A first in literature: anesthesia management in kidney transplant surgery of a patient with McArdle disease.

McArdle disease is an inherited myopathy that autosomal recessive inheritance and is also known as glycogen storage disease type 5. Myoglobinuria, increase in serum CK level and darkening of urine color secondary to myoglobinuria are typical. Patients may have symptoms associated with increased rhabdomyolysis secondary acute renal failure or hyperkalemia after long and strenuous exercise periods. Today, many studies in the literature have shown that transplantation is superior to dialysis in patients with end-stage renal disease. Our case is a 53-year-old male patient with the diagnosis of McArdle syndrome who was going to have a kidney transplant. The patient had essential hypertension and history of HBsAg+. Total intravenous anesthesia technique was chosen as the anesthesia technique because inhaled anesthetic agents may trigger malignant hyperthermia in the patient. We didn't experience any perioperative complications in our patient. In conclusion, renal transplantation performed with total intravenous in a McArdle syndrome patient may be a simple and effective technique.

Cilastatin Ameliorates Rhabdomyolysis-induced AKI in Mice.

BACKGROUND: Rhabdomyolysis, the destruction of skeletal muscle, is a significant cause of AKI and death in the context of natural disaster and armed conflict. Rhabdomyolysis may also initiate CKD. Development of specific pharmacologic therapy is desirable because supportive care is nearly impossible in austere environments. Myoglobin, the principal cause of rhabdomyolysis-related AKI, undergoes megalin-mediated endocytosis in proximal tubule cells, a process that specifically injures these cells. METHODS: To investigate whether megalin is protective in a mouse model of rhabdomyolysis-induced AKI, we used male C57BL/6 mice and mice (14-32 weeks old) with proximal tubule-specific deletion of megalin. We used a well-characterized rhabdomyolysis model, injection of 50% glycerol in normal saline preceded by water deprivation. RESULTS: Inducible proximal tubule-specific deletion of megalin was highly protective in this mouse model of rhabdomyolysis-induced AKI. The megalin knockout mice demonstrated preserved GFR, reduced proximal tubule injury (as indicated by kidney injury molecule-1), and reduced renal apoptosis 24 hours after injury. These effects were accompanied by increased urinary myoglobin clearance. Unlike littermate controls, the megalin-deficient mice also did not develop progressive GFR decline and persistent new proteinuria. Administration of the pharmacologic megalin inhibitor cilastatin to wild-type mice recapitulated the renoprotective effects of megalin deletion. This cilastatin-mediated renoprotective effect was dependent on megalin. Cilastatin administration caused selective proteinuria and inhibition of tubular myoglobin uptake similar to that caused by megalin deletion. CONCLUSIONS: We conclude that megalin plays a critical role in rhabdomyolysis-induced AKI, and megalin interference and inhibition ameliorate rhabdomyolysis-induced AKI. Further investigation of megalin inhibition may inform translational investigation of a novel potential therapy.

Discolored Urine in Horses and Foals.

This article describes the most common causes of urine discoloration. The review includes a description of the most common disorders causing hematuria, highlighting clinical presentation, treatments, and pathophysiology. Causes of hemoglobinuria and myoglobinuria together with their mechanisms of renal injury are also reviewed.

Pervitin Intoxication with Two-peak Massive Myoglobinemia, Acute Kidney Injury and Marked Procalcitonin Increase Not Associated with Sepsis.

Patients intoxicated with methamphetamine-like substances may present with myoglobinuria but rarely require admission. An 18-year-old female was admitted due to intoxication with pervitin, a methamphetamine derivative. She presented with an altered mental status, fever, and increased heart and respiratory rates. Biomarkers showed leukocytosis and markedly increased procalcitonin levels, suggestive of sepsis. However, blood cultures and infectious disease workup were unrevealing. Clinical course was heralded by rhabdomyolysis and myoglobinuria resulting in multi-organ failure including respiratory failure necessitating mechanical ventilation, hemodynamic compromise with need for inotropic support, and an acute renal failure requiring renal replacement therapy. Surprisingly, after a transient improvement, an unexpected second peak of myoglobin was observed on hospital day 5, controlled by intensifying the elimination methods, and administration of dantrolene. Acute kidney injury resolved by hospital day 15, and the patient could be discharged on day 22. While most patients with intoxications are discharged within 24 hours from emergency departments without being admitted, our case report highlights that the organ injury may evolve beyond the usual observation period, traditional renal-replacement therapies may not be sufficient to mitigate myoglobinemia with resulting acute kidney injury, and that procalcitonin may not be a reliable biomarker of infection in the setting of drug-induced rhabdomyolysis.

