Urine Myoglobin Research Articles

Myoglobin in Urine

Myoglobin in Urine

Post-mortem urinary myoglobin levels with reference to the causes of death

To evaluate pathophysiological significance of post-mortem urinary myoglobin levels in determining the cause of death, we investigated 210 forensic autopsy cases, partially in comparison with serum levels. Post-mortem serum myoglobin levels were extraordinary high in most cases possibly due to post-mortem change. Urinary myoglobin levels did not correlate with the serum levels, showing possible post-mortem elevation in cases of a prolonged post-mortem period over 48 h. A high (>1000 ng/ml), moderate (100–1000 ng/ml), slight (50–100 ng/ml) and not significant (<50 ng/ml) elevation of urinary myoglobin were observed in 26, 43, 31 and 110 cases, respectively. Half the highly elevated cases were those with a survival time over 24 h. In cases of minor muscle injury such as head trauma, elevation of urinary myoglobin level was closely related to longer survival. In acute/subacute deaths with a post-mortem interval within 48 h, a significant difference was observed in relation to the blood carboxyhemoglobin (COHb) levels of fire victims: myoglobinuria over 100 ng/ml was more frequently and markedly observed in cases with COHb below 60% than over 60%, suggesting muscle damage in fatal burns. Similar elevation was observed in heat stroke victims, and also in some cases of acute and subacute death from polytrauma, asphyxiation, drowning, electricity and spontaneous cerebral bleeding, but not in myocardial infarction. Thus, it was suggested that high post-mortem urinary myoglobin levels in acute and subacute death cases may be a possible indicator of antemortem massive skeletal muscle damage as well as exertional muscle hyperactivity or convulsive disorders associated with hypoxia.

Biochemical investigation of suspected rhabdomyolysis

Rhabdomyolysis is a common condition in which injury to skeletal muscle results in leakage of the contents of myocytes into extravascular uid and, if severe enough, passage of suf®cient myoglobin into urine to colour it brown. There can be a concomitant sequestration of a large volume of extracellular uid within muscle tissue. It has been suggested that the ®rst reference to this condition occurs in the Book of Numbers but the earliest modern reports in man appear in the late 19th and early 20th centuries. Bywaters and Beall, after meticulous observations on four patients extricated from bomb-damaged buildings, ®rst described rhabdomyolysis leading to acute renal failure (ARF) as part of the crush syndrome. In these patients crushed limbs became swollen after extrication. There was marked vasoconstriction and hypotension followed by ARF, with urine containing many dark brown or black granular casts. Subsequent study of experimental muscle injury indicated that myoglobin contributes to ARF only in the presence of volume depletion and aciduria. Since then, rhabdomyolysis has been described in association with a host of traumatic injuries and non-traumatic conditions; it now seems as though almost every serious medical disorder may at times be associated with a degree of rhabdomyolysis, which is often not initially suspected. The occurrence of ARF following rhabdomyolysis has been put at between 17% and 33% of cases and accounts for between 3% and 15% of all cases of ARF. Against this background of serious complications of rhabdomyolysis, the clinical laboratory may be asked to make various measurements, including serum creatine kinase (CK), serum myoglobin and urine myoglobin, to answer three related questions: 1. Has this patient a signi®cant degree of rhabdomyolysis? 2. In a patient presenting with a dark urine, is the pigment myoglobin? 3. In a patient with rhabdomyolysis, can any measurements predict the development of ARF so that appropriate prophylactic measures can be instituted?

Rhabdomyolysis.

Rhabdomyolysis.

Malignant hyperthermia: advances in clinical management and diagnosis

Malignant hyperthermia: advances in clinical management and diagnosis

Monitoring myoglobin by capillary zone electrophoresis with end-column amperometric detection.

Capillary zone electrophoresis was employed for the determination of myoglobin in human urine using end-column amperometric detection with a carbon fiber microelectrode at a constant potential of 1.80 V vs. saturated calomel electrode (SCF). The optimum conditions of separation and detection are: 3.73 x 10-4 mol/L sodium diethyl malonyl urea (barbitone sodium), 1.34 x 10-4 mol/L HCl for the buffer solution, 20 kV for separation voltage, 5 kV and 5 s for injection voltage and injection time, respectively. The limit of detection is 4.4 x 10-8 mol/L or 84 amole signal to noise (S/N = 2). The relative standard deviation is 2.9% for the migration time and 2.5% for the electrophoretic peak current. The method can be used for the determination of myoglobin in human urine. The samples can be directly injected and need no pretreatment. The method is also rapid, less than 2 min, and has a recovery rate of 94-106%.

