Acute kidney damage occurs less frequently in patients with exercise-induced muscle loss than previously thought

New study from Kaiser Permanente shows that patients with elevated creatine kinase levels due to strenuous exercise – “rhabdo” – had a higher risk of kidney damage if they took NSAIDs or were dehydrated

A new study by researchers at Kaiser Permanente published in JAMA Network Open challenges the long-held belief that all patients with exercise-induced rhabdomyolysis, or “rhabdo,” whose blood tests show elevated levels of the enzyme creatine kinase (or CK) are at risk for acute kidney failure—when the kidneys suddenly stop working—and need to be hospitalized.

Occasionally, people who do long or intense bouts of exercise can develop exercise-induced rhabdomyolysis, which is when muscle tissue breaks down and enters the bloodstream. The symptoms – severe muscle cramps, pain, stiffness and discolored urine – can send people to the emergency room. Doctors test these patients' blood to see if they have high levels of creatine kinase, an enzyme that enters the blood when muscle cells break down.

“People with exercise-induced rhabdomyolysis and high creatine kinase levels are typically hospitalized because doctors are concerned about their risk of developing acute kidney failure,” said lead study author Amir Sabouri, MD, PhD, a neurologist with the Permanente Medical Group. “Our study found that patients with exercise-induced rhabdomyolysis who were not found to have acute kidney failure on the initial tests performed when they were admitted to the emergency department did not subsequently develop it. This suggests that additional testing and treatment, as well as longer hospital stays, may not be necessary for these patients.”

We believe our findings will change the way physicians think about the association between creatine kinase and acute renal failure in these patients.

— Amir Sabouri, MD, PhD

The new study is the largest to date to look at the factors that increase the risk of acute kidney failure in patients with exercise-induced rhabdomyolysis. It included 200 adults who were hospitalized at Kaiser Permanente Northern California hospital between 2009 and 2019 after being diagnosed with the condition in the emergency department. All patients had engaged in strenuous physical activity within 48 hours before hospital admission. The study found that only 17 (8.5%) of the 200 patients developed acute kidney failure.

“The results of this study provide important data that show us that the way we have been treating patients with rhabdomyolysis in the emergency department may not be appropriate for most patients,” said Dana Sax, MD, an associate investigator in Kaiser Permanente's Division of Research and an emergency physician at TPMG. “These results may surprise many providers and should encourage shared decision-making discussions with patients about whether hospitalization is truly in the patient's best interest.”

The research team reviewed the patients' medical records to identify factors that differentiated those with acute kidney failure from those without. The study found that, contrary to popular belief among clinicians, there is no association between high creatine kinase levels and an increased risk of acute kidney failure. Factors such as age, gender, race or ethnicity, body mass index, previous diagnoses of diabetes or high blood pressure, and the type of exercise that leads to exercise rhabdomyolysis also showed no association.

The study found an association between pre-admission dehydration and a history of taking non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen and naproxen. (These drugs are known to be associated with the development of acute renal failure, particularly in patients with other risk factors.)

Exercise-induced rhabdomyolysis remains relatively rare. Researchers reviewing U.S. emergency department records identified 40,654 patients admitted with exercise-induced rhabdomyolysis between 2000 and 2019. However, there was a 10-fold increase between the first and second decades; the reason is unknown. The highest incidence was seen in young adult men and black adults. During the 10-year period of this new study, the incidence of hospitalizations for exercise-induced rhabdomyolysis increased by 0.38 to 0.97 cases per 100,000 population, consistent with the national trend.

“We believe our findings will change the way physicians think about the relationship between creatine kinase and acute kidney failure in these patients,” Sabouri said. “I decided to do this study because I had patients with exercise-induced rhabdomyolysis and we didn't have enough clear information to make treatment decisions, understand the risk of kidney failure, or know when to admit or discharge patients. With this study, we now have this important information.”

The researchers said that educating athletes to drink plenty of fluids and to use acetaminophen rather than an NSAID for pain relief could help prevent people who develop exercise-induced rhabdomyolysis from developing acute kidney injury. In fact, the study suggests that 92.6% of acute kidney injury could have been prevented if patients had not been dehydrated or taken an NSAID.

“Pain is a signal that athletes need to be aware of,” said TPMG lead nephrologist Siamack Nemazie, MD. “NSAIDs can mask that pain, making it more likely that someone will continue to exercise. And if they are not adequately hydrated, that can set the stage for exercise-induced rhabdomyolysis. Every patient I have seen in the outpatient setting or in the emergency department with this condition has been someone who was overexerting themselves and not staying adequately hydrated.”

And the concern goes beyond athletes. “Our findings are also relevant for fire and police academies, the military, the field of sports medicine, and fitness and corporate health programs,” Sabouri said. “In all of these situations, it is possible that people are participating in strenuous exercise that can lead to acute kidney failure. Our message to them is: drinking plenty of water and not taking NSAIDs can prevent acute kidney failure.”

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, of The Permanente Medical Group; Yun-Yi Hung, PhD, of the Department of Research; and Jafar Kafaie, MD, PhD, of St. Louis University.

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About Kaiser Permanente Research

The Kaiser Permanente Division of Research conducts, publishes, and disseminates epidemiological and health services research to improve the health and health care of Kaiser Permanente members and the community at large. It seeks to understand the determinants of disease and well-being and to improve the quality and cost-effectiveness of health care. DOR's more than 600 employees are currently working on more than 450 epidemiological and health services research projects. For more information, visit divisionofresearch.kaiserpermanente.org or follow us at @KPDOR.