New Kaiser Permanente study finds patients with high creatine kinase levels from strenuous exercise — “rhabdo” — had higher risk of kidney injury if they used NSAIDs or were dehydrated
A new study by Kaiser Permanente researchers published in JAMA Network Open calls into question the long-standing belief that all patients with exertional rhabdomyolysis or “rhabdo” whose blood tests reveal high levels of the enzyme creatine kinase (or CK) are at risk of acute kidney injury — when the kidneys suddenly stop working — and need to be hospitalized.
On occasion, people who take part in long or intensive exercise sessions can develop exertional rhabdomyolysis, a condition that occurs when muscle tissue breaks down and enters the blood stream. Its symptoms — severe muscle cramps, pain, stiffness, and discolored urine — can bring people to the emergency room. Doctors test these patients’ blood to see if they have high levels of creatine kinase, one of the enzymes that leaks into the blood when muscle cells break open.
“People with exertional rhabdomyolysis who have high creatine kinase levels are typically hospitalized because doctors are concerned about their risk of developing acute kidney injury,” said the study’s lead author Amir Sabouri, MD, PhD, a neurologist with The Permanente Medical Group. “Our study found that if patients with exertional rhabdomyolysis didn’t have an acute kidney injury identified on the initial tests that were done when they were admitted to the emergency department, they didn’t develop one later. This suggests that extra tests and treatments and longer hospital stays might not be needed for these patients.”
We believe our findings will change the way physicians think about the relationship between creatine kinase and acute kidney injury in these patients.
— Amir Sabouri, MD, PhD
The new study is the largest to date to look at the factors that increase risk for acute kidney injury in patients with exertional rhabdomyolysis. It included 200 adults who were hospitalized in Kaiser Permanente Northern California between 2009 and 2019 after being diagnosed in the emergency department with this condition. All the patents had engaged in strenuous physical activity within 48 hours of hospitalization. The study found that only 17 (8.5%) of the 200 patients developed acute kidney injury.
“The findings from this study provide important data that tell us the way that we have historically managed patients with rhabdomyolysis in the emergency department may not be indicated for most patients,” said Dana Sax, MD, an adjunct investigator with the Kaiser Permanente Division of Research and TPMG emergency medicine physician. “These findings may surprise many providers and should promote shared decision-making conversations with patients about whether hospitalization is really in the patient’s best interest.”
The research team reviewed the patients’ medical records to identify factors that differentiated the patients who developed acute kidney injury from those who did not. The study found that, contrary to common belief among clinicians, there was no association between high creatine kinase levels and an increased risk of acute kidney injury. Factors such as age, gender, race or ethnicity, body mass index, previous diagnoses of diabetes or hypertension, and type of exercise leading to exertional rhabdomyolysis also showed no association.
The study did identify an association between pre-admission dehydration and a history of using non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and naproxen. (These medications are known to be associated with the development of acute kidney injury, especially in patients with other risk factors.)
Exertional rhabdomyolysis remains relatively rare. Researchers reviewing U.S. emergency department records identified 40,654 patients admitted from 2000 to 2019 with exertional rhabdomyolysis. However, there was a 10-fold increase from the first to the second decade; the reason is not known. The highest incidence was seen in young adult males and Black adults. During the 10-year period in this new study, the incidence of hospitalization for exertional rhabdomyolysis increased 0.38 to 0.97 cases per 100,000 population, reflecting the national trend.
“We believe our findings will change the way physicians think about the relationship between creatine kinase and acute kidney injury in these patients,” said Sabouri. “We decided to do this study because we had patients with exertional rhabdomyolysis, and we didn’t have enough clear information to help us make treatment decisions, understand the risk of kidney injury, or know when to admit or discharge patients. Now, with this study, we have that important information.”
The researchers said that educating athletes to stay hydrated and to use acetaminophen for pain relief rather than an NSAID could help keep people who develop exertional rhabdomyolysis from developing acute kidney injury. In fact, the study suggests that 92.6% of acute kidney injuries could have been prevented if the patients had not been dehydrated or taken NSAIDs.
“Pain is a signal that athletes need to pay attention to,” said senior author TPMG nephrologist Siamack Nemazie, MD. “NSAIDs can mask that pain, which makes it more likely that someone will continue to exercise. And if they are not sufficiently hydrated it can set the stage for exertional rhabdomyolysis. Every patient I have seen outpatient or in the emergency department with this condition has been someone pushing themselves too hard who has not stayed hydrated.”
And the concern goes beyond athletes. “Our findings are also relevant to fire and police academies, the military, the field of sports medicine, and fitness and corporate wellness programs,” said Sabouri. “In all these situations, it’s possible for people to take part in strenuous exercise that could lead to acute kidney injury. The message we have for them is this: Drinking a lot of water, and not taking NSAIDs, can prevent acute kidney injury.”
The study was funded by the Kaiser Permanente Northern California Community Health Program.
Co-authors include Brian Yurgionas, MD, MS, Sara Khorasani, MD, Jeffery G. Klingman, MD, and Edward J. Durant, MD, MPH, with The Permanente Medical Group; Yun-Yi Hung, PhD, with the Division of Research; and Jafar Kafaie, MD, PhD, with St Louis University.
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About the Kaiser Permanente Division of Research
The Kaiser Permanente Division of Research conducts, publishes and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and society at large. It seeks to understand the determinants of illness and well-being, and to improve the quality and cost-effectiveness of health care. Currently, DOR’s 600-plus staff is working on more than 450 epidemiological and health services research projects. For more information, visit divisionofresearch.kaiserpermanente.org or follow us @KPDOR.
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