Rhabdomyolysis and myoglobinuria following single induction dose of propofol in a dog.

OBJECTIVE: To report a case of rhabdomyolysis and myoglobinuria following single induction dose of propofol in a dog. CASE SUMMARY: A 5-year-old intact male Shih-Tzu dog was presented for pigmenturia occurring a few hours following anesthesia for comprehensive oral health assessment and treatment. After premedication with IV diazepam (0.5 mg/kg), anesthesia was induced with IV propofol (4 mg/kg) and maintained with isoflurane vaporized in oxygen. A few hours following recovery from anesthesia, the dog developed rhabdomyolysis and myoglobinuria associated with increased serum alanine aminotransferase and C-reactive protein concentrations, as well as mild hypokalemia and euglycemic glycosuria. Approximately 48 hours after IV fluid therapy, the dog was clinically normal, and myoglobinuria progressively resolved. NEW OR UNIQUE INFORMATION PROVIDED: This is the first case description of rhabdomyolysis and myoglobinuria following a single dose of injectable propofol.

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.

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.

Acute kidney injury associated with rhabdomyolysis in a patient with COVID-19.

Rhabdomyolysis is defined as the breakdown of skeletal muscle leading to the release of muscle contents into the extracellular fluid. Patients with rhabdomyolysis can be asymptomatic or have myalgia symptoms, weakness, myoglobinuria with dark urine, significant electrolyte imbalance, and acute kidney injury. Here we describe a case on acute kidney injury associated to rhabdomyolysis in a patient with COVID-19.

[Carnitin-Palmitoyl Transferase type 2 deficiency: a rare cause of acute renal failure due to rhabdomyolysis].

Fatty acid oxidation disorders are inborn errors of metabolism. One of the possible alterations involves the failure of the carnitin-based transport of long-chain fatty acids into the mitochondria, necessary for muscle metabolism in case of prolonged physical exertion. Three kinds of Carnitin-Palmitoyl Transferase type 2 (CPT2) deficiency have been described: a myopathic form, a severe infantile form and a neonatal form. The clinical picture is characterized by recurrent attacks of rhabdomyolysis, muscular pains and fatigue, secondary to a prolonged physical exercise and sometimes aggravated by intercurrent events. Rhabdomyolysis episodes are associated with a significant increase in creatine phosphokinase and myoglobinuria and may result in acute renal failure. Patients are usually asymptomatic during intercurrent periods. When acute renal failure from rhabdomyolysis arises after intense physical activity, it is therefore necessary to also investigate the presence of metabolic myopathies due to enzymatic deficiency.

An unusual case of gross myoglobinuria in a child following Russell's viper (Daboia russelii) envenomation.

Overt myoglobinuria associated with myotoxicity is a classic feature of sea snake envenomation. Russell's viper bites usually result in coagulopathy, neurotoxicity and nephrotoxicity but rarely myotoxicity has been reported, especially in the Sri Lankan variety (Daboia russelii). All those studies have demonstrated mild degree myotoxicity with microscopic level myoglobinuria. We report what is probably the first case of gross myoglobinuria in a child following a Russell's viper bite with biochemical evidence of significant myotoxicity well beyond the levels that have been previously reported.

Hemoglobinuria paroxística nocturna / Paroxysmal nocturnal hemoglobinuria

ResumenLa hemoglobinuria paroxística nocturna es una anemia hemolítica crónica, adquirida, poco común, que afecta con igual frecuencia ambos sexos. Se manifiesta a cualquier edad y con mayor incidencia en países del sudeste asiático. Es el resultado de la expansión clonal no maligna de células progenitoras hematopoyéticas. Se caracteriza por anemia hemolítica intravascular, tendencia a la trombosis y un componente variable de insuficiencia medular.Se asocia a otras patologías hematológicas como anemia aplásica y síndrome mielodisplásico. La citometría de flujo es el método de elección para diagnóstico. El eculizumab y el trasplante de médula ósea alogénico son las únicas terapias efectivas.

Abstract:Paroxysmal nocturnal hemoglobinuria is a rare acquired chronic hemolytic anemia, which affects both sexes with equal frequency. It occurs at any age and more frequently in Southeast Asian countries. It is the result of non malignant clonal expansion of hematopoietic progenitor cells. It is characterized by intravascular hemolytic anemia, recurrent thrombosis and a variable component of bone marrow failure. It is associated with other hematologic disorders such as aplastic anemia and myelodysplastic syndrome. Flow cytometry is the method of choice for diagnosis. Eculizumab and allogeneic bone marrow transplantation is the only effective therapies.

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.

Recurrent episodes of myoglobinuria, mental retardation and seizures but no hemolysis in two brothers with phosphoglycerate kinase deficiency.

We report two brothers with mild intellectual deficiency, exercise intolerance, rhabdomyolysis, seizures and no hemolysis. Phosphoglycerate kinase (PGK) activity was strongly decreased in their red blood cells. Subsequent molecular analysis of PGK1 revealed hemizygosity for a novel mutation c.756 + 3A > G, in intron 7. Analysis of the effect of this mutation on pre-mRNA processing demonstrated markedly decreased levels of normal PGK1 mRNA. In addition, the c.756 + 3A > G change resulted in abnormally spliced transcripts. If translated, these transcripts mostly encode for C-terminally truncated proteins. The consequences of the c.756 + 3A > G mutation is discussed, as well as the genotype-to-phenotype correlation with regard to previously described mutations (PGK Fukuroi and PGK Antwerp), which also result in C-terminal truncated proteins.