Use of dexamethasone in idiopathic, acute pediatric rhabdomyolysis.

Current rhabdomyolysis treatment guidelines vary based on the etiology and diagnosis, yet many cases evade conclusive diagnosis. In these cases, treatment options remain largely limited to fluids and supportive therapy. We present two cases of acute rhabdomyolysis diagnosed in the emergency department: a 5-year-old boy with sudden onset bilateral flank pain, and a 13-year-old boy with 2-3 days of worsening pectoral and shoulder pain. Each patient had a prior similar episode requiring hospitalization in the past. The 5-year-old had no inciting trauma or trigger, medication use, or illness. The 13-year-old previously had an upper respiratory infection during the week prior and had been strenuously exercising at the time of onset. Genetic testing results were unknown for both patients during their hospitalizations, and insurance and other barriers led to delay. Later results for the first patient revealed a heterozygous deletion in intron 19 on the LPIN1 gene interpreted as a variant of unknown significance. During their hospitalizations, both children were started on intravenous (i.v.) fluids, and creatine kinase (CK) initially trended downward, but then began to rise or plateau. After reviewing the cases, prior literature, and anecdotal evidence of benefit from corticosteroid therapy in rhabdomyolysis with our consultant metabolic physicians, dexamethasone was initiated. In both patients, dexamethasone use correlated with relief of patient symptoms, significantly decreased CK value, and our ability to discharge these patients home quickly. Our cases, discussion, and literature review all lead to the consideration of the use of dexamethasone in conjunction with standard therapy for acute rhabdomyolysis.

Acute recurrent rhabdomyolysis in a Chinese boy associated with a novel compound heterozygous LPIN1 variant: a case report.

BACKGROUND: LPIN1-related acute recurrent rhabdomyolysis (RM), first reported in 2008, is an autosomal recessive inherited metabolic disease. In recent years, LPIN1 gene variants have been identified as one of the main causes of severe RM in children in Western countries. The disease is extremely rare in China, and we report a case of acute recurrent RM caused by a novel compound heterozygous LPIN1 variant. CASE PRESENTATION: A 15-year-old Chinese boy presented with myalgia after strenuous exercise, accompanied by transient increases in serum creatine kinase and myoglobin and persistent hyperuricaemia and hyperbilirubinaemia. Genetic analysis using high-throughput genomic sequencing and Sanger sequencing revealed that there was a compound heterozygous variant in the LPIN1 gene of the proband: the paternal c.2047A > G(p.I683V) was an unreported missense variant, and the maternal c.2107_2108 insAGG(p.Q703delin sQE) was an unreported in-frame variant. CONCLUSIONS: In children with RM, LPIN1 variants should always be considered in the differential diagnosis. The clinical features of our case are atypical, which highlights the importance of an accurate diagnosis by genetic testing. If detected early, the condition may be controlled, and the prognosis may be improved.

Acute kidney injury in pediatric non-traumatic rhabdomyolysis.

BACKGROUND: Our study aimed to determine the prevalence of acute kidney injury (AKI) in pediatric non-traumatic rhabdomyolysis, and to identify factors associated with its development. METHODS: Clinical information and laboratory tests of children with rhabdomyolysis who were admitted between 2009 and 2018 were reviewed retrospectively. Rhabdomyolysis was defined by a peak serum creatine kinase (CK) level > 1000 IU/L within the first 72 h of admission. The primary outcome was the occurrence of AKI within the first 7 days of admission, which was determined by the KDIGO criteria. RESULTS: A total of 54 patients with a median age of 7.8 years old were included. Ten (18.5%) patients developed AKI. AKI was relatively rare in children with viral myositis (2.6%), whereas all patients with rhabdomyolysis related to seizure or irritability/dystonia developed AKI. Patients with AKI had higher white cell count (10.6 vs. 4.5 × 109/L) and lower serum bicarbonate (19.4 vs. 25.5 mmol/L) on admission, with higher peak serum CK (23,086.0 vs. 3959.5 IU/L). The AKI group was more likely to present with positive urine results (myoglobinuria, dipstick heme or protein ≥ 2+). Peak serum CK had a good discriminatory power for stage 2-3 AKI (AUC 0.930, p = 0.005), with an optimal cut-off of 15,000 IU/L identified from the ROC analysis. CONCLUSIONS: The overall prevalence of AKI in pediatric non-traumatic rhabdomyolysis was 18.5%. Positive urine tests (myoglobinuria, dipstick heme or protein ≥ 2+), high white cell count, lower serum bicarbonate on admission, and high peak serum CK were associated with development of AKI.