Early predictors of myoglobinuria and acute renal failure following electrical injury

Myoglobinuria-induced acute renal failure (ARF) is a potentially lethal consequence of electrical injury. We describe clinical variables that can predict the risk of myoglobinuria and ARF following electrical injury. This was a retrospective multivariate analysis of risk factors among electrically injured patients over a 26-year period. Urine myoglobin status was documented in 162 patients; 14% had myoglobinuria. No patient developed ARF. Multivariate modeling revealed that high-voltage exposure, prehospital cardiac arrest, full-thickness burns, and compartment syndrome were associated with myoglobinuria. Using a prediction rule defined as positive when a patient had ≥ 2 risk factors yielded a sensitivity of 96% and negative predictive value of 99%. Electrical injury patients with myoglobinuria have little risk of developing ARF. A prediction rule can be used to screen out patients at low risk for myoglobinuria and identify high-risk patients who warrant early aggressive treatment and a more definitive myoglobin test.

Effects of pH and urea on the determination of urinary myoglobin concentration by an enzyme immunoassay

Effects of pH and urea on the determination of urinary myoglobin concentration by an enzyme immunoassay

Biochemical, hematologic, and immunologic alterations following hepatic cryotherapy.

Hepatic cryosurgery causes hepatocellular damage primarily by inducing the formation of ice crystals. Cell necrosis is enhanced using two or more freeze-thaw cycles. The resultant damage to hepatocytes induces alterations in a number of biochemical and hematologic parameters, including hepatic function tests, serum bilirubin, serum and urine myoglobin, platelet count, and coagulation measures. Further, in experimental models, cryogenic surgery appears to stimulate the immune system of the host leading to an anti-tumor immune response. These perturbations in biochemical and hematologic parameters are usually transient, and long-term adverse sequelae are uncommon and preventable.

Stability of a Control Material Suitable for Quantitative Measurement of Urine Myoglobin

Myoglobin is a 17-kDa single-chain hemoprotein found in skeletal and cardiac muscle. This heme protein facilitates the movement of oxygen into cells and provides for local storage of oxygen. Myoglobin is found in the circulation as a result of muscle damage. Several conditions are associated with the release of myoglobin into the circulation, including myocardial infarction, trauma, ischemia, surgery, exercise, rhabdomyolysis, and other myopathy-associated disease states [1–3] . The quantitative measurement of myoglobin in urine is clinically important in diagnosing myoglobinuria, which can subsequently induce acute renal failure, particularly in posttrauma, surgery, and rhabdomyolysis patients. Recent studies have suggested that patients with a urine myoglobin concentration >20 000 μg/L, particularly with a decreased myoglobin clearance rate (<4 mL/min), are at increased risk for decreased renal function (4)(5). Although the mechanism for myoglobin-induced acute renal failure has not yet been elucidated, large amounts of myoglobin present in the tubules may precipitate, particularly under acidic conditions, resulting in increased intratubular pressure and, subsequently, the decreased glomerular filtration rate (6) and (or) free-radical generation from inorganic iron may cause renal damage (7). The identification of the early clinical sequelae of myoglobinuria is important for enabling administration of prophylactic treatment for acute renal failure (8). Quantitative methodologies, including automated immunoassays, …

