplantation., Results: The average age at time of the accidental intake was 40 ± 3 (n = 28) years. 64% of patients were male, and 22 of 28 patients developed acute kidney injury requiring dialysis. Serum creatinine peaked at 1 329 ± 133 μmol/l, and serum urea was 31 ± 3.5 mmol/l. No signs of acute damage were present in any other organ. The average time of follow-up was 16.9 ± 2.1 years (1.24-34.3 years, n = 28). 15 patients were transplanted and 3 also had a second graft. At follow-up, 23 patients were alive, and five had died at ages of 67 ± 5 (range 54-84). The outcome was similar in the case control group with 6 deaths in 20 patients., Conclusion: We conclude that the long-term prognosis for patients poisoned by deadly webcap who lost their renal function is not different compared to other patients in active uremic care.

Orellanine (3,3',4,4'-tetrahydroxy-2,2'-bipyridine-1,1'-dioxide) is a tetrahydroxylated di-N-oxidized bipyridine compound. The toxin, present in certain species of Cortinarius mushrooms, is structurally similar to herbicides Paraquat and Diquat. Cortinarius orellanus and Cortinarius rubellus are the major orellanine-containing mushrooms. Cortinarius mushrooms are widely reported in Europe where they have caused human poisoning and deaths through accidental ingestion of the poisonous species mistaken for the edible ones. In North America, Cortinarius orellanosus mushroom poisoning was recently reported to cause renal failure in a Michigan patient. Cortinarius mushroom poisoning is characterized by delayed acute renal failure, with some cases progressing to end-stage kidney disease. There is debate whether other Cortinarius mushroom contain orellanine or not, especially in North America. Currently, there are no veterinary diagnostic laboratories in North America with established test methods for detection and quantitation of orellanine. We have developed two diagnostic test methods based on HPLC and LC-MSMS for identification and quantitation of orellanine in mushrooms. Using these methods, we have identified Cortinarius armillatus as a novel orellanine-containing mushroom in North America. The mean toxin concentration of 145 ug/g was <1% of that of the more toxic C. rubellus. The HPLC method can detect orellanine at 17 μg g(-1) while the LC-MSMS method is almost 2000 times more sensitive and can detect orellanine at 30 ng g(-1). Both tests are quantitative, selective and are now available for veterinary diagnostic applications., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

History and Clinical Findings: A 26-year-old woman with no contributory medical history became anuric after several days of nausea and vomiting. She was admitted to our hospital with suspected acute renal failure., Investigations: Laboratory tests revealed greatly elevated BUN and creatinine. There was no evidence of postrenal obstruction, infection or systemic disease. Kidney biopsy showed interstitial nephritis., Diagnosis, Therapy and Clinical Course: Further questioning revealed poisoning with a nephrotoxic mushroom of the genus Cortinarius, which the patient had eaten together with her husband nine days before admission. The patient's husband developed anuric renal failure, too, and was admitted to our hospital. Hemodialysis was instituted on day 1. More than one year later, both patients remain on chronic dialysis., Conclusions: Intoxication with mushrooms of the genus Cortinarius should be considered in the differential diagnosis of otherwise unexplained acute renal failure, especially in autumn and late summer. These mushrooms can cause an interstitial nephritis. Once dialysis has to be instituted the prognosis is rather poor: 50 % of these patients develop chronic renal failure. So far there is no causative therapy. In case of chronic renal failure, kidney transplantation is possible.

Mushrooms are ubiquitous in nature. They are an important source of nutrition, however, certain varieties contain chemicals that can be highly toxic to humans. Industrially cultivated mushrooms are historically very safe, whereas foraging for mushrooms or accidental ingestion of mushrooms in the environment can result in serious illness and death. The emergency department is the most common site of presentation for patients suffering from acute mushroom poisoning. Although recognition can be facilitated by identification of a characteristic toxidrome, the presenting manifestations can be variable and have considerable overlap with more common and generally benign clinical syndromes. The goal of this two-part article is to review the knowledge base on this subject and provide information that will assist the clinician in the early consideration, diagnosis and treatment of mushroom poisoning. Part I reviewed the epidemiology and demographics of mushroom poisoning, the physical characteristics of the most toxic varieties, the classification of the toxic species, and presented an overview of the cyclopeptide-containing mushroom class. Part II is focused on the presentation of the other classes of toxic mushrooms along with an up-to-date review of the most recently identified poisonous varieties.

