-
Journal of the American Society of... Oct 2021Rhabdomyolysis, the destruction of skeletal muscle, is a significant cause of AKI and death in the context of natural disaster and armed conflict. Rhabdomyolysis may...
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.
Topics: Acute Kidney Injury; Animals; Apoptosis; Blood Urea Nitrogen; Cilastatin; Disease Models, Animal; Endocytosis; Glomerular Filtration Rate; Kidney Tubules, Proximal; Low Density Lipoprotein Receptor-Related Protein-2; Male; Mice; Mice, Knockout; Myoglobin; Myoglobinuria; Protease Inhibitors; Rhabdomyolysis
PubMed: 34341182
DOI: 10.1681/ASN.2020030263 -
Rhode Island Medical Journal (2013) Nov 2014Exercise-induced rhabdomyolysis, or exertional rhabdomyolysis (ER), is a clinical entity typically considered when someone presents with muscle stiffness, swelling, and... (Review)
Review
Exercise-induced rhabdomyolysis, or exertional rhabdomyolysis (ER), is a clinical entity typically considered when someone presents with muscle stiffness, swelling, and pain out of proportion to the expected fatigue post exercise. The diagnosis is confirmed by myoglobinuria, and an elevated serum Creatinine Phosphokinase (CPK) level, usually 10 times the normal range. However, an elevation in CPK is seen in most forms of strenuous exercise, up to 20 times the upper normal range. Therefore, there is no definitive pathologic CPK cut-off. Fortunately the dreaded complication of acute renal failure is rare compared to other forms rhabdomyolysis. We review the risks, diagnosis, clinical course and treatment for exercise- induced rhabdomyolysis.
Topics: Acute Kidney Injury; Creatine Kinase; Exercise; Humans; Myoglobinuria; Rhabdomyolysis; Risk Factors
PubMed: 25365815
DOI: No ID Found -
BMJ Case Reports Dec 2023Cefiderocol is a novel siderophore cephalosporin antibiotic. In the present case report, a woman in her 70s presented with a 1-week history of altered mental status and...
Cefiderocol is a novel siderophore cephalosporin antibiotic. In the present case report, a woman in her 70s presented with a 1-week history of altered mental status and progressive purulent discharge from a non-healing diabetic foot ulcer on her right heel. MRI of the right foot revealed chronic osteomyelitis of the calcaneum. Surgical debridement was performed, and the tissue cultures grew extensively drug resistant (XDR) , XDR and The patient received ampicillin-sulbactam and cefiderocol. The antibiotic treatment course was complicated by brown urine discolouration. Investigations were unrevealing for haemoglobinuria, myoglobinuria and bilirubinuria. A side effect from cefiderocol was suspected and subsequently discontinued. Her urine colour returned to its normal colour within 3 days of discontinuation of cefiderocol.
Topics: Female; Humans; Cefiderocol; Anti-Bacterial Agents; Cephalosporins; Pseudomonas Infections; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial
PubMed: 38103906
DOI: 10.1136/bcr-2023-258207 -
Tidsskrift For Den Norske Laegeforening... Jun 2019The soreness that commonly follows unaccustomed and strenuous exercise is unlikely to be due to inflammation of the muscles. However, the rarer and more serious... (Review)
Review
The soreness that commonly follows unaccustomed and strenuous exercise is unlikely to be due to inflammation of the muscles. However, the rarer and more serious exercise-induced rhabdomyolysis appears to have a different pathogenesis, with clinical signs including tissue inflammation and muscle cell death, as well as elevated creatine kinase and myoglobinuria. Soreness and rhabdomyolysis can both be caused by the same type of muscular activity.
Topics: Exercise; Humans; Inflammation; Muscle, Skeletal; Myalgia; Rhabdomyolysis
PubMed: 31238673
DOI: 10.4045/tidsskr.18.0727 -
Pediatric Emergency Care Dec 2021Repeated presentations of a rare symptom in a patient should make a physician stop and evaluate for rare conditions. This is a report of a teenager with multiple...