Exercise Induced Myoglobinuria is Determined by Haptoglobin Polymorphism.

BACKGROUND: In professional soccer players (n = 27), confounders of quantitative myoglobinuria following physical training were assessed in order to improve interpretation of post-exercise myoglobinuria. METHODS: Urine samples were collected in the morning before training sessions, 48 to 72 hours following a game. Urine myoglobin was assayed using immunoturbidimetry. Blood was drawn 48 hours following training session. Creatinine was assayed using a Jaffe method. Creatine kinase (CK) activity was assayed according to the IFCC reference method. Serum myoglobin was assayed using the same assay as the one used for urine. Hp polymorphism was assessed on hemoglobin supplemented serum. Serum Hp concentration was assayed nephelometrically. Training intensity was assessed using a wearable GPS tracking system. Physical load monitoring included the covered total distance, the distance at different speed zones, and the number of sprints/accelerations/decelerations/jumps. Multiple regression analysis was used to detect the determinants of post-exercise myoglobinuria. RESULTS: Myoglobinuria negatively correlated with serum haptoglobin (Hp) concentration. Athletes presented with Hp values, which were lower than the Hp phenotype reference ranges, which can be explained by depletion of circulating Hp stores. Myoglobinuria was most pronounced in players carrying a Hp 2-2 phenotype, which is associated with the lowest Hp reference range. Myoglobin clearance was inversely correlated with Hp 2-2 concentration. Correlation between myoglobinuria and biomarkers of muscle damage was weak. Neither age nor glomerular filtration rate were found to be confounders of myoglobinuria. When comparing myoglobinuria with training intensity, the number of sprints, average acceleration speed, and maximal speed were determining factors for predicting exercise-induced myoglobinuria. CONCLUSIONS: In athletes, plasma myoglobin binding capacity is depleted. Moderate myoglobinuria not only should be regarded as a muscle damage marker, but also should be interpreted as an indicator for Hp depletion. Apart from its significance as a biomarker for muscle damage and rhabdomyolysis, myoglobinuria in athletes should be a warning that the heme binding capacity of plasma Hp is depleted, indicating an exhausted defense against Fenton chemistry induced free radicals. Fenton chemistry is associated with free radical formation, which is to be avoided because of the causative relationship with inflammatory processes and tissue damage.

Malignant hyperthermia 2020: Guideline from the Association of Anaesthetists.

Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri-operative management of the patients.

Histopathological kidney changes and myoglobinuria in neotropical non-human primates attacked by dogs, Brazil.

BACKGROUND: Non-human primates (NHPs) are susceptible to dogs' attacks, events that may cause muscle damage along with stress, and could be in some extent compatible with capture myopathy, a syndrome that results in myoglobinuria and renal damage. METHODS: We aimed to evaluate by histopathology pre-existing lesions and subsequent sequelae related to dogs' attacks, acute tubular necrosis (ATN) and myoglobinuria, as well as the usefulness of Pearls Stain and IHC to diagnose it. Histopathology was performed in available organs, and sections of kidney submitted to Prussian blue stain and myoglobin immunohistochemistry. RESULTS: During January 2014-June 2016, 16/145 (11%) of NHPs received by Adolfo Lutz Institute, Brazil were reported as attacked by dogs. A high frequency of young and debilitated animals was found. Myoglobinuria was observed in more than half animals (9/16; 56.2%), from which (5/9; 55.5%) presented ATN. CONCLUSIONS: Kidney lesions are plausible findings in NHPs attacked by dogs.

Outcome of Benign Acute Childhood Myositis: The Experience of 2 Large Tertiary Care Pediatric Hospitals.

