Higher Creatine Kinase Concentrations Research Articles

Carnitine palmitoyltransferase II deficiency and post-COVID vaccination rhabdomyolysis.

Carnitine palmitoyltransferase II (CPT II) deficiency is a disorder affecting fatty acid oxidation. The myopathic form of the condition is the most common among adults and manifests itself with a high serum creatine kinase (CK) concentration. Triggers of very high CK concentrations include periods of fasting, infection, exercise, stress, and exposure to extreme temperatures.A 27-year-old man known to have CPT II deficiency presented feeling generally unwell after his COVID-19 vaccine. His CK concentration of 105,000 U/L and deranged liver function tests (ALT 300 U/L and AST 1496 U/L) were in keeping with rhabdomyolysis. His biochemical parameters and myopathy resolved with continuous intravenous dextrose 10% and a high carbohydrate diet.Caution should be exercised when administering vaccinations (including the COVID-19 vaccination) to this population. Clinicians should be wary for signs and symptoms of CPT II deficiency exacerbations and be vigilant in monitoring serum CK.

Optimum polygenic profile to resist exertional rhabdomyolysis during a marathon.

PurposeExertional rhabdomyolysis can occur in individuals performing various types of exercise but it is unclear why some individuals develop this condition while others do not. Previous investigations have determined the role of several single nucleotide polymorphisms (SNPs) to explain inter-individual variability of serum creatine kinase (CK) concentrations after exertional muscle damage. However, there has been no research about the interrelationship among these SNPs. The purpose of this investigation was to analyze seven SNPs that are candidates for explaining individual variations of CK response after a marathon competition (ACE = 287bp Ins/Del, ACTN3 = p.R577X, CKMM = NcoI, IGF2 = C13790G, IL6 = 174G>C, MLCK = C37885A, TNFα = 308G>A).MethodsUsing Williams and Folland’s model, we determined the total genotype score from the accumulated combination of these seven SNPs for marathoners with a low CK response (n = 36; serum CK <400 U·L-1) vs. marathoners with a high CK response (n = 31; serum CK ≥400 U·L-1).ResultsAt the end of the race, low CK responders had lower serum CK (290±65 vs. 733±405 U·L-1; P<0.01) and myoglobin concentrations (443±328 vs. 1009±971 ng·mL-1, P<0.01) than high CK responders. Although the groups were similar in age, anthropometric characteristics, running experience and training habits, total genotype score was higher in low CK responders than in high CK responders (5.2±1.4 vs. 4.4±1.7 point, P = 0.02).ConclusionMarathoners with a lower CK response after the race had a more favorable polygenic profile than runners with high serum CK concentrations. This might suggest a significant role of genetic polymorphisms in the levels of exertional muscle damage and rhabdomyolysis. Yet other SNPs, in addition to exercise training, might also play a role in the values of CK after damaging exercise.

Compartment syndrome and rhabdomyolysis as a positioning complication following retrosigmoid craniotomy

The goal of surgical positioning is to provide optimal surgical access and visualization while maintaining the patient's safety, with the least physiological compromise. Here, we report a 30-year-old man with an unremarkable past medical history who developed superior vena cava syndrome after a 15-hour retrosigmoid craniotomy for removal of a right cerebellopontine (CP) angle tumor. Compartment syndrome from the head to neck and rhabdomyolysis were recognized, with extensive swelling of his head and neck, markedly swollen soft tissues and necrosis of multiple muscles revealed by computed tomography, and very high concentrations of creatine kinase (CK) and aspartate transaminase. Immediate intensive care and rehabilitation therapy were provided and aimed at maintaining adequate perfusion/oxygenation and decreasing tissue pressure. He was successfully weaned from ventilation on postoperative day (POD) 25, transferred to a general ward on POD 29, and discharged with mild muscular and neurological sequelae on POD 51. Careful adjustment of surgical positioning is crucial for patient safety, especially when positioned at an extreme position in association with prolonged surgery.