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.

Inicio, diagnóstico y seguimiento de un caso con deficiencia de acil-CoA deshidrogenasa de cadena muy larga / Debut, diagnosis and outcome of a case with very long chain acyl-CoA dehydrogenase deficiency

Los ácidos grasos representan el 80% de las necesidades energéticas en periodos de estrés metabólico. La betaoxidación de los ácidos grasos es catalizada por varias enzimas, como la acil-CoA deshidrogenasa-coenzima FAD, que posee 4 formas específicas según la longitud de la cadena de acil-CoA. La acil-CoA-deshidrogenasa de cadena muy larga es una de ellas. Su déficit cursa con la acumulación intramitocondrial de ésteres de acil-CoA de cadena larga, y afecta al corazón, el músculo esquelético y el hígado. Presentamos un caso iniciado a los 22 meses de edad con un síndrome Reye-like. Confirmamos un déficit de la betaoxidación de los ácidos grasos de cadena muy larga, con las mutaciones p.A232T (c.694G>A) y p.Y201C (c.602A>G) en los alelos del gen VLCAD. Describimos su evolución durante 17 años recibiendo una dieta pobre en ácidos grasos de cadena larga y suplementos con aceite MCT (AU)

Fatty acids represent 80% of energy needs during periods of stress. Beta-oxidation of fatty acids is catalyzed by some enzymes including acyl-CoA-dehydrogenase-coenzyme FAD, wich has four different ways according to the chain length of acyl-CoA. The very-long-chain-acyl-CoA-dehydrogenase is one of them. A deficiency of this enzyme produces an accumulation of long-chain-acyl-CoA-esters in mitochondrias, affecting heart, skeletal muscle and liver. We report the case of a 22-month aged child whose first symptom was a Reye-like syndrome. We confirmed that he was affected by a deficiency in the beta-oxidation of fatty acids of very long chain. He showed some mutations in the VLCAD gene alleles: p.A232T (c.694G>A) and p.Y201C (c.602A>G). We explain the evolution in the next 17 years, following a diet with very little long chain fatty acids and MCT oil supplements (AU)

Inhibition of cytochrome P450 2E1 and activation of transcription factor Nrf2 are renoprotective in myoglobinuric acute kidney injury.

Rhabdomyolysis accounts for ∼10% of acute kidney injuries. In glycerol-induced myoglobinuric acute kidney injury, we found an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear protein, a key redox-sensitive transcription factor, and Nrf2-regulated genes and proteins including upregulation of heme oxygenase-1. In in vitro studies, pretreatment of LLC-PK1 cells with an activator of Nrf2 before myoglobin exposure significantly decreased oxidant generation and cytotoxicity, whereas Nrf2 inhibition and gene silencing exacerbated the injury. Chlormethiazole, a specific CYP2E1 transcription inhibitor, prevented an increase in catalytic iron in the kidneys, decreased oxidative stress, blocked nuclear translocation of the Nrf2 protein, decreased heme oxygenase-1 upregulation, and provided functional and histological protection against acute kidney injury. CYP2E1 inhibitors and gene silencing in renal tubular epithelial cells significantly decreased reactive oxygen species generation and provided marked protection against myoglobin-induced cytotoxicity. Thus, during CYP2E1-induced oxidative stress, the transcription factor Nrf2 has a pivotal role in the early adaptive response. Inhibition of CYP2E1 coupled with the prior induction of Nrf2 may be a valuable tool to reduce CYP2E1-mediated rhabdomyolysis-induced acute kidney injury.

Novel mutations in myopathic form of carnitine palmitoyltransferase II deficiency in a Chinese patient.

BACKGROUND: Carnitine palmitoyltransferase II (CPT II) deficiency is one of the most common disorders of oxidative fatty acid metabolism. In this disorder, long-chain acylcarnitines cannot be converted to acyl CoA and there is impairment of ß-oxidation of fatty acids. RESULTS: In the 3 distinct clinical subtypes of CPT II deficiency, adult onset myopathic form shows mild clinical manifestations, characterized by recurrent rhabdomyolysis after intense physical stress. In this study, we report a case with adult myopathic form of CPT II deficiency presenting recurrent exercise-induced myoglobinuria. CONCLUSION: The acylcarnitine profile showed characteristic CPTII deficiency profile and sequencing of the CPT2 gene showed 2 novel missense mutations p. H369Q and p G497S.

Border-crossers' nephropathy: the risk of coming to America.