OBJECTIVE: The aims of the study were to determine the evolution of benign acute childhood myositis in children and to assess the relationship between creatine phosphokinase (CPK) values and myoglobinuria. STUDY DESIGN: A retrospective study of patients with benign acute childhood myositis seen in 2 tertiary care university-affiliated pediatric hospitals during overlapping 4-year periods. METHODS: Demographic data, historical details, clinical, and laboratory results were extracted from the charts of children younger than 16 years with a CPK greater than 3 times normal. Complications, treatments, and outcomes were recorded. RESULTS: Fifty-four children were included, 43 (80%) were male, and mean age was 7.3 years (median [range], 6 [3-16] years), none showed abnormal neurological findings, manifested hematuria, or developed renal failure. Mean CPK level at presentation was 1872 IU/L (range, 511-8086 IU/L). None developed renal failure, and there were no adverse outcomes on follow-up. CONCLUSIONS: Acute childhood myositis is a predominantly benign disease. Neurological examination is usually normal and rhabdomyolysis is rare. Although severe pathological comorbid conditions must be excluded, a complete history and examination, coupled with simple blood and urine tests, can help minimize unnecessary diagnostic investigations.

Severe myoglobinuric acute kidney injury in a kidney recipient: rapid recovery after hemodialysis with the super high-flux membrane Theralite®â€©.

Myoglobinuric acute kidney injury (AKI) is a severe condition requiring early therapeutic strategies. Early recognition and treatment are crucial to reduce morbidity and mortality rate. Here, we report a kidney recipient with severe rhabdomyolysis and AKI secondary to parvovirus B19 infection. Initiation of hemodialysis with the super high-flux filter Theralite® (Gambro, cut-off 45 kDa, 2.1 m2) resulted in the clearance of myoglobin from 61 to 71% after 3 hours. Elimination rates of IL-6 and ß2-microglobulin were ~ 30 - 64% and 55 - 71% after 3 hours, respectively. Renal graft function rapidly recovered. The place of this effective but expensive procedure still needs to be defined and validated in high-risk patients.
.

Young girl presenting with exercise-induced myoglobinuria.

INTRODUCTION: The sarcoglycanopathies are a heterogeneous group of autosomal recessive limb-girdle muscular dystrophies that cause varying degrees of progressive proximal muscle weakness. METHODS: We describe the case of a Caucasian girl who presented with exercise intolerance, myalgia, and dark urine. Onset of symptoms was at age 4, and she had myalgia with physical activity throughout childhood. Creatine kinase levels were as high as 18,000. RESULTS: Immunostaining of a muscle biopsy showed mildly diminished alpha sarcoglycan staining, and SGCA gene sequencing revealed n.C229T; p.Arg77Cys (R77C) and n.C850T; p.Arg284Cys (R284C), which is associated with alpha sarcoglycanopathy. CONCLUSIONS: This patient presented with exercise intolerance, myoglobinuria, and almost normal muscle strength into adolescence, which is uncommon in sarcoglycanopathies. This uncommon presentation should be kept in mind, so that early recognition and intervention may prevent future comorbidities and help preserve the quality of life. Muscle Nerve 54: 161-164, 2016.

Severe rhabdomyolysis secondary to adenovirus infection: case report and literature review.

A 38-year-old male presented with renal failure in the setting of a flu-like illness. Urinalysis showed myoglobinuria and granular casts. His serum creatine phosphokinase was markedly elevated. He was diagnosed with rhabdomyolysis and was volume resuscitated with normal saline and bicarbonate-containing fluid. Workup included a respiratory viral panel which was positive for adenovirus. Other causes such as trauma, seizure, and intoxicants were excluded. He developed progressive renal failure necessitating hemodialysis. After ~ 4 weeks he recovered renal function and dialysis was discontinued. Viral-induced myopathy should be suspected in patients who present with rhabdomyolysis.

The effect of hyperbaric oxygen therapy on rhabdomyolysis-induced myoglobinuric acute renal failure in rats.

Myoglobinuric acute renal failure (MARF) may develop after severe muscle injury. Heme oxygenase-1 (HO-1), a stress-response protein, has been implicated as a protective agent against MARF. We hypothesized that hyperbaric oxygen therapy (HBOT) may alleviate MARF by inducing renal HO-1 expression. Wistar-Albino rats were randomly assigned into three groups: Control (n = 4), MARF (n = 8), MARF + HBO (n = 8). MARF was induced by intramuscular glycerol (50%, 8 mL/kg) injection. Saline (8 mL/kg) was injected into the hind limb of the animals in the control group. Animals in the MARF + HBO group received two sessions of HBO therapy (90 min at 2.5 atm) 2 and 18 h after glycerol injection. Serum and tissue samples were taken at 24 h. Serum urea and creatinine levels increased in the MARF and MARF + HBO groups confirming the development of MARF. But, serum urea and creatinine levels were similar in MARF and MARF + HBO groups. Oxidative stress parameters were similar among all groups. Histological renal injury score was similar in MARF and MARF + HBO groups. HO-1 level, determined by immunohistochemistry, was significantly higher in MARF and MARF + HBO groups, compared to the control group. Although HO-1 level in MARF + HBO group was higher than MARF group, it was not statistically significant. We found that HBOT did not reduce renal injury in experimental MARF model. HBOT is used to reduce the muscle damage after crush injury, which may be accompanied by MARF. Therefore, more studies are needed to understand the effects of HBO treatment on renal functions after MARF.

