ESSENTIALS OF DIAGNOSIS
Associated with crush injuries to muscle, immobility, drug toxicities, and hypothermia.
Characterized by serum elevations in muscle enzymes, including creatine kinase, and marked electrolyte abnormalities.
Release of myoglobin leads to direct renal toxicity.
Rhabdomyolysis is a syndrome of acute skeletal muscle necrosis leading to myoglobinuria and markedly elevated creatine kinase levels. ATN is a common complication due to filtration of excess myoglobin, which leads to tubular obstruction from pigmented casts and intrarenal vasoconstriction. Rhabdomyolysis can result from crush injuries, prolonged immobility, seizures, substance abuse (eg, cocaine), and medications (especially statins); concomitant volume depletion in these settings increases risk of rhabdomyolysis. The presence of kidney or liver disease, diabetes mellitus, and hypothyroidism increase the risk of rhabdomyolysis in patients taking statins. The cytochrome P450 liver enzymes metabolize all statins except for pravastatin and rosuvastatin. In patients taking statins, the risk of rhabdomyolysis is increased in the presence of kidney or liver disease, diabetes, or hypothyroidism. Concurrent use of statins (except pravastatin or rosuvastatin) and drugs that inhibit cytochrome P450 (including protease inhibitors, erythromycin or clarithromycin, itraconazole, diltiazem, and verapamil) as well as concurrent use of niacin and fibrate-containing therapy also increase the risk.
Patients with rhabdomyolysis may have myalgias or weakness or both, though it is not uncommon for them to be asymptomatic. Urine may appear dark.
Rhabdomyolysis of clinical importance commonly occurs when serum creatine kinase exceeds 16,000–50,000 IU/L; one study showed that 58% of patients with AKI attributed to rhabdomyolysis had creatine kinase levels greater than 16,000 IU/L, while only 11% of patients without AKI had creatine kinase values greater than 16,000 IU/L. Often, there are elevated serum levels of other skeletal muscle enzymes including AST, ALT, and LD. The acute, significant elevations in muscle enzymes peak quickly and usually resolve within days once the inciting injury has resolved.
The classic laboratory finding in rhabdomyolysis is a urine dipstick test that is positive for “blood” but without RBCs on microscopy; a false-positive result is due to detection of myoglobin rather than hemoglobin. Additionally, clinically meaningful rhabdomyolysis causes injured muscle cells to release intracellular components, leading to electrolyte derangements (including hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia).
The mainstay of treatment is aggressive volume repletion with 0.9% normal saline (ie, more than 4 L/day) and removal of offending medications if thought to have caused the disorder. Adjunctive treatments with mannitol and alkalization of the urine have not been proven to change outcomes in human trials. As patients recover, calcium can translocate from tissues to plasma, so early exogenous calcium administration for hypocalcemia is not recommended unless the patient is symptomatic or the level becomes exceedingly low ...