Immigrants attempting to cross the border often wander for days without food or water, subsequently developing acute kidney injury (AKI) secondary to rhabdomyolysis. In this article, we describe our experience with myoglobinuric AKI in these border crossers. Records from all patients in the custody of the border patrol from 1 June 2010 to 30 June 2011, who had AKI defined by the Acute Kidney Injury Network (AKIN) criteria and a CK > 1000 IU/L, were reviewed. The age, gender, temperature, days in the desert, initial serum creatinine, CK on presentation, need for dialysis, length of hospital stay, and serum creatinine at discharge were recorded and analyzed. Forty-two patients developed myoglobinuric AKI with a mean age of 32.5 years. Among them, 38 were males and four females. There was a mean of 4.2 days in the desert. Seven had stage 1 AKI, 10 stage 2, and 25 stage 3. 5 patients required hemodialysis. Only one patient had a temperature >100.6ºF on arrival. CKs ranged between 1101 and 447,966 IU/L. Mean length of stay was 4 days. Two patients were discharged on hemodialysis and eight were discharged with serum creatinine levels of  >1.3 mg/dL. This is the largest series of myoglobinuric AKI reported in border crossers. The kidney injury is presumably due to the excessive heat combined with volume depletion. We have coined the term "border crossers' nephropathy" for this disorder. This is a serious problem that has both political and economic consequences on both sides of the border.

Clinical features and new molecular findings in muscle phosphofructokinase deficiency (GSD type VII).

Muscle phosphofructokinase (PFKM) deficiency, a rare disorder of glycogen metabolism also known as glycogen storage disease type VII (GSDVII), is characterized by exercise intolerance, myalgias, cramps and episodic myoglobinuria associated with compensated hemolytic anaemia and hyperuricemia. We studied five patients with PFKM deficiency coming from different Italian regions. All probands showed exercise intolerance, hyperCKemia, cramps and myoglobinuria. One patient had a mild hypertrophic cardiomyopathy. Biochemical studies revealed residual PFK activity ranging from 1 to 5%. Molecular genetic analysis identified four novel mutations in the PFKM gene. In our series of patients, clinical and laboratory features were similar in all but one patient, who had an unusual phenotype characterized by 25 ears disease history, high CK levels, hypertrophic cardiomyopathy with paroxysmal atrial fibrillation without fixed muscle weakness.

High cut-off renal replacement therapy for removal of myoglobin in severe rhabdomyolysis and acute kidney injury: a case series.

BACKGROUND/AIM: Rhabdomyolysis is associated with the release of myoglobin into the circulation, promoting acute kidney injury (AKI). In severe rhabdomyolysis, dialysis-dependent AKI doubles mortality. Standard blood purification techniques have limited efficacy in removing myoglobin. We describe high cut-off (HCO) renal replacement therapy (RRT) as a novel approach for extracorporeal elimination of myoglobin in rhabdomyolysis-associated AKI. METHODS: With an in vivo molecular cut-off at 45 kDa, HCO filters are effective in removing myoglobin (17.8 kDa). Clearances across standard and HCO filters using continuous or intermittent RRT are reviewed in a case series of 11 patients with severe rhabdomyolysis and dialysis-dependent AKI. RESULTS: Median myoglobin clearance across standard high-flux filters was 3.3 (interquartile range 2.3-3.9) ml/min for sustained low-efficiency daily dialysis (SLEDD) batch hemodialysis (HD) and 3.7 (2.9-6.7) ml/min for conventional HD. Respective clearances using HCO filters (membrane surface area: 1.1 m(2)) were 21.7 (20.3-26.1) ml/min (SLEDD) and 44.2 (41.3-47.0) ml/min (HD). Corrected for filter size, up to 20-fold higher clearances were obtained using HCO filters, resulting in profound and sustained reduction of plasma myoglobin concentration. CONCLUSIONS: As a novel approach, HCO RRT allows for rapid and effective removal of myoglobin from the circulation. In light of the pathogenic role in AKI, reducing exposure of the kidney to myoglobin may improve renal recovery and patient outcome. Our data pave the way for prospective trials, addressing this issue.

Assessment of serum creatine kinase among adolescent patients following jimsonweed (Datura stramonium) and moonflower (Datura inoxia) ingestions: a review of 11 cases.

INTRODUCTION: Datura stramonium (DS) (jimsonweed) is well known for its abuse potential for hallucinogenic effects and Datura inoxia (DI) (moonflower) has been abused for similar effects. To our knowledge, only one case report describes rhabdomyolysis in association with DS or DI ingestion. CASE IDENTIFICATION AND DETAILS: Patient hospital charts were retrospectively screened from January 1, 2002 to December 31, 2007 to identify patients with qualifying ICD-9 codes for toxic plant ingestions. We report on 11 patient cases of DS/DI ingestions in which serum creatine kinase (CK) concentrations were monitored. These admissions occurred at our hospital over a 6-year period. Serum CK concentrations ranged from 72 to 70,230 U/L. Only three patients had serum CK concentrations greater than 1,000 U/L. One patient with a peak concentration of 70,230 U/L and a positive myoglobinuria was diagnosed with rhabdomyolysis. DISCUSSION: Based on our review of the literature and these cases, it is possible that serum CK concentrations may be elevated more frequently than previously realized. The clinical significance of this abnormal laboratory value is uncertain with the majority of patients remaining asymptomatic without any clinical evidence of rhabdomyolysis.