Rhabdomyolysis As a Cause of Acute Kidney Injury

For some reason, the college loves rhabdomyolysis. Many questions either ask about it directly, or expect it as one of the differentials. Typically, the candidate is presented with a biochemistry panel strongly suspicious of rhabdomyolysis (eg. raised CK, LDH, potassium) as well as a history suggestive of some sort of crush injury or limb ischaemia. They are then asked to explain the mechanism, list the features, and describe their management.

Previous SAQs on this topic include the following:

Causes of rhabdomyolysis

A nice NEJM article has within it a comprehensive table (Table 1).

It has been rearranged into a familiar framework:

Causes of Rhabdomyolysis

Vascular causes

  • Embolic phenomena
  • Vascular insufficiency

Infectious causes

  • S.pyogenes or C.perfringens infections
  • Necrotising fasciitis

Neoplastic causes

  • Paraneoplastic cause of autoimmune myositis

Drug-related causes

  • Antipsychotics (neuroleptic-malignant syndrome)
  • SSRIs (serotonin syndrome)
  • Statins
  • Alcohol
  • Cocaine
  • MDMA
  • Volatile anaesthetics (malignant hyperthermia)
  • Propofol infusion syndrome
  • Imatinib, sunatinib (tyrosine kinase inhibitors)
  • Daptomycin (Hohenegger, 2012)

Idiopathic causes

  • Extreme exertion, eg. strenuous exercise
  • Seizures

Congenital causes

  • Congenital abnormalities of glycogenesis, lipid metabolism, mitochondrial disorders, and G6PD deficiency

Autoimmune causes

  • Myositis and dermatomyositis

Traumatic causes

  • Crush injury
  • Prolonged immobilisation, eg. for prolonged surgery as in Question 5 from the first paper of 2017
  • Heat stroke
  • Compartment syndrome
  • Trauma to arteries supplying the extremities

Endocrine causes

  • HONK
  • DKA
  • Hypokalemia

Mechanisms of kidney injury in rhabdomyolysis

In brief summary, these are the cardinal pathophysiological events in rhabdomyolysis:

  • Tubular obstruction by precipitating myoglobin
  • Free-radical-mediated injury due to generation of hydroxyl radicals by Fe2+
  • Lipid peroxidation by hydroxyl radicals and directly by haem, leading to tubular membrane dysfunction and sloughing
  • Renal vasoconstriction - possibly due to nitric oxide scavenging by myoglobin
  • Decreased renal blood flow due to shock in trauma

This has been asked about in Question 30 from the second paper of 2014. The multiple mechanisms which lead to acute kidney injury in rhabdomyolysis are well described in this excellent article. It would probably be counterproductive to digress extensively on this minor topic in this summary.

Manifestations of rhabdomyolysis

This has been examined in Question 16 from the first paper of 2008.

  • Historical features: Trauma, seizures, immobility, drug exposure
  • Symptoms:- muscle pain, decreased mobility, weakness, tea-coloured urine
  • Signs: Muscle compartment swelling, tenderness, weakness, fever
  • Biochemistry: Elevated CK, AST, LDH, urinary myoglobin; renal dysfunction and electrolyte abnormalities (particularly hyperkalemia, hypocalcemia, hyperphosphataemia, hyperuricemia, lactic acidosis). DIC may also result.
  • Imaging: CT or MRI evidence of muscle oedema; ultrasound evidence of decreased compartment perfusion.

Management of rhabdomyolysis

A recent meta-analysis of management strategies for rhabdomyolysis has presented the following conclusions:

  • Commence IV fluids within 6 hours - as early as possible
  • Aim for a urine output greater than 300ml/hr
  • Use of sodium bicarbonate is only indicated to correct systemic acidosis. There is no evidence for any benefit in rhabdomyolysis-induced AKI except for some uncontrolled case series, which does not stop people from recommending it anyway. It appears in the 2010 college answer, which pre-dates the 2013 meta-analysis. The savvy trainee seeking to remain in the good books with examiners who use forced alkaline diuresis will want to mention this therapy in their answer, with the caveat that it is may not be helpful, but is also probably not harmful.
  • Use of mannitol is only indicated if urine output >300ml/hr cannot be maintained

Dialysis may be commenced to improve the removal of myoglobin, if a high-permeability membrane filter is available. Even if it is not, standard CVVHDF seems to decrease the risk of renal injury.

 

References

The best shortcut for the time-poor exam candidate is this UpToDate article.

Bosch, Xavier, Esteban Poch, and Josep M. Grau. "Rhabdomyolysis and acute kidney injury." New England Journal of Medicine 361.1 (2009): 62-72.

Shapiro, Mark L., Anthony Baldea, and Fred A. Luchette. "Rhabdomyolysis in the intensive care unit." Journal of intensive care medicine 27.6 (2012): 335-342.

Holt, S., and K. Moore. "Pathogenesis and treatment of renal dysfunction in rhabdomyolysis." Intensive care medicine 27.5 (2001): 803-811.

Vanholder, Raymond, et al. "Rhabdomyolysis." Journal of the American Society of Nephrology 11.8 (2000): 1553-1561.

Bosch, Xavier, Esteban Poch, and Josep M. Grau. "Rhabdomyolysis and acute kidney injury." New England Journal of Medicine 361.1 (2009): 62-72.

Allison, Ronald C., and D. Lawrence Bedsole. "The other medical causes of rhabdomyolysis." The American journal of the medical sciences 326.2 (2003): 79-88.

Brown, Carlos VR, et al. "Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference?." Journal of Trauma-Injury, Infection, and Critical Care 56.6 (2004): 1191-1196.

Scharman, Elizabeth J., and William G. Troutman. "Prevention of kidney injury following rhabdomyolysis: a systematic review." Annals of Pharmacotherapy47.1 (2013): 90-105.

Sorrentino, Sajoscha A., et al. "High permeability dialysis membrane allows effective removal of myoglobin in acute kidney injury resulting from rhabdomyolysis." Critical care medicine 39.1 (2011): 184-186.

Tang, Wanxin, et al. "Renal protective effects of early continuous venovenous hemofiltration in rhabdomyolysis: improved renal mitochondrial dysfunction and inhibited apoptosis." Artificial organs 37.4 (2013): 390-400.

Ioannidis, Konstantinos, et al. "Safety and effectiveness of the combination acetazolamide and bicarbonates to induce alkaline diuresis in patients with rhabdomyolysis." European Journal of Hospital Pharmacy 22.6 (2015): 328-332.

Hohenegger, Martin. "Drug induced rhabdomyolysis." Current opinion in pharmacology 12.3 (2012): 335-339.