‘Shroom’ for concern: a case of psychedelic mushroom-induced acute kidney injury

Psilocybe cubensis mushrooms are typically not consumed for their nutritional value. The main reason people ingest these mushrooms is for their psychoactive effects. Recently, there has been growing interest in the potential therapeutic applications of psilocybin-containing mushrooms in a range of psychiatric conditions, including depression, anxiety disorders, obsessive-compulsive disorder, alcohol dependence and tobacco dependence. Here, we present a case in which ingestion of psilocybin-containing mushrooms was the presumed cause of acute kidney injury (AKI). A man in his early thirties presented with acute bilateral flank pain 48 h following recreational ingestion of 0.5 g of psilocybin-containing mushrooms in dry whole form. He experienced the desired and expected hallucinogenic effects upon initial consumption. He developed a non-oliguric AKI with a peak serum creatinine of 189 μmol/L, elevated from a known baseline of 83 μmol/L. Urinalysis demonstrated an elevated albumin-creatinine ratio (40.4 mg/mmol) and bland urinary sediment. Non-contrast computed tomography of the kidneys, ureter and bladder was unremarkable. A comprehensive work-up for glomerulonephritis was negative. Serum electrolytes remained within normal limits, and there was no peripheral eosinophilia. Liver function tests were unremarkable apart from a borderline elevation in aspartate aminotransferase at 39 U/L, and serum lipase was mildly elevated at 82 U/L. A creatine kinase was normal at 155 U/L. No alternative nephrotoxic exposures or contributing factors were identified on detailed clinical history. More specifically, he had no symptoms of vomiting or diarrhoea that may have contributed to a state of dehydration. Physical examination was unremarkable, with no costovertebral angle tenderness and evidence of clinical euvolaemia. The patient received supportive management with intravenous fluids, resulting in resolution of flank pain within 48 h. Serum creatinine improved to 136 μmol/L by day 4, so a kidney biopsy was not pursued. At 1 month follow-up, renal function had fully recovered, with his serum creatinine returning to 85 μmol/L. Psilocybin-containing mushrooms are primarily associated with transient neuropsychiatric effects - altered mood, perception and cognition - emerging within 20-40 min of ingestion and resolving within 6 h. While not traditionally associated with nephrotoxicity, it is hypothesised that their serotonergic activity, particularly via 5-HT2A receptor agonism, may lead to vasoconstriction and tubular injury.1 Several cases of nephrotoxicity linked to psilocybin ingestion have been reported.1-3 These exposures rely on correct preparation and sufficiently skilful identification of the product to ensure there are no contaminants which could contribute to the development of AKI. Nephrotoxicity secondary to mushroom ingestion is usually associated with the orellanine-containing Cortinarius species and the amatoxin-producing Amanita species. Orellanine nephrotoxicity is characterised by a delayed-onset AKI, typically manifesting 3-20 days after ingestion. Histopathology demonstrates tubular necrosis, interstitial oedema and fibrosis. These cases often progress to chronic kidney disease requiring dialysis and transplant.4 Amatoxins - most notably from Amanita phalloides, A. verna, and A. virosa - are classically hepatotoxic, but nephrotoxicity has been reported due to severe dehydration from profuse diarrhoea, direct tubular toxicity or secondary to hepatorenal syndrome.5 Histopathology typically reveals tubular necrosis and interstitial nephritis. Other Amanita species may cause an early-onset AKI, typically within 24-72 h, with more favourable prognosis and renal recovery.6 Mechanistically, orellanine is thought to inhibit protein synthesis and induce oxidative damage via free radical generation,7 while amatoxins inhibit RNA polymerase II, promoting apoptotic pathways with a predilection for metabolically active tissues that are dependent on high rates of protein synthesis such as the gastrointestinal tract, hepatocytes and proximal convoluted tubules.8, 9 This case describes a reversible AKI potentially related to psychedelic mushroom ingestion. As psilocybin prescribing becomes more widespread in Australia, clinical awareness of its potential renal effects is essential to ensuring patient safety. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.