[Brown urine : Myoglobin-induced renal failure after concomitant administration of simvastatin and amiodarone]. / Brauner Urin : Myoglobininduziertes Nierenversagen nach gleichzeitiger Gabe von Simvastatin und Amiodaron.

Rhabdomyolysis is a rare but well-known complication of statin therapy. The risk is considerably increased when concomitant drugs are administered that inhibit metabolism and breakdown via the cytochrome CYP3A4. We report a case of myoglobin-induced acute renal failure secondary to the concomitant use of simvastatin and amiodarone. The risk of rhabdomyolysis is mainly determined by the statin dose; in the case of the concomitant use of CYP3A4 inhibitors, a maximal daily dose of 20 mg is recommended to avoid harmful drug interactions.

Fatal rhabdomyolysis after torture by reverse hanging.

PURPOSE: Reverse hanging (also known as Palestinian hanging) is a form of positional torture where the victim is suspended for a prolonged period of time by the wrists, after the wrists are bound at the back. We report the first autopsy case of reverse hanging. We have discovered that fatal myoglobinuric renal failure due to rhabdomyolysis can be a complication of Palestinian hanging. METHOD: An adult detainee, who underwent interrogation by authorities, was admitted to hospital from a prison and died in hospital after a few days. Death was due to myoglobinuric renal failure. An autopsy was performed. RESULTS: At autopsy, the body showed anasarca due to renal failure. There were healing ligature marks on the wrist and forearm, but no blunt impact injury to the shoulders or arms. There was extensive necrosis of the pectoralis major, biceps, and deltoid muscles, organizing hemoarthrosis of the right glenohumeral joint and hemorrhage into the joint capsule of the both glenohumeral joints. The kidneys showed evidence of myoglobin deposition grossly. The overstretching of the major muscles of the shoulder, in response to the prolonged Palestinian hanging, gave rise to the muscle necrosis. CONCLUSION: This case underscores the importance of conducting autopsies on people who die in custody, particularly if detained at times of political instability when torture may be practiced by state actors and others. This case also reveals that fatal rhabdomyolysis can occur by positional torture in a stress position, despite the absence of direct trauma due to blunt impacts.

Metabolic Myoglobinuria.

One large group of hereditary myopathies characterized by recurrent myoglobinuria, almost invariably triggered by exercise, comprises metabolic disorders of two main fuels, glycogen and long-chain fatty acids, or mitochondrial diseases of the respiratory chain. Differential diagnosis is required to distinguish the three conditions, although all cause a crisis of muscle energy. Muscle biopsy may be useful when performed well after the episode of rhabdomyolysis. Molecular genetics is increasingly the diagnostic test of choice to discover the underlying genetic basis.

Changes in acute biochemical markers of inflammatory and structural stress in rugby union.

Rugby union is a sport governed by the impacts of high force and high frequency. Analysis of physiological markers following a game can provide an understanding of the physiological response of an individual and the time course changes in response to recovery. Urine and saliva were collected from 11 elite amateur rugby players 24 h before, immediately after, and at 17, 25, 38, 62 and 86 h post-game. Myoglobin, salivary immunoglobulin A and cortisol were analysed by ELISA, whereas neopterin and total neopterin were analysed by high-performance liquid chromatography. There was a significant post-game increase of all four markers. The increases were cortisol 4-fold, myoglobin 2.85-fold, neopterin 1.75-fold and total neopterin 2.3-fold when corrected with specific gravity. All significant changes occurred post-game only, with markers returning to and remaining at baseline within 17 h. The intensity of the game caused significant changes in key physiological markers of stress. They provide an understanding of the stress experienced during a single game of rugby and the time course changes associated with player recovery. Neopterin provides a new marker of detecting an acute inflammatory response in physical exercise, while specific gravity should be considered for urine volume correction post-exercise.