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Sixteen cases of acute kidney injury following the use of synthetic cannabinoids were identified in the United States in 2012, according to a report from the Centers for Disease Control and Prevention.
The cases, which occurred in six states and were unrelated in all but two incidents, underscore the importance of awareness on the part of health care providers about renal and other unexpected toxicities from the use of synthetic cannabinoid (SC) compounds, the CDC said in the Feb. 15 issue of the Morbidity and Mortality Weekly Report.
Courtesy DEA
Synthetic marijuana
This is particularly true given the increasing use of SCs, also known as synthetic marijuana, "spice," or "K2, and in light of prior reports of toxicities associated with SC.
The initial four cases of acute kidney injury (AKI) following recent SC use were reported in Wyoming in March 2012, and an additional 12 cases were subsequently identified, including 6 in Oregon, 2 in New York, 2 in Oklahoma, and 1 each in Rhode Island and Kansas (MMWR 2013;62:93-8).
The patients – 15 adolescent or adult males aged 15-33 years, and one 15-year-old female – all visited emergency departments complaining of nausea and vomiting within days or hours of SC use; 12 also reported abdominal, flank, and/or back pain, and none had preexisting renal dysfunction or used medications associated with renal problems. All were hospitalized.
"The highest serum creatinine concentrations (creatinine peak) among the 16 patients ranged from 3.3 to 21.0 mg/dL (median: 6.7 mg/dL; normal 0.6-1.3 mg/dL) and occurred 1-6 days after symptom onset (median: 3 days)," according to the report.
Urinalysis results were variable, demonstrating proteinuria in eight patients, casts in five patients, white blood cells in nine patients, and red blood cells in eight patients. Renal ultrasonography in 12 patients showed that 9 had a nonspecific increase in renal cortical echogenicity. None had hydronephrosis.
Renal biopsy in eight patients demonstrated acute tubular injury in six cases, and features of acute interstitial nephritis in three.
Most patients experienced kidney function recovery within 3 days of creatinine peak, but five required hemodialysis, and four received corticosteroids.
Toxicologic analysis of the implicated SC product and clinical specimens were possible in seven cases, and two products were linked with the first three cases. These products contained 3-(1-naphthoyl) indole, a precursor to several aminoalkylindole synthetic cannabinoids, and one also contained AM 2201, a potent SC previously linked to human disease and death, but not to AKI.
With one exception, other product samples and/or blood or urine specimens from patients contained XLR-11 (a previously undescribed fluorinated-derivative of the known SC compound UR-144) either alone or in combination with an N-pentanoic acid metabolite of XLR-11 or UR-144.
These reports of AKI following SC use are concerning given the worldwide distribution of SC products, which are "packaged in colorful wrappers designed to appeal to teens, young adults, and first-time drug users," according to an editorial note in the report, which also states that SCs often are packaged with disingenuous labels claiming the products are not for human consumption, although it is widely known that they are smoked like marijuana.
Despite federal and state regulations prohibiting SC sale and distribution, illicit use continues, and reports of illness are increasing.
"The increasing use of synthetic cannabinoids in adolescents is particularly concerning because these substances can contain multiple active and inactive substances with a variety of short-term and potentially unknown long-term effects," Dr. Joanna S. Cohen said in an interview.
In a case study published last year, Dr. Cohen, of the departments of pediatrics and emergency medicine at George Washington University, Washington, noted the increasing use of SCs among adolescents, the potential dangers of SCs with respect to the developing brain, and the need for providers to become familiar with the presenting signs and symptoms of SC-related intoxication (Pediatrics 2012;129:e1064-7).
According to the MMWR report, SCs are related to the active ingredient in marijuana (delta-9-tetrahydrocannabinol), but are up to three times more likely to be associated with sympathomimetic effects such as tachycardia and hypertension, and about five times more likely to be associated with hallucinations.
An increase in seizure occurrence also has been reported with SC use.
"Given the rapidity with which new SC compounds enter the marketplace and their increasing use in the past 3 years, outbreaks of unexpected toxicity associated with their use are likely to increase," the CDC said.
Furthermore, no antidote currently exists; management of SC toxicity is symptomatic and supportive. All patients in this report of 16 cases of AKI recovered creatinine clearance during their hospital stay, but a risk for long-term kidney sequelae is possible. Findings from recent studies suggest the risk for chronic and end-stage renal disease is increased among patients who experience AKI, regardless of etiology and initial recovery.