Urine dipstick analysis for identification of runners susceptible to acute kidney injury following an ultramarathon

This study examined whether urine dipstick testing might be useful to predict the development of acute kidney injury after an ultramarathon. Participants in the 2011 161-km Western States Endurance Run underwent post-race blood and urine dipstick analyses. Of the 310 race finishers, post-race urine dipstick testing was completed on 152 (49%) and post-race blood also was obtained from 150 of those runners. Based on “injury” and “risk” criteria for acute kidney injury of blood creatinine 2.0 and 1.5 times estimated baseline, respectively, 4% met the criteria for injury and an additional 29–30% met the criteria for risk of injury. Those meeting the injury criteria had higher creatine kinase concentrations (P < 0.001) than those not meeting the criteria. Urine dipstick tests that read positive for at least 1+ protein, 3+ blood, and specific gravity ≥ 1.025 predicted those meeting the injury criteria with sensitivity of 1.00 (95% confidence interval [CI] 0.54–1.00), specificity of 0.76 (95% CI 0.69–0.83), positive predictive value of 0.15 (95% CI 0.06–0.30), negative predictive value of 1.00 (95% CI 0.97–1.00), and likelihood ratio for a positive test of 4.2. We conclude that urine dipstick testing was successfully able to identify those individuals meeting injury criteria for acute kidney injury with excellent sensitivity and specificity.

Increasing Creatine Kinase Concentrations at the 161-km Western States Endurance Run

Very high blood creatine kinase (CK) concentrations have been observed among recent finishers of the 161-km Western States Endurance Run (WSER), and it has been suggested that there is a link between rhabdomyolysis and hyponatremia. Therefore, the purpose of this study was to compare CK concentrations of finishers in the 2010 WSER with past values, and to determine whether there was an association between blood CK and sodium concentrations. Consenting 2010 WSER finishers provided blood samples at the finish for determination of blood CK and sodium concentrations. Finish time, age, and gender were obtained from official race results, and running experience was determined from our database as number of prior 161-km ultramarathon finishes. From 216 (66%) of the 328 finishers, median and mean CK concentrations were found to be 20 850 IU/L and 32 956 IU/L, respectively (range 1500-264 300 IU/L), and 13 (6%) had values greater than 100 000 IU/L. These values were statistically higher (P < .0001) than those reported from the 1995 WSER. The CK concentration was not significantly associated with finish time, age, gender, or running experience. Blood sodium concentrations were obtained from a subgroup of 159 runners, and the relationship between blood CK and sodium concentrations did not reach statistical significance (P = .06, r = -0.12). Creatine kinase concentrations of 2010 WSER finishers are higher than values previously reported. More research should focus on explaining this observation and on whether there is a possible link between higher CK concentrations and hyponatremia.

Cardiac magnetic resonance imaging and management of dilated cardiomyopathy in a Duchenne muscular dystrophy manifesting carrier

JO N 3055 muscles. Most DMD boys initially present delayed motor milestones, elevated serum creatine kinase (CK), respiratory impairment and 25 % of those surviving the age of 15 present dilated cardiomyopathy and arrhythmias [3, 4, 8, 10]. Echocardiography describes left ventricular dysfunction, but cardiac magnetic resonance (CMR) can detect the earliest signs of cardiomyopathy: occult regional cardiac asynergy; tissue degeneration; fibrosis [1, 9, 12]. Standard therapy for heart failure is effective in DMD cardiomyopathy [7, 10]. Female carriers show a mosaic pattern of dystrophin-positive and dystrophin-negative muscular fibres. About 50 % of patients present skeletal muscular symptoms and 18 % present dilated cardiomyopathy, because of a “skewed Xinactivation”, with most cells having an active faulty X-chromosome [5, 6]. A 27-year old woman was referred to our hospital in 2005 because of fatigue, effort dyspnoea (NYHA class IIb), episodes of palpitations and near syncope. Two brothers with a typical history of DMD without heart involvement died in their teens due to respiratory failure. Her asymptomatic 6year old daughter had a mild increase of CK (640 U/L). DNA analysis revealed dystrophin gene deletion of exons 3–17. Electromyography showed small duration motor unit potentials and reduced amplitude interference pattern during voluntary contraction. In 2003, she had already been diagnosed with a dilated cardiomyopathy, with an echocardiographic ejection fraction (EF) of 40 %, treated discontinuously with carvedilol 6.25 mg b.i.d. She was a smoker (5 cigarettes/d) and showed only calf pseudohypertrophy. She had high plasmatic concentrations of CK (1745 U/L, n.v. 22– 269), normal levels of cardiac troA. Barison G. D. Aquaro C. Passino M. Falorni A. Balbarini M. Lombardi L. Pasquali M. Emdin G. Siciliano

Changes in Clinical Enzyme Activity and Bile Acid Levels in Psittacine Birds With Altered Liver Function and Disease

