Rhabdomyolysis — literally, the dissolution of striped (skeletal) muscle — is characterized by the leakage of muscle-cell contents, including electrolytes, myoglobin, and other sarcoplasmic proteins (e.g., creatine kinase, aldolase, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase) into the circulation.

Massive necrosis, which is manifested as limb weakness, myalgia, swelling, and, commonly, gross pigmenturia without hematuria, is the common denominator of both traumatic and nontraumatic rhabdomyolysis.^1,2

Acute kidney injury is a potential complication of severe rhabdomyolysis, regardless of whether the rhabdomyolysis is the result of trauma or some other cause, and the prognosis is substantially worse if renal failure develops.

In contrast, in less severe forms of rhabdomyolysis or in cases of chronic or intermittent muscle destruction — a condition sometimes called hyperCKemia — patients usually present with few symptoms and no renal failure.

We review the pathophysiological characteristics and management of acute kidney injury associated with rhabdomyolysis.

There are eight commonly reported categories of rhabdomyolysis (Table 1). Exogenous agents that can be toxic to muscles, especially alcohol, illicit drugs, and lipid-lowering agents, are common nontraumatic causes.

Recurrent episodes of rhabdomyolysis are often a sign of an underlying defect in muscle metabolism.^1,3,4

Acute rhabdomyolysis occasionally develops in patients with structural myopathies when they are performing strenuous exercise, are under anesthesia, have taken drugs that are toxic to muscles, or have viral infections.¹

When a diagnosis of acute rhabdomyolysis is suspected, histochemical, immunohistochemical, and mitochondrial respiration studies performed on a muscle-biopsy specimen may yield a specific diagnosis.

It is important to wait several weeks or months after the clinical event to perform a biopsy, because the results of a biopsy will typically be uninformative at an early stage.

Thus, the specimen may appear normal or show no specific findings other than necrosis during and early after the acute episode of rhabdomyolysis (Figure 1).^2,5
 
Figure 1. Histopathological Findings in Frozen Muscle-Tissue Specimens from Patients with Rhabdomyolysis.

Panel A shows massive muscle necrosis (arrows) in a patient with statin-related rhabdomyolysis (hematoxylin and eosin).

This histologic feature would be similar in every case of rhabdomyolysis, irrespective of the cause. Panel B shows the typical ragged-red fibers (arrows) in a muscle-biopsy specimen from a patient with mitochondrial myopathy that was obtained 3 months after an episode of severe rhabdomyolysis.

The mitochondrial dysfunction was confirmed by a mitochondrial respiratory chain–based assay (Gomori's trichrome). Panel C shows periodic acid–Schiff (PAS)–positive material (arrows) in some muscle fibers in a case of McArdle's disease.

The biopsy was performed a few months after the patient's recovery from recurrent rhabdomyolysis (PAS stain). Panel D shows a muscle-biopsy specimen from a patient with central core disease. The specimen was obtained after the patient's recovery from malignant hyperthermia.

Abundant central cores can be seen (arrows) (NADH–tetrazolium reductase stain). 

Figure 1. Histopathological Findings in Frozen Muscle-Tissue Specimens from Patients with Rhabdomyolysis.

Panel A shows massive muscle necrosis (arrows) in a patient with statin-related rhabdomyolysis (hematoxylin and eosin). This histologic feature would be similar in every case of rhabdomyolysis, irrespective of the cause. Panel B shows the typical ragged-red fibers (arrows) in a muscle-biopsy specimen from a patient with mitochondrial myopathy that was obtained 3 months after an episode of severe rhabdomyolysis. The mitochondrial dysfunction was confirmed by a mitochondrial respiratory chain–based assay (Gomori's trichrome). Panel C shows periodic acid–Schiff (PAS)–positive material (arrows) in some muscle fibers in a case of McArdle's disease. The biopsy was performed a few months after the patient's recovery from recurrent rhabdomyolysis (PAS stain). Panel D shows a muscle-biopsy specimen from a patient with central core disease. The specimen was obtained after the patient's recovery from malignant hyperthermia. Abundant central cores can be seen (arrows) (NADH–tetrazolium reductase stain).

 
The mechanisms involved in the pathogenesis of rhabdomyolysis are direct sarcolemmic injury (e.g., trauma) or depletion of ATP within the myocyte, leading to an unregulated increase in intracellular calcium.^6,7

Sarcoplasmic calcium is strictly regulated by a series of pumps, channels, and exchangers that maintain low levels of calcium when the muscle is at rest and allow the increase that is necessary for actin–myosin binding and muscle contraction.

Depletion of ATP impairs the function of these pumps, resulting in a persistent increase in sarcoplasmic calcium that leads to persistent contraction and energy depletion and the activation of calcium-dependent neutral proteases and phospholipases; the result is the eventual destruction of myofibrillar, cytoskeletal, and membrane proteins, followed by lysosomal digestion of fiber contents. Ultimately, the myofibrillar network breaks down, resulting in disintegration of the myocyte.² In the case of patients with rhabdomyolysis caused by trauma, additional injury results from ischemia reperfusion and inflammation by neutrophils that infiltrate damaged muscle.⁸

SEE FULLTEXT

NEJM Volume 361:62-72 July 2, 2009 Number 1

Xavier Bosch, M.D., Ph.D., Esteban Poch, M.D., Ph.D., and Josep M. Grau, M.D., Ph.D

http://content.nejm.org/cgi/content/full/361/1/62

http://www.e-medicum.com/noticiasDelDia/verNoticia.php?noticia=82892