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MyoglobinuriaEdit

Myoglobinuria is the appearance of myoglobin, a muscle-derived heme protein, in the urine. It is usually a sign of significant skeletal muscle injury, though it can arise from a variety of conditions that cause muscle breakdown or abnormal handling of muscle contents. In practice, patients may notice dark, reddish-brown urine, and may report muscle pain, swelling, or weakness. The presence of myoglobin in urine is typically accompanied by a rise in muscle injury markers such as creatine kinase and can precede or accompany acute kidney injury, depending on the severity and speed of the underlying process. The diagnosis rests on recognizing the clinical picture and distinguishing myoglobinuria from other causes of dark urine, such as true hematuria.

Although the underlying etiologies are diverse, myoglobinuria most often points to a rhabdomyolysis–related process. Rhabdomyolysis is a syndrome characterized by rapid breakdown of skeletal muscle, which releases intracellular contents into the bloodstream, including myoglobin, potassium, phosphate, and other intracellular enzymes. Causes range from traumatic injuries and crush injuries crush syndrome to prolonged immobilization, extreme physical exertion, seizures, temperature-related injuries (such as heat stroke), infections, and exposure to certain drugs or toxins. Drugs such as statins, illicit substances like cocaine, and other contributors can precipitate rhabdomyolysis in susceptible individuals. The broad clinical and etiologic spectrum of myoglobinuria means that clinicians must actively search for an inciting event while also treating the consequences of muscle breakdown.

Causes and pathophysiology

Causes

  • Trauma and crush injuries, including prolonged compression and compartment syndrome crush syndrome.
  • Prolonged immobilization or immobility-related rhabdomyolysis.
  • Extreme physical exertion, particularly in previously untrained individuals.
  • Seizures, electrocution, or other neurologic catastrophes leading to muscle damage.
  • Drugs and toxins, including statin-associated rhabdomyolysis, illicit substances such as cocaine, alcohol, and other metabolic toxins.
  • Metabolic and genetic myopathies, as well as conditions such as malignant hyperthermia that precipitate rapid muscle breakdown.
  • Infections and inflammatory myopathies that damage muscle tissue.

Pathophysiology

Muscle injury causes disruption of the sarcolemma and leakage of cytosolic contents into the circulation. The released myoglobin is filtered by the kidneys and can cause tubular obstruction and direct oxidative injury to tubular cells, contributing to acute kidney injury (AKI). The kidneys’ handling of myoglobin depends on urine flow, acid-base status, and perfusion; dehydration and aciduria amplify tubular toxicity. Systemic effects, such as hyperkalemia, hyperphosphatemia, hypocalcemia, and metabolic acidosis, reflect the release of intracellular constituents and can complicate management.

Diagnosis

Clinical features

  • Dark or cola-colored urine that persists after hydration status is addressed.
  • Muscle pain, tenderness, swelling, or weakness.
  • History pointing to a provoking event (trauma, exertion, toxin exposure) or a genetic/metabolic predisposition.

Laboratory findings

  • Marked elevation of creatine kinase in the blood, often exceeding several thousand units per liter.
  • Urinalysis may show a positive result on dipstick testing for blood due to the heme pigment, but microscopic examination reveals few if any red blood cells, helping distinguish myoglobinuria from true hematuria.
  • Elevated serum myoglobin can be detected with specialized assays, though CK elevation is a more widely available surrogate marker.
  • Renal function tests may show rising creatinine and urea, depending on the degree of AKI.
  • Electrolyte abnormalities, especially hyperkalemia, may accompany severe muscle injury.

Differential diagnosis

  • Hematuria from urinary tract pathology or glomerular disease.
  • Methemoglobinuria or other pigment-related causes of dark urine.
  • Other causes of AKI that may coexist with rhabdomyolysis.

Management

Initial management

  • Rapid assessment and stabilization of the patient, with attention to airway, breathing, and circulation as needed.
  • Aggressive isotonic intravenous fluid resuscitation (commonly normal saline) to maintain urine output and dilute filtered myoglobin, while monitoring intake and output.
  • Continuous monitoring of renal function and electrolytes, particularly potassium, phosphate, calcium, and bicarbonate.

Specific interventions

  • Urine alkalinization with bicarbonate has historically been used in some centers to reduce myoglobin precipitation in renal tubules; however, the evidence is mixed, and routine use is not universally recommended. Decisions about bicarbonate therapy should consider patient acid-base status and risk for complications.
  • Management of electrolyte disturbances, especially treating hyperkalemia promptly to prevent cardiac arrhythmias.
  • Avoidance of nephrotoxic agents, including certain drugs and contrast materials, where possible.
  • In cases of persistent oliguria or established AKI, renal replacement therapy (e.g., hemodialysis) may be required, particularly if there are severe electrolyte abnormalities, acidosis, or volume overload.

Cause-specific considerations

  • Treat the triggering condition (trauma, exertional injury, toxin exposure, or metabolic disease) to halt ongoing muscle damage and limit further myoglobin release.
  • In genetic or metabolic myopathies, long-term management involves disease-specific care and prevention strategies to reduce recurrence.

Prognosis and long-term considerations

With prompt recognition and appropriate management, many patients recover renal function and muscle strength. The risk of AKI is highest when myoglobin load, hypovolemia, and acidosis coincide, emphasizing the importance of early hydration and monitoring. Recurrent rhabdomyolysis may occur in certain metabolic or genetic disorders, necessitating lifestyle adjustments and ongoing medical supervision. Mortality is typically linked to the severity of the underlying muscle injury and the development of renal failure or serious electrolyte disturbances.

See also