eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Myoglobinuria: Differential Diagnoses & Workup

Author: Prasad Devarajan, MD, Louise M Williams Endowed Chair in Pediatrics, Professor of Pediatrics and Developmental Biology, Director of Nephrology and Hypertension, Director of Clinical Nephrology Laboratories, Chief Executive Officer of Dialysis Unit, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine
Coauthor(s): Watson C Arnold, MD, Director, Department of Pediatric Nephrology, Cook Children's Medical Center
Contributor Information and Disclosures

Updated: Jul 27, 2009

Differential Diagnoses

Acidosis, Metabolic
Hypokalemia
Asthma
Hyponatremia
Bacteremia
Mixed Connective Tissue Disease
Birth Trauma
Parainfluenza Virus Infections
Child Abuse & Neglect: Physical Abuse
Rhabdomyolysis
Dehydration
Status Epilepticus
Down Syndrome
Tumor Lysis Syndrome
Head Trauma
Viral Hemorrhagic Fevers
Hypercalcemia
Hyperthyroidism
Hypocalcemia

Other Problems to Be Considered

Metabolic myopathies
Sepsis

Workup

Laboratory Studies

  • The most important laboratory test is measurement of creatine kinase (CK) levels to assess for rhabdomyolysis.
    • Myoglobin is the first enzyme that increases, but it returns to normal levels within the first 24 hours after the onset of symptoms. This is because myoglobin is rapidly cleared from the serum into the urine. However, serum CK levels may remain elevated after serum and urine test results for myoglobin have become negative. Serum CK levels typically peak about 3 days after the onset of symptoms, and remain elevated for several days. Thus, although the detection of myoglobin in the serum is considered pathognomonic for rhabdomyolysis, the serum CK level is a more useful marker for the diagnosis and assessment of severity because of its delayed clearance from the plasma.
    • Levels of other muscle enzymes, such as aldolase, LDH, or serum glutamic-oxaloacetic transaminase (SGOT), may also be elevated.
  • Electrolyte abnormalities may cause or result from rhabdomyolysis, including hyperkalemia and hyperphosphatemia from the damaged muscle cells.
    • Hypocalcemia may develop from the hyperphosphatemia or as result of calcium deposition in the damaged muscles.
    • Uric acid values may be elevated, and metabolic acidosis may develop.
  • Acute renal insufficiency (elevated BUN and creatinine levels) is a consequence of severe myoglobinuria in which the globulin precipitates and blocks the urinary tubules.
    • Creatinine levels may be elevated out of proportion to BUN levels.
    • Alkalinization of the urine and increased urine flow facilitates myoglobin excretion.
  • Although both myoglobinuria and hemoglobinuria may cause a tea-colored appearance of the urine, and although both cause positive results on the urine dipstick for blood, myoglobinuria may be differentiated from hemoglobinuria by performing a series of simple tests.
    • Myoglobinuria is brown, and often only a few RBCs are present in the urine.
    • Hematuria produces a reddish sediment in spun urine samples.
    • Red or brown urine with a negative dipstick result for blood indicates a dye in the urine.
    • Hemoglobin produces a reddish or brown coloration in the spun serum, whereas myoglobin does not discolor the serum.
    • CK levels are markedly elevated in myoglobinuria.
    • Results of radioimmunoassays for the specific measurement of serum or urine myoglobin can be delayed by several days and are not useful in immediate diagnosis and treatment.
  • Other electrolytic abnormalities associated with rhabdomyolysis result from the extrusion of intracellular contents into the plasma and include hyperkalemia, hypercalcemia or hypocalcemia, hyperphosphatemia, and hyperuricemia.

Imaging Studies

  • Imaging studies are rarely of use in this metabolic disorder.
  • Intravenous (IV) pyelograms may reveal a dense renogram, but most are normal.

Other Tests

  • Tests for sickle cell disease (eg, sickle preparations, hemoglobin electrophoresis) may reveal patients who are prone to rhabdomyolysis.
  • A drug and metabolic screen of the urine, blood, or both may indicate illicit drug use.
  • Complements and antinuclear antibodies may help in differentiating autoimmune polymyositis from other conditions.
  • In patients with acute renal insufficiency due to myoglobinuria, fractional excretion of sodium (FENa) is less than 1%, probably because tubular obstruction and damage is the cause of oliguria rather than glomerular damage.

Procedures

  • Muscle biopsy may be of use when a metabolic myopathy is suspected.

More on Myoglobinuria

Overview: Myoglobinuria
Differential Diagnoses & Workup: Myoglobinuria
Treatment & Medication: Myoglobinuria
Follow-up: Myoglobinuria
Multimedia: Myoglobinuria
References

References

  1. [Guideline] Clarke W, Frost SJ, Kraus E, et al. Renal function testing. Laboratory medicine practice guidelines: evidence-based practice for point-of-care testing. National Academy of Clinical Biochemistry (NACB). 2006;[Full Text].

  2. Fernandez WG, Hung O, Bruno GR, Galea S, Chiang WK. Factors predictive of acute renal failure and need for hemodialysis among ED patients with rhabdomyolysis. Am J Emerg Med. Jan 2005;23(1):1-7. [Medline].

  3. Mannix R, Tan ML, Wright R, Baskin M. Acute pediatric rhabdomyolysis: causes and rates of renal failure. Pediatrics. Nov 2006;118(5):2119-25. [Medline].