We describe three cases of acute renal failure in young men who ingested wild mushrooms with the intent of producing hallucinations. Two cases remained dialysis dependent and, in these cases, renal biopsy revealed tubulointerstitial nephritis and fibrosis. Similar cases have been reported in other countries, but not in Australia. The most recognized mushroom nephrotoxin is orellanine, however the causative mushroom species and the actual toxin involved in these cases are unknown.

In August 1995 a 23-year-old man was admitted to the hospital because of acute anuria. 14 days prior to admission he had consumed five fruit bodies of raw mushrooms of the Cortinarius speciocissimus species. The tentative diagnosis of acute renal failure due to orellanine intoxication was confirmed by the histologic finding of an acute interstitial nephritis in a first renal biopsy one week after onset of anuria. The patient required hemodialysis for the following weeks and months, is now on peritoneal dialysis and is awaiting renal transplantation. Six months after onset of symptoms a second renal biopsy was performed, which revealed increasing interstitial fibrosis. In contrast to the findings of Rapior et al. 1989, orellanine could not be detected in this specimen. The negative toxin test in this second renal biopsy is possibly explained by a wide variability of pharmacokinetics of orellanine.

Orellanine, (2,2'-bipyridine)-3,3',4,4'-tetrol-1,1'-dioxide, the toxin from several Cortinariace species, induces an acute renal failure which can be very severe or even irreversible and fatal. It is therefore important to be able to quickly and simply identify orellanine in mushroom samples with classical methods, readily available in any laboratory, such as anti-poison centers. This article reports the results of three analytical methods: classical TLC on cellulose plates in n-butanol--acetic acid--water and two original methods, electrophoresis on agarose gel and direct electron spin resonance (ESR) after enzymatic oxidation. They were applied to detect orellanine in 34 Cortinariaceae and 4 other species of toadstools. Our three sets of results are convergent. TLC (detection limit: 15 ng with fluorescence densitometry), electrophoresis (25 ng) and even ESR (5 micrograms), are sensitive enough for our purpose, and a sophisticated method like HPLC (detection limit: 50 pg) is not required. As the ESR spectrum of the toxin semiquinone is highly specific, TLC or electrophoresis coupled with ESR are a convenient alternative to liquid chromatography coupled with mass spectrometry, with the same specificity, for a confirmation or with samples such as ours with high toxin contents. ESR unambiguously confirms the relatively high contents of orellanine, from 0.45% (C. henrici) to 1.1-1.4% (C. orellanus), found in five Cortinarius from the subgenus Leprocybe, section Orellani. The five species, though they are from different geographic origins, have a more or less common pattern of fluorescent compounds, among which orellinine and orelline beside orellanine. It can be useful to note that orellanine semiquinone can be easily detected by ESR directly in the fresh mushroom. The toxin is absent in the other mushrooms we tested, especially in D. cinnamomea and C. splendens, which have been claimed as toxic and suspected to contain orellanine.

Pesticide constitute a large group of commonly used chemicals with diverse chemical structure and toxicity. They are intended mostly to protect plants and plant products from the activity of various harmful organisms but they can also be used as biocides. Pesticide poisonings may be due to suicidal attempts or accidental ingestion associated with improper storage in unlabelled containers. Severe cases are treated at the regional poison units while others in the in-patient and out-patient clinics all over the country. The study made us draw the conclusion that poisonings with organophosphates and dipyridyl derivatives pose an essential toxicological problem. They are usually severe and require long hospitalisation. The highest morality rate was noted also for the poisonings with organophosphates and dipyridyl derivatives. Suicidal attempts constitute the most frequent cause of the poisonings. The results of the analysis imply a necessity to replace the most harmful organophosphate and dipyridyl pesticides with others of a lower toxicity class. It should be underlined that in order to avoid an accidental misuse, pesticides should be stored in the original, labelled containers.