The diagnosis of hepatic disease in psittacine birds by using biochemical enzyme and bile acid levels is problematic. In this study, we looked at changes in clinical enzyme concentrations, bile acid levels, and plasma protein electrophoresis results to determine whether these analytes correlate with hepatic disease. A total of 442 samples representing 8 species of psittacine birds were analyzed for levels of bile acids, aspartate aminotransferase (AST), and creatine kinase (CK) and for changes in plasma protein concentrations determined by electrophoresis. Follow-up questionnaires were received from the submitting veterinarian detailing the diagnosis of the patient and whether liver disease had been confirmed by histologic examination. When the data were examined without regard to diagnosis, high clinical enzyme concentrations correlated poorly with high levels of bile acids. These results suggest that the often used corollary of high AST and normal CK concentrations as a sole screening test to evaluate hepatocellular injury is not valid. High bile acid levels had the highest association with confirmed hepatic disease, followed by high concentrations of alpha2-globulins, AST, lactate dehydrogenase (LDH), and alpha1-globulins.

Calcium Transients and the Effect of a Photolytically Released Calcium Chelator during Electrically Induced Contractions in Rabbit Rectococcygeus Smooth Muscle

Intracellular Ca 2+ was determined with the fura-2 technique during electrically induced contractions in the rabbit rectococcygeus smooth muscle at 22°C. The muscles were electrically activated to give short, reproducible contractions. Intracellular [Ca 2+] increased during activation; the increase in [Ca 2+] preceded force development by ∼2 s. After cessation of stimulation Ca 2+ fell, preceding the fall in force by ∼4 s. The fluorescence properties of fura-2 were determined with time-resolved spectroscopy using synchrotron light at the MAX-storage ring, Lund, Sweden. The fluorescence decay of free fura-2 was best described by two exponential decays (time constants ∼0.5 and 1.5 ns) at low Ca 2+ (pCa 9). At high Ca 2+ (pCa 4.5), fluorescence decay became slower and could be fitted by one exponential decay (1.9 ns). Time-resolved anisotropy of free fura-2 was characteristic of free rotational motion (correlation time 0.3 ns). Motion of fura-2 could be markedly inhibited by high concentrations of creatine kinase. Time-resolved spectroscopy measurements of muscle fibers loaded with fura-2 showed that the fluorescence lifetime of the probe was longer, suggesting an influence of the chemical environment. Anisotropy measurements revealed, however, that the probe was mobile in the cells. The Ca 2+-dependence of contraction and relaxation was studied using a photolabile calcium chelator, diazo-2, which could be loaded into the muscle cells in a similar manner as fura-2. Photolysis of diazo-2 leads to an increase in its Ca 2+-affinity and a fall in free Ca 2+. When muscles that had been loaded with diazo-2 were illuminated with UV light flashes during the rising phase of contraction, the rate of contraction became slower, suggesting a close relation between intracellular Ca 2+ and the cross-bridge interaction. In contrast, photolysis during relaxation did not influence the rate of force decay, suggesting that relaxation of these contractions is not determined by the rate of Ca 2+ removal or due to an increased Ca 2+ sensitivity, but instead is limited by other processes such as deactivation by dephosphorylation or detachment of tension-bearing cross-bridges, possibly regulated by thin filament systems.

Ectopic Production of Creatine Kinase MB: Updated Evaluation by Mass Assays

There have been several reports of apparently high concentrations of creatine kinase (CK)-MB in the sera of cancer patients (1)(2)(3)(4). In several of these cases, the high activity resulted from the presence of macro CK types 1 and 2 (5). False-positive results for CK-MB can occur if nonspecific assays such as immunoinhibition are used (6). These atypical isoenzymes are not inhibited by anti-CK-B antibodies, and high apparent CK-MB activities are produced. Macro CK type 1 (CK-BB bound to IgG) migrates between CK-MM and -MB, whereas type 2 (polymeric mitochondrial CK) migrates cathodic to CK-MM and can be readily differentiated from CK-MB by electrophoresis (7). However, macro CK-BB linked to IgA can comigrate with CK-MB, and false-positive detection of MB is possible even with electrophoresis (8). Annesley and McKenna (9) published the one clear case of ectopic CK-MB production by a tumor, by demonstrating high concentrations of CK-MB in homogenized tumor tissue and ruling out the presence of macro CK forms by heat stability tests. We describe a second case in which persistently high concentrations of CK-MB were detected in a patient with metastatic cancer. CK isoforms, myoglobin, lactate dehydrogenase isoenzymes, and cardiac troponins T and I were used to rule out the presence of acute myocardial injury. A 71-year-old white man with a past medical history of coronary artery disease, acute myocardial infarction (AMI), hypertension, congestive heart failure, cerebrovascular accident, carotid stenosis, and atrial fibrillation presented to the Hospital of St. Raphael with a 4-day history …

