Laboratory Studies
The most important laboratory test is measurement of creatine kinase (CK) levels to assess for rhabdomyolysis. Myoglobin is the first enzyme that increases, but it returns to normal levels within the first 24 hours after the onset of symptoms. This is because myoglobin is rapidly cleared from the serum into the urine. However, serum CK levels may remain elevated after serum and urine test results for myoglobin have become negative. Serum CK levels typically peak about 3 days after the onset of symptoms, and remain elevated for several days. Thus, although the detection of myoglobin in the serum is considered pathognomonic for rhabdomyolysis, the serum CK level is a more useful marker for the diagnosis and assessment of severity because of its delayed clearance from the plasma. A CK level of more than 1000 U/L is characteristically seen in patients with rhabdomyolysis. [4, 7] Levels of other muscle enzymes, such as aldolase, lactate dehydrogenase (LDH), or aspartate aminotransferase (AST), may also be elevated.
Electrolyte abnormalities may cause or result from rhabdomyolysis, including hyperkalemia and hyperphosphatemia from the damaged muscle cells. Hypocalcemia may develop from the hyperphosphatemia or as result of calcium deposition in the damaged muscles. Uric acid values may be elevated, and metabolic acidosis may develop.
Acute renal insufficiency (elevated BUN and creatinine levels) is a consequence of severe myoglobinuria in which the globulin precipitates and blocks the urinary tubules. Creatinine levels may be elevated out of proportion to BUN levels due to excessive leak of creatine from damaged muscle cells. Alkalinization of the urine and increased urine flow facilitates myoglobin excretion.
Although both myoglobinuria and hemoglobinuria may cause a tea-colored appearance of the urine, and although both cause positive results on the urine dipstick for blood, myoglobinuria may be differentiated from hemoglobinuria by performing a series of simple tests. [18] Myoglobinuria is brown, and often only a few RBCs are present in the urine. Hematuria produces a reddish sediment in spun urine samples. Red or brown urine with a negative dipstick result for blood indicates a dye in the urine. Hemoglobin produces a reddish or brown coloration in the spun serum, whereas myoglobin does not discolor the serum. CK levels are markedly elevated in myoglobinuria. Results of radioimmunoassays for the specific measurement of serum or urine myoglobin can be delayed by several days and are not useful in immediate diagnosis and treatment.
Other electrolytic abnormalities associated with rhabdomyolysis result from the extrusion of intracellular contents into the plasma and include hyperkalemia, hypercalcemia or hypocalcemia, hyperphosphatemia, and hyperuricemia.
Imaging Studies
Imaging studies are rarely of use in this metabolic disorder.
Intravenous (IV) pyelograms may reveal a dense renogram, but most are normal.
Other Tests
Tests for sickle cell disease (eg, sickle preparations, hemoglobin electrophoresis) may reveal patients who are prone to rhabdomyolysis. A study by Nelson et al found that sickle cell trait was associated with a higher risk of exertional rhabdomyolysis (similar to the risk associated with tobacco use) among 47,944 soldiers who had undergone testing for hemoglobin AS. [19]
A drug and metabolic screen of the urine, blood, or both may indicate illicit drug use.
Complements and antinuclear antibodies may help in differentiating autoimmune polymyositis from other conditions.
In patients with acute renal insufficiency due to myoglobinuria, fractional excretion of sodium (FENa) is less than 1%, probably because tubular obstruction and damage is the cause of oliguria rather than glomerular damage.
Procedures
Muscle biopsy may be of use when a metabolic myopathy is suspected.
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Model of helical domains in myoglobin.
