This study aimed to evaluate the clinical findings in pediatric rhabdomyolysis and the predictive factors for acute kidney injury (AKI) in Korean children.
Medical records of 39 Korean children, who were newly diagnosed with rhabdomyolysis from January 2008 to December 2015, were retrospectively analyzed. The diagnosis was made from the medical history, elevated serum creatinine kinase level >1,000 IU/L, and plasma myoglobin level >150 ng/mL. Patients with muscular dystrophy and myocardial infarction were excluded.
The median patient age at diagnosis was 14.0 years (range, 3–18 years), and the male to female ratio was 2.5. The most common presenting symptom was myalgia (n=25, 64.1%), and 14 patients (35.9%) had rhabdomyolysis-induced AKI. Eighteen patients (46.2%) had underlying diseases, such as epilepsy and psychotic disorders. Ten of these patients showed rhabdomyolysis-induced AKI. The common causes of rhabdomyolysis were infection (n=12, 30.7%), exercise (n=9, 23.1%), and trauma (n=8, 20.5%). There was no difference in the distribution of etiology between AKI and non-AKI groups. Five patients in the AKI group showed complete recovery of renal function after stopping renal replacement therapy. The median length of hospitalization was 7.0 days, and no mortality was reported. Compared with the non-AKI group, the AKI group showed higher levels of peak creatinine kinase and myoglobin, without statistical significance.
The clinical characteristics of pediatric rhabdomyolysis differ from those observed in adult patients. Children with underlying diseases are more vulnerable to rhabdomyolysis-induced AKI. AKI more likely develops in the presence of a high degree of albuminuria.
Rhabdomyolysis is a syndrome characterized by skeletal muscle breakdown and leakage of muscle cell contents such as electrolyte, myoglobin, and other sarcoplasmic proteins into the circulation. It is caused by a wide variety of diseases such as trauma or direct injury, excessive muscle activity, hereditary muscle enzyme defects, infections, body temperature changes, drugs and toxins, and metabolic and endocrine disorders.
Acute kidney injury (AKI) is a common, severe complication of rhabdomyolysis, and roughly, 13%–46% of patients with rhabdomyolysis have been reported to develop AKI.
There are limited reports on the characteristics of and predictive factors for AKI in children with rhabdomyolysis. Our objectives were to (1) analyze the etiologies, clinical manifestations, and the prevalence of AKI and (2) establish the predisposing factors of AKI using the clinical and biochemical data in pediatric patients with rhabdomyolysis.
The medical records of 39 pediatric patients with rhabdomyolysis who attended Samsung Medical Center, a tertiary referral center located in Seoul, Republic of Korea, between January 2004 and December 2015 were retrospectively reviewed. All data were obtained from electronic medical records in accordance with the ethical principles for medical research involving human subjects established in the Helsinki Declaration of 1975 and revised in 2000. The Institutional Review Board (IRB) of Samsung Medical Center (approval number: 2016-03-158) approved this study. Obtaining of written informed consent was exempted from IRB. The clinical data including age, sex, associated symptoms and signs (fever, myalgia, muscle weakness, dark urine, and history of previous infection), the amount of fluid administered during admission, bicarbonate therapy, need for renal replacement therapy, length of hospital stay, and outcomes were collected from the electrical medical records. The laboratory data including initial serum hemoglobin, white blood cell count, platelet, blood urea nitrogen, serum creatinine, calcium, phosphorous, electrolyte, lactic dehydrogenase, alanine and aspartate aminotransferase levels, uric acid, CK, myoglobin, and urinalysis were also obtained from the medical records. The levels of serum CK and myoglobin were checked at admission and every 24 hours until the levels were normalized.
Rhabdomyolysis was diagnosed on the basis of medical history and laboratory findings including elevated serum CK levels >1,000 IU/L and serum myoglobin >150 ng/mL. The elevations in CK were not caused by myocardial infarction or inflammatory myopathies. The definition of AKI was based on the Kidney Disease Improvement Global Outcomes guideline.
