The best questions often stem from the inquisitive learner. As educators, we love—and are always humbled—by those moments when we get to say “I don’t know.” For some of these questions, you may already know the answers. For others, you may never have thought to ask the question. For all, questions, comments, concerns, and critiques are encouraged. Welcome to the Kids Korner.

Question

“In children with influenza, muscle pain, and an elevated serum creatine kinase (CK), is there a specific CK level that predicts acute kidney injury or renal failure and warrants admission for continued inpatient hydration?”

It feels like it has been a busier influenza season this year. You may have seen one or two … or a thousand of them. Anecdotally, at our location, it feels like myositis and rhabdomyolysis associated with influenza didn’t really rear its head until later in the flu season. Maybe it was this strain of influenza? Maybe it was our location? Maybe it’s recall bias? Anyway, that association prompted this question.

Rhabdomyolysis is rapid muscle tissue breakdown that results in elevated levels of serum creatine kinase (CK) and can lead to systemic injuries such as acute kidney injury (AKI) and electrolyte imbalances. In adults, there is a scoring system—the McMahon score—that predicts the likelihood of mortality or acute kidney injury (AKI) in patients with rhabdomyolysis patients. The McMahon score incorporates age, sex, and electrolytes abnormalities in addition to CK results.¹

The RIFLE criteria are another system that has been explored to predict the severity and prognosis of AKI in adults.² For children, though, we are unfamiliar with any similar scoring system. The question arises “Is there a particular CK value that predicts an AKI in children with myositis/rhabdomyolysis from influenza?” While every case has other factors that contribute to our decision-making that should be considered, is there a specific CK value that we should really take note of? We’re only seeking to evaluate viral-induced myositis/ rhabdomyolysis and not rhabdomyolysis caused by other etiologies such as trauma or heart disease.

We were unable to find any strong conclusion on a specific CK level or its prognosis for AKI in children. Most pediatric studies on rhabdomyolysis were retrospective, had small numbers, and included variable causes of rhabdomyolysis. For instance, a 2000 retrospective study by Watemberg et. al., identified 19 children with rhabdomyolysis over an 8-year period.³ The most common causes were trauma (5), non-ketotic hyperosmolar coma (2), viral myositis (2), dystonia (2), and malignant hyperthermia.² Additionally, the study found that “coma” occurred in 7 patients, suggesting an extremely sick patient population. Even with the variation in etiology and severity of illness, though, the authors stated, “There was no significant difference in serum creatine kinase levels in patients with versus without acute renal failure.” However, it is a single small study and thus is difficult to draw any real conclusions.

Fast forward a few years to another retrospective study of 28 children with a mean age of 11.1 plus or minus 5.6 years (median 12.5 years old).⁴ The most common cause of rhabdomyolysis was infection (43 percent), exertional (25 percent), trauma (10.7 percent), unknown (10.7 percent), DKA (3.6 percent), seizures (3.6 percent), and toxin from spider bite (3.6 percent). All the patients were admitted to the hospital and the authors sought to determine what factors were associated with acute renal failure requiring dialysis. CK, IV fluid bolus administration, use of sodium bicarbonate fluids, and electrolytes were among the values recorded. Those who received an IV fluid bolus were less likely to require dialysis, but the number was not statistically significant. Seven of the 28 children required dialysis. The authors did not find any significant difference in admission or peak CK levels among those who did versus did not require dialysis. They did mention, though, that all the patients who required dialysis had a peak CK level greater than 5000 U/L. While the results are interesting, they don’t really address the ED setting, as all the patients were admitted patients with variable causes of rhabdomyolysis. Perhaps a CK of 5,000 U/L is an important number and provides a hopping-off point for discussion.

A separate 2013 retrospective ED study by Chen et. al., also identified 5000 U/L as a number with increased probability of developing acute renal failure.⁵ It’s difficult to draw any true conclusions related to children, as only 20 percent of the study participants were children and the overall predominant causes of rhabdomyolysis were trauma (27 percent) and infection (18 percent). There was another inpatient 10-year retrospective study in Taiwan that looked at 172 children with rhabdomyolysis.⁶ The mean age was 7.3 years old. The most common cause of rhabdomyolysis was viral myositis (72 percent). Although limited by the non-ED setting, the authors identified some factors associated with acute renal failure. They include: an elevated serum CK, elevated serum AST, and an elevated serum myoglobin. The serum CK in those with and without acute renal failure was 20,780 versus 7,124 IU/L, respectively, so a higher number seemed to be associated with renal failure, but there was no magic number.

A more recent study from 2021 by Kuok et. al., retrospectively identified 54 children with a median age of 7.8 years old who were admitted for rhabdomyolysis.⁷ Again, it’s an inpatient study. Most of the rhabdomyolysis was caused by viral myositis (72 percent), though, which is good for looking at our question of interest. The peak CK in children who did versus did not develop AKI was 23,086 versus 3,960 IU/L, respectively. The peak values were recorded over the first 72 hours of admission. Specifically on admission, though, the CK level for the two groups was 2,727 and 3,014, respectively—so it was not significantly different. An AKI developed in 18.5 percent of the children and just two children warranted dialysis. In general, those that developed an AKI seemed to be more dehydrated with obvious signs of rhabdomyolysis on the urine dipstick test and the presence of metabolic acidosis. Another 10-year, retrospective 23-hospital multicenter study in South Korea found similar results. In that study of 880 inpatient admitted children with rhabdomyolysis, there was no significant difference in admission CK levels in children who did and did not develop an AKI—3,161 versus 1,986 U/L—respectively.⁸ It was more about the overall clinical picture of dehydration, associated elevation in AST, urinary abnormalities, and the presence of an AKI at presentation. It appears that a specific screening CK level is less important than the overall clinical picture of the child. Still no magic number.