Impact of transfusion of mediastinal shed blood on serum levels of cardiac enzymes

Infusion of shed mediastinal blood using an autotransfusion system is a widely applied technique of blood conservation in cardiac surgery. Serial determinations of serum creatine kinase (CK), its MB isoenzyme (CK-MB), and lactate hydrogenase (LDH) levels have been used to monitor perioperative myocardial injury. We investigated the impact of postoperative autotransfused blood infusion on serum levels of these enzymes. We performed a retrospective analysis of postoperative serum CK, CK-MB, and LDH levels of 300 patients who had elective uncomplicated aortocoronary bypass grafting. Shed mediastinal blood samples from 26 patients were analyzed for CK, CK-MB (enzymatic activity and mass), and LDH levels before infusion. High postoperative serum levels of CK and LDH were observed after infusion of autotransfused blood. Shed mediastinal blood contained extremely high levels of these enzymes, particularly from patients who had internal mammary artery dissection. There was a strong correlation (r = 0.96) between measured CK-MB enzyme activities and those calculated from the CK-MB mass units. Infusion of autotransfused blood containing high concentrations of CK and LDH results in elevated serum levels of these enzymes. Hemolysis, frequently present in shed blood, does not interfere with the routine biochemical assays for CK and CK-MB enzyme activities. Caution should be taken when postoperative cardiac enzyme levels are used to determine myocardial injury after aortocoronary bypass grafting if autotransfusion is used as a method of blood conservation.

Dystrophinopathy in Isolated Female Patients with Muscular Dystrophy

Immunohistochemical examination of dystrophin is suggested as a useful method for diagnosing Duchenne carriers for genetic counseling, in the absence of an index case. This study included 17 females with an age range of 6 to 17 (mean 11.97 +/- 3.81) years and without a family history of Duchenne muscular dystrophy but with varying symptoms of muscle disease, high creatine kinase concentrations, myopathic muscle biopsies, and normal karyotype. Clinical severity was scored according to neurological findings. Muscle ultrasonography, cardiac evaluation, and pathologic examination were done. Dystrophinopathy was detected in six cases (35.3%). All of these cases included 8-33% partially dystrophin-deficient fibers and four of them also had 2-23% deficient fibers. Three cases revealed a mosaic pattern of dystrophin staining. Neither age nor clinical findings correlated with dystrophinopathy; creatine kinase concentrations correlated significantly, however.

Dystrophinopathy in Isolated Female Patients with Muscular Dystrophy

Immunohistochemical examination of dystrophin is suggested as a useful method for diagnosing Duchenne carriers for genetic counseling, in the absence of an index case. This study included 17 females with an age range of 6 to 17 (mean 11.97 +/- 3.81) years and without a family history of Duchenne muscular dystrophy but with varying symptoms of muscle disease, high creatine kinase concentrations, myopathic muscle biopsies, and normal karyotype. Clinical severity was scored according to neurological findings. Muscle ultrasonography, cardiac evaluation, and pathologic examination were done. Dystrophinopathy was detected in six cases (35.3%). All of these cases included 8-33% partially dystrophin-deficient fibers and four of them also had 2-23% deficient fibers. Three cases revealed a mosaic pattern of dystrophin staining. Neither age nor clinical findings correlated with dystrophinopathy; creatine kinase concentrations correlated significantly, however.

Mitochondrial inclusions, similar to those found in mitochondrial myopathies, contain in cultured cardiomyocytes high concentrations of creatine kinase: M. Eppenberger-Eberhardt, I. Riesinger, Th. Wallimann, Institute for Cell Biology, ETH, Zürich, Switzerland

Mitochondrial inclusions, similar to those found in mitochondrial myopathies, contain in cultured cardiomyocytes high concentrations of creatine kinase: M. Eppenberger-Eberhardt, I. Riesinger, Th. Wallimann, Institute for Cell Biology, ETH, Zürich, Switzerland