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Year : 2021  |  Volume : 64  |  Issue : 2  |  Page : 382-384
Rhabdomyolysis with myoglobin-induced acute kidney injury: A case series of four cases

1 Department of Nephrology, Government Kilpauk Medical College, Chennai, Tamil Nadu, India
2 Renopath, Center for Renal and Urological Pathology, Chennai, Tamil Nadu, India

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Date of Submission20-Feb-2020
Date of Decision08-Apr-2020
Date of Acceptance18-May-2020
Date of Web Publication9-Apr-2021


Rhabdomyolysis is a potentially life-threatening 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. Rhabdomyolysis can occur due to a variety of causes and acute kidney injury (AKI) is one of its most dreaded complications occurring in 33%–50% patients. The main pathophysiology of renal injury is due to vasoconstriction, intraluminal casts, tubular obstruction, and direct myoglobin toxicity. As the symptoms are nonspecific, a high level of suspicion is required in the mind of the treating physician. Early diagnosis and prompt management with fluid resuscitation, initiation of renal replacement therapy (RRT), and elimination of causative agents can help prevent complications. We hereby report four interesting cases of this clinical syndrome with emphasis on the causative agents.

Keywords: Creatine kinase, myoglobin, rhabdomyolysis

How to cite this article:
Samuel HU, Balasubramaniyan T, Thirumavalavan S, Vasudevan C, Senthil Kumar R P, Murugesan V, Abraham A. Rhabdomyolysis with myoglobin-induced acute kidney injury: A case series of four cases. Indian J Pathol Microbiol 2021;64:382-4

How to cite this URL:
Samuel HU, Balasubramaniyan T, Thirumavalavan S, Vasudevan C, Senthil Kumar R P, Murugesan V, Abraham A. Rhabdomyolysis with myoglobin-induced acute kidney injury: A case series of four cases. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 May 8];64:382-4. Available from: https://www.ijpmonline.org/text.asp?2021/64/2/382/313304

   Introduction Top

Rhabdomyolysis is characterized by necrosis of muscle cells and the release of intracellular contents into blood. One of the key compounds released is myoglobin, a 17,800D oxygen carrier.[1] Approximately 33%–50% of patients with rhabdomyolysis develop acute kidney injury (AKI).[2] Rhabdomyolysis is characterized by myoglobinuria and elevated muscle enzymes including creatine kinase (CK) in the blood. Higher levels of CK increase the risk of AKI in patients with rhabdomyolysis. Concentrations of CK >5000 U/L are associated with an incidence of AKI >50%.[3] Small quantities of myoglobin present in plasma are normally loosely bound to plasma globulins and do not cross the glomerulus. However if large quantities of myoglobin are released, this transport system is overwhelmed and myoglobin is easily filtered through the glomerular basement membrane entering the renal tubules. Myoglobin-induced AKI occurs due to tubular obstruction, renal vasoconstriction, and tubular damage by oxidative injury.[4] The prognosis for myoglobin-induced AKI is excellent and full renal recovery is expected within 3 months in the majority of cases. We describe four cases of rhabdomyolysis with myoglobin-induced AKI and demonstration of myoglobin casts in renal biopsy.

   Case Report Top

Four cases of rhabdomyolyis with myoglobin-induced AKI caused by varying etiologies were encountered in our institution. The causes included snake bite, drugs-haloperidol and benzodiazepine, high-dose rosuvastatin, and multiple substance abuse-cannabis and MDMA (methylenedioxy-methamphetamine). The demographic details and management are summarized in [Table 1].
Table 1: Causes, clinical parameters, management, and outcome of patients

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The clinical presentations were varied and nonspecific in all cases. CK was elevated in all cases––highest with multiple substance abuse (26,600 U/L) and lowest with high-dose rosuvastatin intake (5162 U/L). Serum creatinine was elevated in all cases––highest with antipsychotic intake (17.8 mg/dL) and lowest with snake bite (4 mg/dL). Renal biopsy of all cases showed features of tubular epithelial cell injury with pigment casts in tubules. Many of the tubular epithelial cells were swollen and showed cytoplasmic vacuoles and loss of brush borders. Some of the epithelial cells were sloughed off and others were attenuated. Reddish-brown granular bead-like casts were seen in some of the tubules [Figure 1]a. Immunohistochemical stain for myoglobin was positive over the tubular casts in all four cases [Figure 1]b. All patients required hemodialysis with an average of 9.5 sessions per patient. One patient with statin-induced AKI ended in CKD-nondialysis requiring due to underlying diabetic nephropathy, whereas other patients had excellent renal recovery. Comorbidities were found to complicate rhabdomyolysis-induced AKI.
Figure 1: (a) ATI with dilated tubules, thinned out tubular epithelial cells, and intratubular casts (H&E, 100x). (b) IHC intensely positive for myoglobin (IHC, 200×)

