What is the mechanism of myoglobinuria (presence of myoglobin in the urine)?

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From the Guidelines

Myoglobinuria occurs when myoglobin, a muscle protein, is released into the bloodstream following muscle damage and subsequently filtered by the kidneys into urine, leading to potential kidney damage and acute kidney injury. This process begins with muscle injury (rhabdomyolysis) caused by trauma, extreme exercise, medications, toxins, infections, or metabolic disorders 1. When muscle cells are damaged, their contents, including myoglobin, leak into the circulation. Myoglobin is toxic to kidneys through several mechanisms: it precipitates in acidic urine forming obstructive casts in renal tubules, releases free iron that generates harmful reactive oxygen species, causes vasoconstriction reducing renal blood flow, and directly damages tubular cells 1.

Key Mechanisms and Clinical Presentation

The kidneys attempt to filter this excess myoglobin, but when overwhelmed, acute kidney injury can develop. Clinically, myoglobinuria presents as tea or cola-colored urine, often accompanied by muscle pain, weakness, and swelling. The measurement of plasma myoglobin may be more sensitive and specific than CPKs in identifying the risk of acute kidney injury, which is correlated with increased mortality 1.

Treatment and Management

Treatment focuses on aggressive intravenous fluid administration to maintain urine output above 200 mL/hour, sometimes with sodium bicarbonate to alkalinize urine, preventing myoglobin precipitation and reducing kidney damage 1. The aim should be a urine output of > 2 ml.kg1.h1, and sodium bicarbonate is recommended to be used as it may help in preventing acute kidney injury from myoglobinuria 1. However, it's crucial to avoid potassium-containing balanced salt fluids and starch-based fluids, as they may worsen the condition 1. Severe cases may require dialysis if kidney function deteriorates significantly.

Considerations and Controversies

There is controversy regarding the administration of mannitol to disaster crush victims, as it has potential benefits but also requires close monitoring due to its nephrotoxic properties 1. The current evidence does not suggest a significant benefit from active alkalinization over active fluid resuscitation alone 1. Therefore, the management of myoglobinuria should prioritize aggressive fluid resuscitation and careful consideration of the patient's overall clinical condition.

From the Research

Mechanism of Myoglobinuria

  • Myoglobinuria occurs due to the breakdown of skeletal muscle cells, releasing myoglobin into the plasma and interstitial space 2, 3, 4, 5, 6.
  • The main pathophysiology of renal injury in myoglobinuria is due to vasoconstriction, intraluminal casts, tubular obstruction, and direct myoglobin toxicity 2.
  • Myoglobin has been identified as the primary muscle constituent contributing to renal damage in rhabdomyolysis 5.
  • The breakdown of skeletal muscle cells leads to the release of intracellular content, including myoglobin, into the bloodstream, which can cause acute kidney injury (AKI) 3, 4, 5, 6.

Causes of Myoglobinuria

  • Myoglobinuria can occur due to a variety of causes, including exertion, crush injury, trauma, alcoholism, drugs, and toxins 3, 4, 5.
  • Hereditary causes, such as disorders of carbohydrate metabolism, disorders of lipid metabolism, or diseases of the muscle associated with malignant hyperthermia, can also lead to myoglobinuria 4.
  • Prescription and over-the-counter medications, alcohol, and illicit drugs are common causes of rhabdomyolysis and subsequent myoglobinuria in hospitalized patients 5.

Clinical Presentation and Diagnosis

  • The clinical presentation of myoglobinuria can range from asymptomatic increases in serum levels of enzymes released from damaged muscles to severe conditions such as volume depletion, metabolic and electrolyte abnormalities, and AKI 3, 6.
  • The diagnosis of myoglobinuria is confirmed by elevated creatine kinase levels, and additional testing is needed to evaluate for potential causes, electrolyte abnormalities, and AKI 3, 5, 6.
  • Myoglobinuria can be diagnosed by urinalysis, which checks for the presence of myoglobin in the urine 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Rhabdomyolysis.

Disease-a-month : DM, 2020

Research

[Rhabdomyolysis and myoglobinuria].

Der Nervenarzt, 2003

Research

Rhabdomyolysis.

Chest, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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