Hemoglobinuria

Q We would like to discontinue offering the lab test for myoglobinuria. Has this test been replaced by other tests such as serum creatine kinase (CK) and haptoglobin, or is it still necessary?

A Generally, the first step in the work-up of red or brown urine is urine centrifugation. If the red color is present only in the urine sediment and if the supernatant is clear, then the patient most likely has hematuria. If the supernatant is red, then a urine dipstick should be used to test for blood. If the supernatant is positive for blood, either myoglobin or hemoglobin is present.

Hemoglobin is relatively poorly filtered by the kidneys due both to its high molecular weight and to protein binding to haptoglobin. The kidneys filter only the unbound dimer, and hemoglobinuria will not occur until the filtered load exceeds proximal reabsorptive capacity. Although this does not require a high plasma concentration of the free dimer, the total hemoglobin concentration generally exceeds 100 mg/dL to 150 mg/dL, resulting in a red to brown color of the plasma. Myoglobin, in comparison, is a monomer, has a lower molecular weight, and is not protein bound. Thus, it is rapidly filtered and excreted, which allows the plasma to retain its normal color unless renal failure limits myoglobin excretion. In rhabdomyolysis, excess myoglobin is produced secondary to excess skeletal muscle breakdown. (1)

Typically, the triad of pigmented granular casts in the urine, a red to brown color of the urine supernatant, and a marked elevation in the plasma level of CK suggests the diagnosis of rhabdomyolysis. (2) In clinically asymptomatic rhabdomyolysis, however, diagnosis may be made on the basis of elevated serum CK, which is considered the most sensitive test for confirming the presence of muscle breakdown and injury. (1,2) Furthermore, early detection may be helpful in the prevention of acute tubular injury due to direct myoglobin-induced renal tubular toxicity. (1,3) Markedly elevated serum CK has been well correlated with the development of acute renal failure. (2)

For diagnosis of skeletal muscular injury, testing for serum and urine myoglobin is thought to be more specific but less sensitive than is testing for serum CK. A recent study found a poor correlation between urine myoglobin and the presence of significantly elevated serum myoglobin. Thus, myoglobin levels in neither serum nor urine provide the sensitivity necessary for the prompt institution of therapy for rhabdomyolysis; serum CK levels and correlation with the proper clinical setting remain the standard of care. (3)

--Frank Cruz III, MD

Department of Pathology

Oregon Health and Science University

Portland, OR

References

1. Grover DS, Atta MG, Eustace JA, Kickler TS, Fine DM. Lack of clinical utility of urine myoglobin detection by microconcentrator ultrafiltration in the diagnosis of rhabdomyolysis. Nephrol Dial Transplant. 2004;19:2634-2638.

2. Warren JD, Blumbergs PC, Thompson PD. Rhabdomyolysis: a review. Muscle Nerve. 2002;25:332-347.

3. Koppel C. Clinical features, pathogenesis and management of drug-induced rhabdomyolysis. Med Toxicol Adverse Drug Exp. 1989;4:108-126.

Daniel M. Baer, MD, is professor emeritus of laboratory medicine at Oregon Health and Science University in Portland, OR, and a member of MLO's editorial advisory board.

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