Continuous data were presented as medians and interquartile ranges, and categorical data were presented as absolute frequencies. Continuous data were analyzed by Wilcoxon signed rank test while categorical data were analyzed by Fisher exact test to compare between the groups. A multivariate logistic regression analysis was used to assess the independent predictors for AKI. A receiver operating characteristics (ROC) curve analysis was used to assess the sensitivity and specificity of the prediction of AKI.
The demographic data are presented in
The most common presenting symptom was myalgia, and the number of children with dark urine was relatively small. The most common etiology was infection, and 14 children showed the symptoms and signs of viral infection before the development of rhabdomyolysis. The confirmed pathogens included adenovirus, parainfluenza type 1, and
Depending on the patient's condition, patients received the intravenous hydration with a total daily input of 1,600 to 3,000 mL/m2 as the initial treatment, and 3 patients subsequently underwent urine alkalization. The ratio of non-AKI to AKI was 1.7, and 8 patients proceeded to AKI Stage 3. Among 14 patients with AKI, 5 patients received CRRT. Among 5 patients with CRRT, four patients had underlying disease and received sodium bicarbonate therapy. The characteristics of each patient are shown in
Our results suggested that the etiologies and clinical manifestations of pediatric rhabdomyolysis were different from those of adults. A previous study conducted in adults reported that a single factor or combinations of alcohol, muscle pressure, traumatic muscle injury, metabolic disorder, and hypothermia might cause rhabdomyolysis in adult patients. In Korean adults, traumatic muscle injury was the most common cause of rhabdomyolysis.
Our findings were compatible with those of the previous study. It has been reported that approximately half of the patients with rhabdomyolysis present with the triad of myalgia, weakness, and dark urine, and pediatric patients usually presented with muscle pain, fever, and other symptoms associated with viral infection rather than dark urine. According to our results, the triad of symptoms is uncommon in pediatric rhabdomyolysis. In our study, the male to female ratio was 2.5:1, and this finding was similar to the previously reported data in which the male to female ratio ranged from 2:1 to 4:1.
According to previous reports, the outcomes vary widely, and the incidence of AKI in pediatric patients with rhabdomyolysis varied from 5% to 50%.
Increased myoglobin and CK as a consequence of muscular cell death are the major laboratory findings, and there have been a few reports that evaluated the association between the levels of CK and myoglobin, and the development of AKI. In previous studies, the levels of CK and myoglobin have been used as an appropriate index for diagnosis and severity, and peak levels of CK were suggested as a predictive factor of AKI in adults. Kasaoka et al.
In our study, CRRT was effective in reducing the value of serum CK and myoglobin, and patients who received CRRT showed complete recovery of renal function. According to the previous data, 66% of the patients with AKI caused by rhabdomyolysis died.
There are a few limitations to this study. This is a single, referral center study, and there is a possibility that children with morbidity were enrolled in the study. This condition could affect the clinical manifestations and outcomes. Additionally, this is a retrospective study, and the peak levels of CK and myoglobin might be incorrect.
In conclusion, the clinical manifestations of pediatric rhabdomyolysis are different from those of the condition in adults, and AKI is more likely to develop in the presence of a high degree of albuminuria and underlying diseases in children with rhabdomyolysis.
Variable | Value |
---|---|
Median age at the time of diagnosis (yr) | 14.0 |
Male to female ratio | 2.5:1 |
Underlying disease | 18 (46.2) |
Causes of rhabdomyolysis | |
Infection | 12 (30.7) |
Exercise | 9 (23.1) |
Trauma | 8 (20.5) |
Ischemia | 4 (10.3) |
Drug | 4 (10.3) |
Seizure | 2 (5.1) |
Presentations of rhabdomyolysis | |
Myalgia | 25 (64.1) |
Muscle weakness | 12 (30.7) |
Dark urine | 7 (17.9) |
Acute kidney injury | |
Stage 1 | 4 (10.3) |
Stage 2 | 2 (5.1) |
Stage 3 | 8 (20.5) |
Renal replacement therapy | 5 (12.8) |
Median length of hospitalization (day) | 7 |
Progression to chronic kidney disease | 0 (0) |
Mortality | 0 (0) |
Values are presented as number (%) unless otherwise indicated.