Repeated presentations of a rare symptom in a patient should make a physician stop and evaluate for rare conditions. This is a report of a teenager with multiple episodes of rhabdomyolysis and weakness. He was eventually diagnosed as having McArdle muscular dystrophy, or glycogen storage disease type V. His rhabdomyolysis has been severe, with a creatinine kinase level of >320,000 U/L, myoglobinuria, transaminitis, and elevated bilirubin. He has a low threshold for triggering rhabdomyolysis, such as doing an hour of aerobic exercise 2 days in a row. McArdle disease is a glycogen storage disorder in which the skeletal muscle cannot convert glycogen to glucose. Unlike other glycogen storage disorders, McArdle muscular dystrophy only affects the skeletal muscle, sparing the brain and visceral organs, leading to a vague phenotype. These patients have exercise intolerance, muscle cramps, and rhabdomyolysis. Many patients report loading with simple carbohydrates before exercise, as they have learned that this can increase their stamina. The vague symptoms can lead to decades of delay in diagnosis and significant mismanagement. Rhabdomyolysis is the most dangerous sign of McArdle disease, and it can lead to acute kidney injury, resulting in renal failure requiring dialysis in the severest cases.Rhabdomyolysis has numerous causes, but when it is recurrent, especially with seemingly insignificant triggers, one needs to develop a broader differential and pursue advanced testing. This testing can include specific exercise tests, genetic sequencing, and muscle biopsy. This case report will guide the clinician through the process of evaluating recurrent rhabdomyolysis, working through the differential diagnosis and testing options.1.
Topics: Acute Kidney Injury; Adolescent; Exercise; Glycogen Storage Disease Type V; Humans; Male; Muscle, Skeletal; Rhabdomyolysis
PubMed: 32205805
DOI: 10.1097/PEC.0000000000002079 -
Expert Review of Neurotherapeutics Dec 2020Metabolic myopathies comprise a clinically etiological diverse group of disorders caused by defects in cellular energy metabolism including the breakdown of... (Review)
Review
INTRODUCTION
Metabolic myopathies comprise a clinically etiological diverse group of disorders caused by defects in cellular energy metabolism including the breakdown of carbohydrates and fatty acids, which include glycogen storage diseases and fatty acid oxidation disorders. Their wide clinical spectrum ranges from infantile severe multisystemic disorders to adult-onset myopathies. To suspect in adults these disorders, clinical features such as exercise intolerance and recurrent myoglobinuria need investigation while another group presents fixed weakness and cardiomyopathy as a clinical pattern.
AREAS COVERED
In metabolic myopathies, clinical manifestations are important to guide diagnostic tests used in order to lead to the correct diagnosis. The authors searched in literature the most recent techniques developed. The authors present an overview of the most common phenotypes of Pompe disease and what is currently known about the mechanism of ERT treatment. The most common disorders of lipid metabolism are overviewed, with their possible dietary or supplementary treatments.
EXPERT COMMENTARY
The clinical suspicion is the clue to conduct in-depth investigations in suspected cases of metabolic myopathies that lead to the final diagnosis with biochemical molecular studies and often nowadays by the use of Next Generation Sequencing (NGS) to determine gene mutations.
Topics: Humans; Metabolism, Inborn Errors; Muscular Diseases
PubMed: 32941087
DOI: 10.1080/14737175.2020.1825943 -
Orphanet Journal of Rare Diseases May 2015Rhabdomyolysis (RM) is a clinical emergency characterized by fulminant skeletal muscle damage and release of intracellular muscle components into the blood stream... (Review)
Review
Rhabdomyolysis (RM) is a clinical emergency characterized by fulminant skeletal muscle damage and release of intracellular muscle components into the blood stream leading to myoglobinuria and, in severe cases, acute renal failure. Apart from trauma, a wide range of causes have been reported including drug abuse and infections. Underlying genetic disorders are also a cause of RM and can often pose a diagnostic challenge, considering their marked heterogeneity and comparative rarity.In this paper we review the range of rare genetic defects known to be associated with RM. Each gene has been reviewed for the following: clinical phenotype, typical triggers for RM and recommended diagnostic approach. The purpose of this review is to highlight the most important features associated with specific genetic defects in order to aid the diagnosis of patients presenting with hereditary causes of recurrent RM.
Topics: Genetic Predisposition to Disease; Humans; Phenotype; Rhabdomyolysis
PubMed: 25929793
DOI: 10.1186/s13023-015-0264-3 -
The Veterinary Clinics of North... Apr 2022This article describes the most common causes of urine discoloration. The review includes a description of the most common disorders causing hematuria, highlighting... (Review)
Review
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.
Topics: Animals; Hematuria; Hemoglobinuria; Horse Diseases; Horses; Myoglobinuria
PubMed: 35282957
DOI: 10.1016/j.cveq.2021.11.005