Long-term clinical outcome for patients poisoned by the fungal nephrotoxin orellanine

Abstract

BackgroundAccidental 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.MethodsWe 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.ResultsThe 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.ConclusionWe 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.

Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats

“…Although research so far has explored the effects of orellanine toxicity and effects on kidney function [ 13 , 21 ], there is a need for a better understanding of the pharmacokinetic properties of this nephrotoxin. This might help in understanding future deadly webcap poisoning cases in improving clinical management [ 18 ] as well as opening the way for orellanine as a potential cure for metastatic end stage renal carcinoma [ 8 ]. New and curative therapy options for this type of cancer is needed since the outcome for patients with metastatic disease still is poor even though several therapeutic options have been suggested [ 22 , 23 , 24 , 25 ].…”

“…Other organs displayed higher levels of 3 H than the blood after 24 h except for the kidney cortex and urine, the liver, spleen, and bone marrow even though these levels were much lower than for the kidney and urinary system. There are no reports of patients with orellanine intoxication having any damage to any other organs except the kidneys [ 18 ].…”

“…In a retrospective case control study, orellanine-intoxicated patients where compared to patients with renal failure due to other causes. No differences between the groups were seen in damage to other organs or in cause of death [ 18 ]. It is known that orellanine is excreted from the body into the urine during the first 24 h after intake [ 17 ] and that plasma levels are undetectable a few days after intoxication [ 19 ].…”

Orellanine specifically targets renal clear cell carcinoma

“…In a small retrospective study 28 patients who accidentially ingested the deadly webcaps were compared to matched dialysis or transplant controls. We saw that both groups had similar life expectancy and died of similar causes [ 18 ]. This report further strengthens the findings in this paper, that the toxicity of orellanine specifically targets proximal tubular cells and cancer cells of the same origin.…”

Distribution of edible, toxic and medicinal wild mushrooms in Europe and Bulgaria

“…The species Cortinarius orellanus of the Cortinarius genus is typically found in Europe and this mushroom has caused a mass poisoning in Poland in the 1950s [30]. The Cortinarius 'deadly webcap' mushroom species identified in forests of Northern Europe and Scandinavia may be mistaken for other edible mushrooms [31].…”