Now on to some pediatric studies specifically in the ED setting. The first was an eight-year retrospective study at two Italian pediatric EDs and included 113 children ages 2 to 13.2 years old (median 6 years old).⁹ Specifically, the authors were interested in evaluating benign acute childhood myositis (BACM)—which is a viral-induced myositis that typically affects the calves and is associated with an elevated serum CK level. This is the group that we are specifically interested in with our question today. The most common viral illness in the study was influenza. Children were hospitalized in 85 percent (96/113) of the cases in this study. No one required dialysis or had significant electrolyte abnormalities observed during their admission. The median age was 6 years old and the median serum CK level at admission was 1,413 IU/L with a range of 257 to 12,858 IU/L. That’s a large range of serum CK values but all children had a benign course and excellent clinical outcome. Another 2018 retrospective study of 54 children with benign acute childhood myositis had similar results (n=54).¹⁰ The mean age was 7.4 years old with a mean initial CK of 1,872 I/U (median 2207 IU/L) at admission. No patients developed an AKI or developed renal failure. In this study, an AKI was defined as an increase in serum Cr concentration of 50 percent or more from baseline. Again, this study supports a benign disease process where there is no particular CK cut-off value that suggests concern for the development of an AKI or renal failure. The highest serum CK in the study was 8,086 IU.

Conversely, though, a final study of benign acute childhood myositis suggests a different outcome.¹¹ It was a four-year retrospective study that included 114 children with a median age of 7 years old. The median CK was 3,332 IU/L (range 427 to 50,185). Unlike the prior studies, two of these patients did develop acute renal failure and the study only admitted 23 percent of the patients. All patients in the ED got IV fluid rehydration and alkalization of urine—which may not regularly happen in all ED settings. Acute renal failure occurred in two patients who both demonstrated serum CK levels greater than 20,000 IU/L. Both these patients reportedly appeared sick. In general, this does suggest that, overall, the disease is benign—but acute renal failure can and does occasionally occur.

Summary

There is no specific elevated CK value in viral-induced myositis/rhabdomyolysis that suggests the development of acute renal failure. Many children develop elevated CK levels in the 3,000 IU/L range with good outcomes. The overall clinical picture of the patients appears to be the best indicator. Myositis associated with elevated CK levels in the setting of viral illnesses (particularly influenza) is referred to as Benign Acute Childhood Myositis. Acute renal failure can occur, but it is very uncommon.

Dr. Jones is associate professor at the department of emergency medicine & pediatrics and the program director of pediatric emergency medicine fellowship at the University of Kentucky in Lexington, Kentucky.

Dr. Cantor is the emeritus medical director for the Central New York Poison Control Center and professor of emergency medicine and pediatrics in Syracuse, New York.

References

1. Simpson JP, Taylor A, Sudhan N et al. Rhabdomyolysis and acute kidney injury: creatinine kinase as a prognostic marker and validation of the McMahon score in a 10-year cohort: a retrospective observational evaluation. Eur J Anaesthesiol. 2016 Dec; 33(12):906-912.
2. Delaney KA, Givens ML, Vohra RB. Use of RIFLE criteria to predict the severity and prognosis of acute kidney injury in emergency department patients with rhabdomyolysis. J Emerg Med. 2012 May; 42(5):521-8.
3. Watemberg N, Leshner RL, Armstrong BA et al. Acute pediatric rhabdomyolysis. J Child Neurol. 2000 Apr; 15(4):222-7.
4. Zapeda-Orozco D, Ault BH, Jones DP. Factors associated with acute renal failure in children with rhabdomyolysis. Pediatr Nephrol. 2008 Dec; 23(12):2281-4.
5. Chen CY, Lin YR, Zhao LL et al. Clinical factors in predicting acute renal failure caused by rhabdomyolysis in the ED. Am J Emerg Med. 2013 Jul; 31(7):1062-6.
6. Wu CT, Huang JL, Lin JJ et al. Factors associated with nontraumatic rhabdomyolysis and acute renal failure of children in Taiwan population. Pediatr Emerg Care. 2009 Oct; 25(10):657-60.
7. Kuok CI, Chan WKY. Acute kidney injury in pediatric non-traumatic rhabdomyolysis. Pediatr Nephron. 2021 Oct; 36(10):3251-3257.
8. Yoo S, Cho MH, Baek HS et al. Characteristics of pediatric rhabdomyolysis and the associated risk factors for acute kidney injury: a retrospective multicenter study in Korea. Kidney Res Clin Pract. 2021 Dec; 40(4):673-686.
9. Brisca G, Mariani M, Pirlo D et al. Management and outcome of benign acute childhood myositis in pediatric emergency department. Ital J Pediatric. 2021 Mar 9; 47(1):57.
10. Rosenberg T, Heitner S, Scolnik D et al. Outcome of benign acute childhood myositis: the experience of 2 large tertiary care pediatric hospitals. Pediatr Emerg Care. 2018 Jun; 34(6):400-402.
11. Turan C, Yurtseven A, Cicek C et al. Benign acute childhood myositis associated with influenza A/B in the paediatric emergency department and the efficacy of early-onset oseltamivir. J Paediatr Child Health. 2022 Jun; 58(6):1022-1027.