  4. Dalakas MC. Toxic and drug-induced myopathies. J Neurol Neurosurg Psychiatry. Aug 2009;80(8):832-8. [Medline].

  5. Coco TJ, Klasner AE. Drug-induced rhabdomyolysis. Curr Opin Pediatr. Apr 2004;16(2):206-10. [Medline].

  6. Huerta-Alardin AL, Varon J, Marik PE. Bench-to-bedside review: Rhabdomyolysis -- an overview for clinicians. Crit Care. Apr 2005;9(2):158-69. [Medline].

  7. Brown CV, Rhee P, Chan L, et al. Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference?. J Trauma. Jun 2004;56(6):1191-6. [Medline].

  8. David WS. Myoglobinuria. Neurol Clin. Feb 2000;18(1):215-43. [Medline].

  9. Fujii K, Minami N, Hayashi Y, et al. Homozygous female Becker muscular dystrophy. Am J Med Genet A. May 2009;149A(5):1052-5. [Medline].

  10. Giannoglou GD, Chatzizisis YS, Misirli G. The syndrome of rhabdomyolysis: Pathophysiology and diagnosis. Eur J Intern Med. Mar 2007;18(2):90-100. [Medline].

  11. Kilfoyle D, Hutchinson D, Potter H, George P. Recurrent myoglobinuria due to carnitine palmitoyltransferase II deficiency: clinical, biochemical, and genetic features of adult-onset cases. N Z Med J. Feb 25 2005;118(1210):U1320. [Medline].

  12. Lin AC, Lin CM, Wang TL, Leu JG. Rhabdomyolysis in 119 students after repetitive exercise. Br J Sports Med. Jan 2005;39(1):e3. [Medline].

  13. Malinoski DJ, Slater MS, Mullins RJ. Crush injury and rhabdomyolysis. Crit Care Clin. Jan 2004;20(1):171-92. [Medline].

  14. Melli G, Chaudhry V, Cornblath DR. Rhabdomyolysis: an evaluation of 475 hospitalized patients. Medicine (Baltimore). Nov 2005;84(6):377-85. [Medline].

  15. Ocana J, Echarri R, Liano F. Rhabdomyolysis. Am J Kidney Dis. Jan 2006;47(1):A32, e1-2. [Medline].

  16. Sharp LS, Rozycki GS, Feliciano DV. Rhabdomyolysis and secondary renal failure in critically ill surgical patients. Am J Surg. Dec 2004;188(6):801-6. [Medline].

Further Reading

Keywords

rhabdomyolysis, acute renal failure, ARF, hyperkalemia, hypocalcemia, myoglobinuria, tubular obstruction, acute renal insufficiency, crush injury, muscle necrosis, viral myositis, connective tissue disease, hyperkalemia, hypocalcemia, multiorgan failure, potassium deficiency, sepsis, acute tumor lysis syndrome, autoimmune vesiculitis, dermatomyositis, ischemic pressure necrosis, external myolysis, gas gangrene, tetanus, Legionnaire disease, shigellosis, coxsackie viral infections, diabetic ketoacidosis, myxedema, nonketotic hyperosmolar comas, McArdle syndrome, muscular dystrophy, polymyositis, myophosphorylase, phosphofructokinase, phosphohexoisomerase deficiency, Reye syndrome

Contributor Information and Disclosures

Author

Prasad Devarajan, MD, Louise M Williams Endowed Chair in Pediatrics, Professor of Pediatrics and Developmental Biology, Director of Nephrology and Hypertension, Director of Clinical Nephrology Laboratories, Chief Executive Officer of Dialysis Unit, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine
Prasad Devarajan, MD is a member of the following medical societies: American Heart Association, American Society of Nephrology, American Society of Pediatric Nephrology, National Kidney Foundation, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Coauthor(s)

Watson C Arnold, MD, Director, Department of Pediatric Nephrology, Cook Children's Medical Center
Watson C Arnold, MD is a member of the following medical societies: American College of Medical Quality, American Federation for Medical Research, American Society for Nutritional Sciences, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, Sigma Xi, Southern Society for Pediatric Research, Texas Medical Association, and Texas Pediatric Society
Disclosure: Nothing to disclose.

Medical Editor

Laurence Finberg, MD, Clinical Professor, Department of Pediatrics, University of California at San Francisco and Stanford University
Laurence Finberg, MD is a member of the following medical societies: American Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Frederick J Kaskel, MD, PhD, Director of the Division and Training Program in Pediatric Nephrology, Vice Chair, Department of Pediatrics, Montefiore Medical Center and Albert Einstein School of Medicine
Frederick J Kaskel, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Pediatric Society, American Physiological Society, American Society of Nephrology, American Society of Pediatric Nephrology, American Society of Transplantation, Eastern Society for Pediatric Research, Federation of American Societies for Experimental Biology, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Renal Physicians Association, Sigma Xi, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Howard Trachtman, MD, Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine
Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD, The Isaac A Abt, MD, Professor of Kidney Diseases, Feinberg School of Medicine, Northwestern University; Division Head of Kidney Diseases, Children's Memorial Hospital, Chicago
Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology
Disclosure: Amgen Grant/research funds None; Altus Pharmaceuticals Grant/research funds None; Genzyme Grant/research funds None; Merck Grant/research funds None; NIH Grant/research funds None

 
 
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