SCHOOL-BASED CORPORAL PUNISHMENT PRESENTING AS EXERCISE INDUCED RHABDOMYOLYSIS 1782

As of 1994, corporal punishment in schools is prohibited in 27 American states including New York State. Two boys, aged 11and 12 years, developed rhabdomyolysis from excessive exercise used as corporal punishment they received in a New York City public school. Both boys were ordered to perform 150 push-ups by their gymnastics teacher as a punishment for running around the gymnasium. Both developed tender and swollen deltoid and pectoralis major muscles and both required hospitalization for five days for parenteral hydration and urinary alkalinization to prevent acute renal failure. Serum levels of creatine kinase (CK), aminotransferases (AST, ALT), lactate dehydrogenase (LDH), and urine myoglobin (Ur Myoglobin) are shown below:Table After educational intervention, school officials responded with a new policy that no student perform more than six push-ups at any one time. As demonstrated here, corporal punishment in schools still endangers the health of children even in those states where it is illegal. Pediatricians can contribute to the abolishment of corporal punishment by: (1) educating him/herself that it is still legal in many American states, (2) promoting public awareness, (3) educating school officials and parents regarding alternatives, such as positive reinforcement for good behavior, (4) detecting and reporting cases of such punishment in schools and encouraging parents to utilize their rights to request that their children not be punished, and (5) educating school personnel and parents about the potential adverse effects of excessive exercise.

Diclofenac-Induced Rhabdomyolysis

A case is described in which, after administration of diclofenac for 13 days for arthritis attributed to gout, the patient experienced erythema multiforme followed by muscle weakness, elevation of serum creatine phosphokinase (CPK) level from 101 to 83,770 U/L, 100% muscle isoenzyme, blood urea nitrogen (BUN) level from 15 to 87 mg/dL, creatinine level from 1.0 to 2.1 mg/dL and urine myoglobin level to 1,190 micrograms/dL (N < 1.2). The diagnosis was rhabdomyolysis due to diclofenac, with myoglobinuria resulting in mild renal failure. Treatment consisted of discontinuing diclofenac and administering sufficient fluids to prevent progression of myoglobinuric renal failure. Serum CPK level gradually returned to normal by day 50, BUN and creatinine levels by day 28, and muscle strength between day 90 and 180. Rhabdomyolysis due to diclofenac or to other nonsteroidal antiinflammatory drugs has not been reported.

Ultrafiltration discrepancies in recovery of myoglobin from urine

We investigated the efficiency, accuracy, and reliability of the ultrafiltration/dipstick methodology commonly used to diagnose myoglobinuria. Twenty-five myoglobin-containing urine specimens were filtered by centrifugation for 15 min at 1500g through a Centricon-30 membrane filter. Both the original specimen and filtrate were assayed for myoglobin. The amount of myoglobin recovered subsequent to filtration varied from <1-38%. This poor and variable recovery was independent of sample matrix or precentrifugation of the specimens. This was most critical for urine specimens with myoglobin concentrations <60 000 microg/L. Fourteen of 18 such filtrates had concentrations <350 microg/L, a concentration below which a negative result would be obtained by using conventional dipstick methods. Thus, the use of this procedure has the potential to misdiagnose patients with myoglobin concentrations associated with increased risk of subsequent renal dysfunction, in particular when urine myoglobin concentrations are <60 000 microg/L.

Adaptation of a Quantitative Immunoassay for Urine Myoglobin:Predictor in Detecting Renal Dysfunction

Myoglobinuria, subsequent to rhabdomyolysis, may cause acute renal failure. For this reason, many qualitative and quantitative tests have been developed for the detection of myoglobin in urine. The authors describe the adaptation and optimization of the Stratus II serum myoglobin immunoassay to quantify urine myoglobin. In addition, the assay was used to accurately determine urine myoglobin concentrations in subjects at potential risk for myoglobin-induced renal dysfunction and the results obtained compared to conventional qualitative methods for urine myoglobin. The assay demonstrated with-in run and between-run coefficient of variations (CVs) of 6.2% and 7.2%, respectively, was linear from 0-950 micrograms/L, demonstrated good recovery, and was free from interference by hemoglobin, creatinine, and urea. Specimens were diluted with 0.1 mol/L phosphate buffer, pH 9.0 containing 3% bovine serum albumin before analysis. Myoglobin was assayed on urine obtained from 30 patients suspected of having myoglobinuria. Fifteen of 17 patients with serum creatinine greater than 1.4 mg/dL had myoglobin concentrations greater than 20,000 micrograms/L, whereas the remaining 31 patients with normal serum creatinine had urine myoglobin concentrations of less than 18,000 micrograms/L. If serum creatinine is used as an indicator of renal function, it would appear that accurate measurement of urine myoglobin may facilitate identification of patients with increased susceptibility to myoglobin-induced acute renal failure.

