Extremely High Creatine Kinase Activity in Rhabdomyolysis without Acute Kidney Injury

Background

Rhabdomyolysis is a medical condition that results from rapid breakdown and dissolution of damaged skeletal muscle fibers [1]. This condition is commonly secondary to physical trauma but can also be due to other etiologies such as muscle ischemia, toxin exposure, and muscle enzyme disorders [2]. Clinical indicators for rhabdomyolysis include myoglobinuria, fatigue, and myalgia, while laboratory indices for rhabdomyolysis include elevated creatine kinase (CK), lactate dehydrogenase (LDH), and serum myoglobin, and electrolyte imbalances such as hyperkalemia [2].

Patients demonstrate complications from rhabdomyolysis in a myriad of forms such acute kidney injury (AKI), electrolyte abnormalities, and disseminated intravascular coagulation [3]. While AKI is one of the most common and serious complications, patients with rhabdomyolysis require careful and thorough management to prevent it. Treatment modalities focus on AKI prevention by providing aggressive fluid resuscitation with either isotonic normal saline solution or sodium bicarbonate solution [3].

It is extremely rare for patients with severely high CK activity to have preserved kidney function. It is generally accepted that increasing CK activity in rhabdomyolysis is associated with higher incidence of AKI. This concept was adopted from at least 2 major observational studies of patients with rhabdomyolysis [4,5]. In these studies, patients with AKI had significantly higher CK activity compared to non-AKI patients with the highest peak CK activity of 55 000 U/L. Here, we present a rare case of a young patient with severe rhabdomyolysis and an exceptionally high CK activity (almost 3 times higher than in these studies) without AKI.

Case Report

INVESTIGATIONS:

CBC showed white blood cell count 8700/uL, hemoglobin 16.2 g/dL, hematocrit 46.2%, platelet count 180 000/uL. CMP showed serum sodium 134 mEq/L, serum potassium 4.2 mEq/L, serum chloride 98 mEq/L, serum bicarbonate 38.8 mEq/L, serum creatinine 0.77 mg/dL, blood urea nitrogen 14 mg/dL, serum magnesium 2.3 mg/dL, serum calcium 8.9 mg/dL, serum phosphate 3.5 mg/dL, AST 2299 U/L, ALT 404 U/L, CK >40 000 U/L, and LDH >12 000 U/L. Venous blood gas was sent due to elevated serum bicarbonate; pH of 7.411, and pCO2> 45.2 mmHg, suggesting chronic metabolic alkalosis with respiratory compensation due to intravascular volume contraction. Serum thyroid stimulating hormone (TSH) was insignificantly elevated at 5.655 uIU/mL. Urinalysis showed clear, dark amber urine, specific gravity 1.030, pH 6.3+ occult blood, 2+ protein, urine white blood cells 0–5, urine red blood cell 0–5. Daily laboratory results are illustrated in Table 1. With elevation of AST, ALT activity, an ultrasound of the liver was obtained and was negative for liver pathology. Elevation of AST and ALT activity were thought to be secondary to rhabdomyolysis.

Given the high suspicion for non-traumatic rhabdomyolysis, multiple studies were performed to identify the etiology. Urine drug screen was positive for cannabinoid and tricyclic agent. The latter could be a false positive from the cyclobenzaprine that he took prior to being hospitalized. Troponin I was 0.03 ng/mL (normal range, <0.03 ng/mL). Lyme IgG and IgM were negative. Hepatitis A antibody (HAV-IgM), hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc, IgG and IgM), and hepatitis C antibody (anti-HCV) were all negative. Human immunodeficiency virus (HIV) antibody was negative. Real-time polymerase chain reaction (PCR) of nasopharyngeal swab for influenza A/B virus was negative. Quantitative PCR for cytomegalovirus (CMV) was <200 IU/mL and for Epstein-bar virus (EBV) was <200 IU/mL. Screening anti-nuclear antibodies (ANA) by immunofluorescent assay was negative. Serum cystatin C level was sent as patient might have acute kidney injury with normal serum creatinine level. His serum cystatin C level was 0.57 mg/L with estimated glomerular filtration rate (eGFR) of 144 mL/min/1.73 m². Erythrocyte sedimentation rate (ESR) was normal at 6 mm/hour but C-reactive protein (CRP) was slightly elevated at 2.12 mg/dL (normal range, 0 to 1 mg/dL). Blood cultures showed no growth for 5 days. At this point, it was presumed that his rhabdomyolysis might be associated with marijuana abuse or a non-specific viral illness.

TREATMENT:

Patient was initially given 2 liters of normal saline solution followed by a maintenance infusion at 250 mL/hour. He was given 650 mg of acetaminophen every 8 hours as needed for severe myalgias. Fifteen mg of intravenous ketorolac was given with caution due to concern for renal impairment. He had been afebrile throughout hospital stay. CK activity and basic metabolic panel were followed daily as he was at high risk for acute kidney injury. On day 5 of hospitalization, elevated CK activity was confirmed by dilution method as >150 000 U/L. His myalgia had improved over the course of treatment. He did not require the use of acetaminophen and ketorolac within the 24 hours prior to discharge. His CK activity and LDH level slowly trended down to 32 042 U/L and 1609 U/L, respectively upon discharge. His serum creatinine level was 0.46 mg/dL on discharge.

OUTCOME AND FOLLOW-UP:

Patient was discharged after being hospitalized for 8 days. He was advised to continue taking oral fluid intake and follow up with his primary care physician.

Discussion

CONCLUSIONS:

Extremely high CK activity in rhabdomyolysis can lead to AKI. However, preserved kidney function is possible in such a patient. Young age, no concurrent cocaine use, and adequate oral fluid hydration may prevent AKI in rhabdomyolysis.