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   Discussion Top

The term "rhabdomyolysis" refers to the disintegration of striated muscle resulting in the release of cell constituents into extracellular fluid and circulation. One of the key compounds released is myoglobin which resembles hemoglobin, but contains only one heme moiety. Normally myoglobin is loosely bound to plasma globulins and only small amounts reach the urine. When massive amounts of myoglobin are released, the binding capacity of plasma protein is exceeded. Myoglobin is then filtered by glomeruli and reaches the tubules, where it may cause an obstruction and renal dysfunction.[5] The causes of rhabdomyolysis include trauma, increased muscle activity, exogenous toxins or medications, hereditary myopathy, myositis, hypokalemia, hypophosphatemia, or hyperosmolarity.[6]

Myoglobinuria does not occur without rhabdomyolysis, but rhabdomyolysis does not necessarily result in visible myoglobinuria. Myoglobin causes discoloration of urine but not of plasma. Urinary myoglobin provokes a typical reddish-brown color, even in the absence of hematuria.[7] Myoglobin is rapidly eliminated by hepatic metabolism; therefore, tests for myoglobin in plasma or urine are not sensitive diagnostic procedures. Elevated serum CK levels are enough to establish the diagnosis of rhabdomyolysis. A five times higher than the normal value of CK confirms the diagnosis of rhabdomyolysis.[8] Myoglobin is filtered freely by the glomeruli and concentrated intratubular myoglobin in the presence of acidic urine precipitates with Tamm–Horsfall protein to form intratubular casts obstructing the renal tubules. Although heme pigment resulting from myoglobin degradation has a direct tubulotoxic effect, other precipitating factors such as volume depletion, acidosis, and ischemia are usually needed for myoglobinuria to induce AKI. Ferrihemate, a degradation product of heme, is more tubulotoxic. Through inhibition of nitric oxide synthase, ferrihemate leads to vasoconstriction.

In light microscopy, there are features of acute tubular injury (ATI) with attenuation of tubular epithelial cells, cytoplasmic vacuoles, brush border loss and intratubular sloughed epithelial cells, and cell debris. Myoglobin casts are composed of round granules in chains or aggregate in clusters. The granules may have fine granular or a coarse beaded appearance. Their color ranges from pink to red-brown with hematoxylin and eosin stain (H&E), light brown to black with jones methenamine silver stain, pink to bright magenta with periodic acid–Schiff stain, and bright red with trichrome stain.[9] The histopathological differential diagnosis includes hemolysis associated with hemoglobin casts, which have the same appearance on routine light microscopy. There are no morphological characteristics to differentiate myoglobin casts from hemoglobin casts. Therefore, immunohistochemical staining is required to confirm the diagnosis.[10]

Early diagnosis and volume expansion usually reduce the risk of AKI. Most patients recover renal function if the underlying cause is treated although RRT may be needed. Myoglobin, because of its size, is poorly removed by either hemofiltration or peritoneal dialysis. There are no data indicating a role for extracorporeal methods such as plasmapheresis. The prognosis is excellent and full renal recovery is expected within 3 months in the majority of cases. We highlight the need for suspecting and evaluating myoglobin-induced AKI for rare and varied nontraumatic causes through this case series.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Kagen LJ. Serum myoglobin. Arch Inter Med 1979;139:628-9.  Back to cited text no. 1
Zager RA. Studies of mechanisms and protective manoeuvres in myoglobinuric acute renal injury. Lab Invest 1989;60:619-29.  Back to cited text no. 2
Hunter JD, Gregg K, Damani Z. Rhabdomyolysis. Contin Educ Anaesth Crit Care Pain 2006;6:141-3.  Back to cited text no. 3
Holt S, Moore K. Pathogenesis of renal failure in rhabdomyolysis: The role of myoglobin. Nephron Exp Nephrol 2000;8:72-6.  Back to cited text no. 4
Zager RA. Rhabdomyolysis and myohemoglobinuric acute renal failure. Kidney Inter 1996;49:314-26.  Back to cited text no. 5
Najafian B, Fogo AB, Lusco MA, Alpers CE. Atlas of renal pathology: Myoglobin cast nephropathy. Am J Kidney Dis 2017;69:7-8.  Back to cited text no. 6
Van holder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol 2000;11:1553-61.  Back to cited text no. 7
Torres, Kimura E, Mosqueda JL, Garcia, Dominguez, Herrera MF. Pressure-induced rhabdomyolysis after bariatric surgery. Obes Surg 2003;13:297-301.  Back to cited text no. 8
Liapis H, Boils C, Hennigar R, Silva F. Myoglobin casts in renal biopsies: Immunohistochemistry and morphologic spectrum. Hum Pathol 2016;54:25-30.  Back to cited text no. 9
Dvanajscak Z, Walker PD, Cossey LN, Messias NC, Boils CL, Kuperman MB, et al. Haemolysis-associated haemoglobin cast nephropathy results from a range of clinicopathologic disorders. Kidney Inter 2019;96:1400-7.  Back to cited text no. 10

Correspondence Address:
Hanock Unni Samuel
Department of Nephrology, Government Kilpauk Medical College, Kilpauk, Chennai, Tamil Nadu-600 010
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_89_20

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