Rhabdomyolysis: Revisited

Abstract

Rhabdomyolysis (RML) is a pathological entity characterized by symptoms of myalgia, weakness and dark urine (which is often not present) resulting in respiratory failure and altered mental status. Laboratory testing for myoglobinuria is pathognomonic but so often not present during the time of testing that serum creatine kinase should always be sent when the diagnosis is suspected. Kidney injury from RML progresses through multiform pathways resulting in acute tubular necrosis. Early treatment (ideally<6 hoursfrom onset) is needed with volume expansion of all non-overloaded patients along with avoidance of nephrotoxins. There is insufficient data to recommend any specific fluid. The mortality rate ranges from 10% to up to 50% with severe AKI, so high index of suspicion and screening should be in care plan of seriously ill patients at risk for RML.

Keywords: Rhabdomyolysis; acute kidney injury; pathophysiology; treatment.

Figure 1

Causes of rhabdomyolysis

Figure 2

Injury mechanisms of rhabdomyolysis. Energy (ATP) depletion inhibits Na⁺/K⁺ ATPase function, thus increasing intracellular sodium. The 2Na⁺/Ca2⁺ exchanger increases intracellular calcium. Ca2⁺ ATPase is not able to pump out intracellular calcium due to energy depletion. Intracellular calcium activates proteases such as phospholipase 2 (PLA2), which destroy structural components of the cell membrane, allowing the entrance of more calcium. Calcium overload disrupts mitochondrial integrity and induces apoptosis leading to muscle cell necrosis. (Adapted from Chavez et al: Beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice. Crit Care Lond Engl. 2016 Jun 15;20(1):135. Open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).

Figure 3

Pathophysiology of rhabdomyolysis-induced acute kidney injury. CO, carbon monoxide; EC, extracellular; Fe 2+ , ferrous iron; Fe 3+, ferric iron; Fe4 = O, ferryl iron; HO-1, heme oxygenase-1; H2O2, hydrogen peroxide; MB, myoglobin; MC, muscle cell; MT, mitochondria; NO, nitric oxide; OH-, hydroxyl anion; O2-, superoxide radical; OH*, hydroxyl radical, RAAS, renin-angiotensin-aldosterone system; RBF, renal blood flow; ROS, reactive oxygen species; SOD, superoxide dismutase; TC, tubular cell. (Adapted from: Petejova et al : Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review. Crit Care Lond Engl. 2014 May 28;18(3):224. Open access article distributed under the terms of the Creative Commons Attribution License. (http://creativecommons.org/licenses/by/2.0)32

Figure 4

Time course (in hours; y-axis) of serum myoglobin, CK, and creatinine with respect to the insult. CK, creatine kinase.

Figure 5

Kidney biopsy showing positive immunoperoxidase staining for myoglobin pigmented casts in a young female with heavy cocaine use and acute kidney injury. (Modified from Mansoor et al : Systematic review of nephrotoxicity of drugs of abuse, 2005-2016. BMC Nephrol [Internet]. 2017 Dec 29 [cited 2020 Apr 30];18. Open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).64