Prone Position

Prone Position

Exogenous causes of myoglobinuria: review of 26 cases

In this article, I review various causes of exogenous myoglobinuria(MU) and its pathogenesis in 26 consecutive patients admitted to emergency room, Asan Medical Center and determine whether there is a relationship between concentration of urine myoglobin(Mb) and acute renal failure(ARF) as a complication of MU. Serum and urine Mb were measured by RIA using myoglobin kit(Daiichi, Inc., Tokyo, Japan). The most common disorder of MU was septic shock with hypotension, followed by crush syndrome, major arterial occlusion by thormbosis, alcohol intoxication with status epilepticus, intoxication of unidentified snake venom and drug ingestion. On the basis of this limited amount of data, there is a significant association between high concentration in urine Mb(> 300 ng/ml) and ARF(Fisher's exact test, p < 0.005). To minimize the chances of development of ARF, routine urine Mb levels should be checked on patients at risk, especially septic shock with hypotension.

Myoglobinuria detection by capillary electrophoresis.

Capillary electrophoresis was used in this study to separate urinary myoglobin from hemoglobin based on its electrophoretic mobility. Urine was applied directly without any treatment. The separation was accomplished in less than 7 min. Myoglobin extracted from human muscle tissues was separated, in a borate buffer 150 mM, pH 8.7 containing 0.5% polyethyleneglycol at 6 kV, into two peaks (MI and MII) which were also resolved far from hemoglobin. Upon standing at room temperature, MII converted into MI. Horse myoglobin eluted close to MI. The addition of polyethyleneglycol to the buffer enhanced the separation and increased the peak height of myoglobin. Optimum conditions for the separation are discussed. The method is suitable for routine clinical analysis because of its simplicity and speed.

The Risk of Rhabdomyolysis and Acute Renal Failure with the Patient in the Exaggerated Lithotomy Position

Rhabdomyolysis with subsequent renal failure has been well documented as a complication of major trauma. However, this complication from elective urological procedures is less well recognized. In 10 patients who underwent elective urethroplasty serum levels of creatine kinase and urinary myoglobin were examined preoperatively and postoperatively. These patients were placed in the lithotomy position for several hours and had minimal muscle dissection. Serum creatine kinase was noted to increase significantly postoperatively to greater than 1,000 units and in 1 patient myoglobin was detected in the urine. This finding indicates that there is, indeed, a risk of muscle injury and potential rhabdomyolysis in these patients from the use of the exaggerated lithotomy position.

Immunoassays for serum and urine myoglobin: myoglobin clearance assessed as a risk factor for acute renal failure

We compared four immunoassays for serum and urine myoglobin. Within-run CVs were 5-13%, with biases seen between assays. Myoglobin was stable for 1 month in serum and 12 days in urine when the pH was adjusted to between 8.0 and 9.5. Hemoglobin caused no interference. We assayed 91 pairs of serum and timed urine specimens from 41 patients admitted for acute trauma or rhabdomyolysis. Most were treated with mannitol and alkalinization. Upon initial presentations, 21 patients with either low serum myoglobin concentrations (< 400 micrograms/L) or high myoglobin clearances (> or = 4 mL/min) had normal creatinine clearances and no clinical evidence of renal disease. The remaining 20 had low myoglobin clearances. Seven were in rhabdomyolysis-induced acute renal failure, or subsequently developed this complication. We suggest that low myoglobin clearance may indicate a high risk for developing renal failure or may be an early marker for kidney dysfunction. Low myoglobin clearance may prove useful in indicating failure of prophylactic treatment to clear myoglobin.

COMPRESSED AIR INJURY OF THE COLON COMPLICATED BY RHABDOMYOLYSIS

We present a case of traumatic injury of the colon by compressed air. Elevated levels of urinary myoglobin, creatinine phosphokinase, lactate dehydrogenase, and glutamic oxaloacetic transaminase indicating rhabdomyolysis were noted. In this type of injury, rhabdomyolysis related to acute peripheral circulatory failure may occur because of obstruction of venous return to the heart following a great increase in intraperitoneal pressure.