Rhabdomyolysis is a common condition which is often missed out. This article not only focuses on etiopathogenesis but also on evaluation and treatment.

Rhabdomyolysis

Rhabdomyolysis is a condition marked by the breakdown of skeletal muscle tissue, leading to the release of various muscle cell components like electrolytes, myoglobin, and enzymes into the bloodstream. This process can occur due to trauma or other causes and is characterised by symptoms such as limb weakness, muscle pain, swelling, and dark urine.

Aetiology

1. Trauma: Crush syndrome resulting from physical injury.
2. Exertion: Strenuous exercise, seizures, and alcohol withdrawal syndrome.
3. Muscle hypoxia: Limb compression during prolonged immobilisation or loss of consciousness, major artery occlusion.
4. Genetic defects: Disorders affecting glycolysis or glycogenolysis, including various types of glycogenosis and disorders of lipid metabolism.
5. Mitochondrial disorders: Conditions affecting succinate dehydrogenase, cytochrome c oxidase, coenzyme Q10, and others.
6. Infections: Viral infections like influenza A and B, coxsackievirus, Epstein–Barr virus, primary human immunodeficiency virus, and legionella species, as well as bacterial infections like Streptococcus pyogenes, Staphylococcus aureus (pyomyositis), clostridium.
7. Body temperature changes: Heat stroke, malignant hyperthermia, malignant neuroleptic syndrome, hypothermia.
8. Metabolic and electrolyte disorders: Conditions such as hypokalemia, hypophosphatemia, hypocalcemia, nonketotic hyperosmotic conditions, and diabetic ketoacidosis.
9. Drugs and toxins: Including lipid-lowering drugs (fibrates, statins), alcohol, heroin, and cocaine.
10. Idiopathic: Cases of unknown or sometimes recurrent causes.

These categories encompass a wide range of potential triggers for rhabdomyolysis, highlighting the diverse nature of this condition.

Pathogenesis

The pathogenesis of myoglobin-induced acute kidney injury (AKI) in the context of rhabdomyolysis involves several key mechanisms:

1. Myoglobinuria: Myoglobin, a protein released from damaged muscle cells, enters the tubule epithelial cells through endocytosis. It becomes visible in urine when serum levels exceed a certain threshold and can lead to reddish-brown ("tea-coloured") urine.
2. Intrarenal vasoconstriction, direct and ischemic tubule injury, and tubular obstruction all contribute to impairing the glomerular filtration rate. Myoglobin concentrates along the renal tubules, particularly enhanced by volume depletion and renal vasoconstriction.
3. Nephrotoxicity: Myoglobin is a heme protein containing iron, which can generate hydroxyl radicals, leading to oxidative stress and cellular injury.

These mechanisms collectively result in the impairment of renal function and contribute to the development of AKI in rhabdomyolysis-induced renal injury.

Approach and evaluation

1. Clinical presentation: Patients with acute rhabdomyolysis typically present with pigmented granular casts, reddish-brown urine, and significantly elevated serum creatine kinase levels. However, there's no specific threshold value of serum creatine kinase above which the risk of acute kidney injury (AKI) is markedly increased.
2. Creatine kinase levels and AKI risk: While the correlation between peak creatine kinase levels and the incidence of AKI is weak, the risk of developing AKI is generally low when creatine kinase levels at admission are below 15,000 to 20,000 u/l.
3. Myoglobinuria: Myoglobin, the pathogenic factor in rhabdomyolysis-induced AKI, can be inferred from urinary dipstick testing.
4. Serum myoglobin levels: Measurement of serum myoglobin has low sensitivity for diagnosing rhabdomyolysis.
5. Renal function changes: AKI associated with rhabdomyolysis often leads to a rapid increase in plasma creatinine, and oliguria or anuria may occur. A low fractional excretion of sodium (<1%) is characteristic, reflecting preglomerular vasoconstriction and tubular occlusion.
6. Electrolyte abnormalities: Electrolyte abnormalities accompanying rhabdomyolysis include hyperkalemia, hyperphosphatemia, hyperuricemia, high anion-gap metabolic acidosis, and hypermagnesemia, especially in the presence of renal failure. These abnormalities can precede AKI and should be measured early in diagnosis.

Management

Treatment and prevention strategies for rhabdomyolysis-induced acute kidney injury involve several key interventions:

1. Fluid repletion: Early and aggressive repletion of fluids is crucial, with patients often requiring around 10 litres of fluid per day. The amount administered depends on the severity of rhabdomyolysis. Prompt initiation of fluid therapy is essential for better outcomes.
2. Fluid composition: The choice of fluid composition for repletion is controversial. Some advocate for sodium bicarbonate to alkalinise urine, while others prefer normal saline. Alkalinisation may prevent myoglobin precipitation and reduce tubule injury but can also exacerbate hypocalcemia. Combining normal saline with sodium bicarbonate is a reasonable approach, especially in cases of metabolic acidosis.
3. Diuretics: Loop diuretics may be used to increase urinary flow and decrease the risk of myoglobin precipitation. However, their benefit in rhabdomyolysis-induced acute kidney injury is uncertain and should be restricted to patients with adequate fluid repletion.
4. Electrolyte abnormalities: Prompt correction of electrolyte abnormalities, especially hyperkalemia, is crucial. Agents that shift potassium into cells, such as insulin and glucose or β2-adrenergic agonists, can be administered. Calcium supplementation should be considered for hypocalcemia.
5. Renal-replacement therapy: Severe cases of acute kidney injury may necessitate renal-replacement therapy, primarily intermittent hemodialysis, to correct electrolyte imbalances rapidly and efficiently. Continuous venovenous hemofiltration or hemodiafiltration may be considered for myoglobin removal but lacks conclusive evidence of efficacy.
6. Antioxidants and free-radical scavengers: While antioxidants and free-radical scavengers have been studied, their role in preventing or treating rhabdomyolysis-induced acute kidney injury remains uncertain.
7. Monitoring and follow-up: Regular monitoring of electrolytes, fluid balance, and renal function is essential throughout treatment. Adjustments to therapy should be made based on clinical response and laboratory findings.
8. Calcium metabolism: Hypocalcemia is common due to calcium entering ischemic and damaged muscle cells and precipitation of calcium phosphate. However, hypercalcemia can occur during recovery, resulting from the mobilisation of calcium previously deposited in muscle, normalisation of hyperphosphatemia, and an increase in calcitriol.

Case study

Patient background: A 34-year-old male patient went on a religious trip and walked barefoot in sunlight for 40 km in 3-4 days.

Initial symptoms: Following that he started developing muscle weakness for which he took NSAIDS and body massage, but his condition worsened and he developed oliguria and breathlessness.

Medical evaluation: On evaluation, he had severe AKI with metabolic acidosis and volume overload.

Treatment: He needed hemodialysis on alternate days for 2-3 weeks.

Recovery: After that spontaneously he started improving with increasing urine output. After 6-8 weeks of supportive therapy, his renal function was normal with normal muscle power.

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Bhavin Mandowara is a practising nephrologist at Zydus Hospital, Ahmedabad.