What causes and how to manage acute kidney injury (AKI) due to rhabdomyolysis?

From the Guidelines

Rhabdomyolysis causes a type of acute kidney injury (AKI) characterized by renal tubular obstruction, direct toxicity, and vasoconstriction, resulting from the release of myoglobin into circulation. The management of AKI due to rhabdomyolysis involves aggressive fluid resuscitation with isotonic saline, monitoring of serum creatinine, electrolytes, creatine kinase levels, and urine output, as well as prevention of compartment syndrome through monitoring of affected limbs 1. Key aspects of management include:

• Aggressive fluid resuscitation with isotonic saline, starting at 10-15 mL/kg/hour initially, and adjusting based on clinical response, targeting urine output of 200-300 mL/hour until myoglobinuria resolves
• Monitoring of serum creatinine, electrolytes (especially potassium, calcium, and phosphate), creatine kinase levels, and urine output
• Prevention of compartment syndrome through monitoring of affected limbs, which is crucial in patients with severe limb trauma 1
• Early nephrology consultation is recommended for patients with significant AKI, oliguria despite fluid resuscitation, or severe electrolyte disturbances Common causes of rhabdomyolysis-induced AKI include trauma, extreme exertion, medications (statins, colchicine), illicit drugs, infections, and prolonged immobility 1. Severe cases may require renal replacement therapy, especially with persistent hyperkalemia, acidosis, or uremia. The use of sodium bicarbonate to alkalinize urine is no longer routinely recommended, and mannitol is also not recommended for routine use in rhabdomyolysis-induced AKI 1. Overall, the goal of management is to prevent further kidney damage, manage electrolyte imbalances, and support renal function until recovery.

From the FDA Drug Label

Renal complications, including irreversible renal failure have been reported in patients receiving mannitol. Reversible, oliguric acute kidney injury (AKI) has occurred in patients with normal pretreatment renal function who received mannitol

The type of AKI caused by rhabdomyolysis is not directly addressed in the provided drug labels. However, it can be inferred that rhabdomyolysis may lead to prerenal AKI due to hypovolemia, or intrarenal AKI due to myoglobinuria and direct tubular injury.

• Prerenal AKI is caused by decreased blood flow to the kidneys, which can occur due to hypovolemia or dehydration.
• Intrarenal AKI is caused by direct injury to the kidney tissues, which can occur due to myoglobinuria or other toxins. Management of AKI due to rhabdomyolysis typically involves:
• Aggressive fluid resuscitation to correct hypovolemia and maintain urine output.
• Monitoring of renal function and electrolyte levels.
• Avoidance of nephrotoxic agents.
• Consideration of other treatments, such as alkalinization of the urine or use of mannitol, although the provided drug labels do not directly support the use of mannitol for this indication 2, 2.

From the Research

Causes of Acute Kidney Injury (AKI) due to Rhabdomyolysis

• Rhabdomyolysis is a clinical syndrome characterized by the breakdown of skeletal muscle cells and release of creatine kinase (CK), lactate dehydrogenase (LDH), and myoglobin into the plasma and interstitial space 3.
• The main pathophysiology of renal injury is due to vasoconstriction, intraluminal casts, tubular obstruction, and direct myoglobin toxicity 3, 4.
• Rhabdomyolysis can occur due to a variety of causes, including direct muscular injury, strenuous exercise, drugs, toxins, infections, hyperthermia, seizures, metabolic and/or electrolyte abnormalities, and endocrinopathies 4.

Management of AKI due to Rhabdomyolysis

• Early diagnosis and prompt management with fluid resuscitation, initiation of renal replacement therapy (RRT), and elimination of causative agents can help prevent complications 3.
• Electrolyte disturbances should always be detected in the early stages and carefully treated 5.
• The use of bicarbonates or diuretics may also be helpful, but especially in the latter case, the indications should be well evaluated, remembering to avoid hypovolemia 5.
• Limited use of bicarbonate and adjustment of fluid volume may improve the short- and long-term outcomes of patients with rhabdomyolysis 6.
• Saline volume expansion may reduce the risk of AKI 4.

Diagnosis of Rhabdomyolysis-Induced AKI

• Serum CK five times higher than the normal value usually confirms rhabdomyolysis 4.
• However, CPK alone may not be a sensitive marker for rhabdomyolysis-induced AKI in some cases, and other diagnostic markers such as myoglobin casts may be necessary 7.
• Urinalysis and kidney biopsy may also be helpful in diagnosing rhabdomyolysis-induced AKI 7.