Background: Mushroom poisoning by some species of the Cortinarius (Agaricales) often lead to irreversible renal failure caused by the nephrotoxin orellanine. In 1994 and 1995, six poisoning outbreaks involving ten individuals in Northern Italy and in Austria were investigated., Methods: A total of 87 clinical samples (urine and blood samples including renal biopsy material of three patients) were examined for the presence of orellanine by thin layer chromatography., Results: Orellanine can be detected after a relatively long period following poisoning by performing a simple thin layer chromatography technique using small quantities of renal biopsy material. No toxin was found in urine or blood samples., Conclusions: Orellanine is rapidly concentrated in the kidneys in a relatively soluble form and cannot be detected in urine, blood and dialysis fluids at the time when first symptoms appear.

Orellanin poisoning is characterized by an acute renal failure which can be lethal if the appropriate treatment is not given. A 31-year old woman was admitted to hospital 10 days after she had deliberately ingested 2 raw carpophores of the mushroom Cortinarius orellanus. Acute renal failure (creatininaemia 1,100 mumol/l) developed, requiring 6 sessions of haemodialysis, one of plasmapheresis and the administration of diltiazem and aminoacids. Plasma and tissue assays of orellanin, the mushroom's toxin, were performed by two-dimensional thin layer chromatography. Before haemodialysis and 10 days after ingestion of the poison, the plasma contained orellanin. Eighteen months after the attempted suicide, the plasma creatinine level was 181 mumol/l.

Symptomatology, clinical characteristics and pathogenesis of mushroom poisoning caused by Cortinarius species are surveyed. The isolation of a bipyridine--orellanine--from Cortinarius orellanus is held to be responsible for the nephrotoxicity of this species as well as the closely related C. speciosissimus. The present knowledge on the toxicity of structurally related and well-known bipyridines such as paraquat and diquat is brought up and found comparable to orellanine toxicity. Pharmacokinetic experiments on the nephrotoxic bipyridines suggest that haemoperfusion is a rational therapy of intoxicated persons, even several days after mushroom ingestion.

From the clinico-toxicological standpoint, the most important plant protectants are the insecticides (bipyridylium compounds). In vitro trials and investigations on poisoned patients have shown that it is fundamentally possible to eliminate such plant protectants from the blood by hemoperfusion with coated activated charcoal. With both the lipophilic alkyl phosphate, nitrostigmine (E605 forte), and by the two hydrophilic alkyl phosphates, demetone-S-methyl sulfoxide (Metasystox R) and dimethoate (Roxion), it was possible to measure hemoperfusion clearance values around 60 to 85 ml/min at a blood flow rate of 100 ml/min. Only the two hydrophilic alkyl phosphates were able to be eliminated by hemodialysis, the clearance values being, however, lower. Thus in severe alkyl phosphate intoxications the use of hemoperfusion may considered alongside the standard therapy. The bipyridylium compounds, paraquat (Gramoxone) and diquat (Reglone), are readily dialysed, but can be better eliminated from the blood by hemoperfusion. This therapeutic measure must be initiated as rapidly as possible independent of the clinical picture, for only when hemoperfusion is begun prior to the fixation of paraquat or diquat at tissue are there any prospects of success.

A woman suffering from acute tubulo-interstitial nephritis was admitted to the hospital ten days after deliberate intoxication by ingestion of Cortinarius orellanus. Orellanine, the main toxin responsible for orellanine poisoning, was detected in biological fluids and renal biopsies. It was assayed by direct spectrofluorimetry on two-dimensional thin-layer chromatograms after specific photodecomposition into orelline. The orellanine concentration was 6.12 mg/l in the plasma (10 days after ingestion). Orellanine levels in renal biopsies were 7 micrograms per 25 mm3 of the first biopsy (13 days after ingestion) and 24 micrograms per 8 mm3 of the second biopsy (6 months later).