Acute kidney injury associated with smoking synthetic cannabinoid

Abstract

Context and objectives. Synthetic cannabinoids are illegal drugs of abuse known to cause adverse neurologic and sympathomimetic effects. They are an emerging health risk: 11% of high school seniors reported smoking them during the previous 12 months. We describe the epidemiology of a toxicologic syndrome of acute kidney injury associated with synthetic cannabinoids, review the toxicologic and public health investigation of the cluster, and describe clinical implications of the cluster investigation. Materials and methods. Case series of nine patients affected by the toxicologic syndrome in Oregon and southwestern Washington during May–October 2012. Cases were defined as acute kidney injury (creatinine > 1.3 mg/dL) among persons aged 13–40 years without known renal disease who reported smoking synthetic cannabinoids. Toxicology laboratories used liquid chromatography and time-of-flight mass spectrometry to test clinical and product specimens for synthetic cannabinoids, their metabolites, and known nephrotoxins. Public health alerts informed clinicians, law enforcement, and the community about the cluster and the need to be alert for toxidromes associated with emerging drugs of abuse. Results. Patients were males aged 15–27 years (median, 18 years), with intense nausea and flank or abdominal pain, and included two sets of siblings. Peak creatinine levels were 2.6–17.7 mg/dL (median, 6.6 mg/dL). All patients were hospitalized; one required dialysis; none died. No alternate causes of acute kidney injury or nephrotoxins were identified. Patients reported easily purchasing synthetic cannabinoids at convenience, tobacco, and adult bookstores. One clinical and 2 product samples contained evidence of a novel synthetic cannabinoid, XLR-11 ([1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone). Discussion and conclusion. Whether caused by direct toxicity, genetic predisposition, or an as-yet unidentified nephrotoxin, this association between synthetic cannabinoid exposure and acute kidney injury reinforces the need for vigilance to detect new toxicologic syndromes associated with emerging drugs of abuse. Liquid chromatography and time-of-flight mass spectrometry are useful tools in determining the active ingredients in these evolving products and evaluating them for toxic contaminants.

Keywords:

• Epidemiology
• Electronspray ionization
• Mass
• Public health
• Substance-related disorders
• Spectrometry

Acknowledgments

We thank Matthew Friesen, BA (Univ of California, San Francisco) for his meticulous processing of clinical and drug samples; Jeff Moran, PhD (K2 Consortium, Alabama Dept of Health), Tracy Murphy, DVM (Wyoming Dept of Health), Michael Schwartz, MD, and John Devlin, MD (CDC, National Center for Environmental Health/Agency for Toxic Substances and Disease Registry), and David Farrer, PhD (Oregon Public Health Division) for their invaluable consultation about synthetic cannabinoid toxicology; Alan Melnick, MD and Josh VanOtterloo, MPH (Public Health Department, Clark County, WA) for their assistance with patient investigation in Washington; Dan Sudakin, MD (Oregon State University) and Dan Petersen, PhD (University of California, Davis) for their consultation about plant nephrotoxins; Katrina Hedberg, MD, MPH, and Sean Schafer, MD, MPH (Oregon Public Health Division), for their assistance with initial study design and manuscript composition; Portland Drug Enforcement Agency (Multnomah County, Oregon) and Douglas County Interagency Narcotics Team (Douglas County, Oregon) for their collaboration; as well as patients and their families for trusting us with their stories.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official positions of the Oregon Public Health Division, University of California, or the Centers for Disease Control and Prevention.

Financial Disclosure: Dr. Buser was supported by the Epidemic Intelligence Service Fellowship through the Centers for Disease Control and Prevention. The remaining authors have no financial relationships relevant to this article to disclose.

Role of the Sponsor: The Centers for Disease Control and Prevention, Oregon Public Health Division, University of California, San Francisco, Douglas County Public Health, and Oregon Health & Sciences University had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.