No. | Age (yr) | Sex | Underlying diseases | Etiology | LOS (day) | Peak CK (IU/L) | Peak myoglobin (ng/mL) | CRRT (day) | Comment |
---|---|---|---|---|---|---|---|---|---|
1 | 10 | F | Duodenal obstruction | Exercise | 5 | 5,165 | 6,085 | 2.8 | Daily 4 to 5 hours roller skating during 1 weeks |
Incidentally detected duodenal obstruction | |||||||||
2 | 10 | M | Tourette syndrome | Infection | 26 | 8,566 | 328 | 1.7 | Sepsis with hepatitis |
Intravenous antibiotics therapy for 4 weeks | |||||||||
3 | 14 | F | Previous healthy | Infection | 22 | 2,425 | 602.65 | 10 | Mycoplasma pneumonia, ARDS |
ECMO therapy for 1 weeks | |||||||||
4 | 18 | F | Cranioparyngioma | Infection | 54 | 209,057 | 20,000 | 14.6 | Adrenal crisis with adenovirus infection |
Post intermittent hemodialysis for 1 weeks | |||||||||
5 | 18 | M | Marfan syndrome | Ischemia | 51 | 1,997 | 1,817 | 8 | Cardiac operation for mediastinal hematoma, pseudoaneurysm with Marfan syndrome |
Post intermittent hemodialysis for one cycle |
LOS, length of hospitalization; CK, creatinine phosphokinase; ARDS, acute respiratory distress syndrome; ECMO, extracorporeal membrane oxygenation.
Variable | AKI group | Non-AKI group | |
---|---|---|---|
No. of patients (%) | 14 (35.9) | 25 (64.1) | |
Age (yr) | 14 | 14 | 0.386 |
Sex, male:female | 7:7 | 21:4 | 0.033 |
Presenting symptoms | |||
Muscle pain | 8 (20.5) | 17 (43.6) | 0.512 |
Muscle weakness | 6 (15.4) | 6 (15.4) | 0.287 |
Dark urine | 2 (5.1) | 5 (12.8) | 1.000 |
Etiology of rhabdomyolysis | |||
Infection | 5 (35.77) | 7 (28) | |
Exercise | 3 (21.4) | 6 (24) | |
Trauma | 2 (14.3) | 6 (24) | |
Ischemia | 2 (14.3) | 2 (8) | 0.964 |
Drug | 1 (7.1) | 2 (8) | |
Seizures | 1 (7.1) | 1 (4) | |
Unknown | 0 (0) | 1 (4) | |
Length of hospitalization (day) | 20 | 4 | 0.091 |
Values are presented as number (%) unless otherwise indicated.
Variable | AKI group | Non-AKI group | |
---|---|---|---|
Body mass index (kg/m2) | 21.8 | 19.2 | 0.193 |
WBC count, blood (×103/µL) | 9,840 | 9,530 | 0.203 |
BUN (mg/dL) | 26.5 | 12.1 | 0.028 |
eGFR (mL/min/1.73m2) | 40.2 | 100.4 | 0.002 |
Serum AST (IU/L) | 193 | 96 | 0.299 |
Serum ALT (IU/L) | 95 | 53 | 0.198 |
Serum uric acid (mg/dL) | 7.4 | 5.2 | 0.072 |
Sodium (mmol/L) | 140 | 140 | 0.848 |
Potassium (mmol/L) | 4.4 | 4.1 | 0.318 |
Peak levels of CK (IU/L) | 6,750.5 | 4,995 | 0.781 |
Peak myoglobin (ng/mL) | 2,945 | 860 | 0.156 |
Urine blood (0–4+), mean (range) | 4+ (2+ to 4+) | 1+ (0 to 4+) | 0.053 |
Urine albumin (0–4+), mean (range) | 1+ (0 to 2+) | 0 (0 to 1+) | 0.012 |
Bicarbonate therapy | 7 | 3 | 0.019 |
WBC, white blood cell; BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate; aspartate aminotransferase; ALT, alanine aminotransferase; CK, creatinine phosphokinase.