Cause Of Severe Rhabdomyolysis Research Articles

Systemic corticosteroids for the treatment of acute episodes of rhabdomyolysis in lipin-1-deficient patients.

Mutations in the LPIN1 gene constitute a major cause of severe rhabdomyolysis (RM). The TLR9 activation prompted us to treat patients with corticosteroids in acute conditions. In patients with LPIN1 mutations, RM and at-risk situations that can trigger RM have been treated in a uniform manner. Since 2015, these patients have also received intravenous corticosteroids. We retrospectively compared data on hospital stays by corticosteroid-treated patients vs. patients not treated with corticosteroids. Nineteen patients were hospitalized. The median number of admissions per patient was 21 overall and did not differ when comparing the 10 corticosteroid-treated patients with the 9 patients not treated with corticosteroids. Four patients in the non-corticosteroid group died during a RM (mean age at death: 5.6 years). There were no deaths in the corticosteroid group. The two groups did not differ significantly in the number of RM episodes. However, for the six patients who had RM and occasionally been treated with corticosteroids, the median number of RM episodes was significantly lower when intravenous steroids had been administered. The peak plasma creatine kinase level and the area under the curve were or tended to be higher in patients treated with corticosteroids-even after the exclusion of deceased patients or focusing on the period after 2015. The median length of stay (10 days overall) was significantly longer for corticosteroid-treated patients but was similar after the exclusion of deceased patients. The absence of deaths and the higher severity of RM observed among corticosteroid-treated patients could suggest that corticotherapy is associated with greater survival.

Bee stings an unusual cause of severe rhabdomyolysis: A case report and literature review

Wasp and bee stings are common among the rural population of Sri Lanka. It is known to cause local reaction and rarely anaphylaxis. Bee sting associated rhabdomyolysis leading to acute kidney injury (AKI) is a rare complication and was not reported from Northern Sri Lanka. This case report illustrates a patient who developed rhabdomyolysis following multiple bee stings and made a complete clinical recovery with prompt and optimal supportive care.

An Observational Epidemiological Study of Exercise-induced Rhabdomyolysis Causing Acute Kidney Injury: A Single-center Experience.

Exercise-induced rhabdomyolysis (EIR) is an uncommon cause of severe rhabdomyolysis and a very rare cause of acute kidney injury (AKI). A prospective observational study of 25 patients diagnosed with EIR was conducted in a multispecialty hospital in Dubai, from 2009 to 2015. Five out of 25 patients experienced AKI necessitating temporary renal replacement therapy. The initial presentation, biochemical parameters, and clinical course of patients were monitored, to understand epidemiology and risk factors for the development of AKI. There was male preponderance (4 out of 5 patients), higher rate of systemic symptoms (all 5 patients) versus 60% in NRAKI), oligo-anuria (all 5 patients), compartment syndrome (3 out \\of 5) and severe dehydration seen in patients with RAKI group. On laboratory evaluation, there was higher rise in creatinine kinase (CK) enzyme, serum and urine myoglobin levels impaired renal function on presentation, hyperuricemia, high D-dimer level, PCV of more than 55%, found to be associated with RAKI as compared to NRAKI group. Hematuria by positive urine dipstick with absent red blood cells on urinalysis, is an insensitive tool as was present in only 62% and 43% of RAKI and NRAKI groups, respectively. It was also observed that delayed pesentation for medical care, metabolic acidosis, were commonly associated with AKI. All patients with RAKI required RRT for a comparable period of time (3–4 weeks). In all of them, no deterioration or relapse reported on follow-up of 3 months.

Molecular analysis of LPIN1 in Jordanian patients with rhabdomyolysis

Recessive mutations in LPIN1, which encodes a phosphatidate phosphatase enzyme, are a frequent cause of severe rhabdomyolysis in childhood. Hence, we sequenced the 19 coding exons of the gene in eight patients with recurrent hereditary myoglobinuria from four unrelated families in Jordan. The long-term goal is to facilitate molecular genetic diagnosis without the need for invasive procedures such as muscle biopsies. Three different mutations were detected, including the novel missense mutation c.2395G>C (Gly799Arg), which was found in two families. The two other mutations, c.2174G>A (Arg725His) and c.1162C>T (Arg388X), have been previously identified, and were found to cosegregate with the disease phenotype in the other two families. Intriguingly, patients homozygous for Arg725His were also homozygous for the c.1828C>T (Pro610Ser) polymorphism, and were exercise-intolerant between myoglobinuria episodes. Notably, patients homozygous for Arg388X were also homozygous for the c.2250G>C silent variant (Gly750Gly). Taken together, the data provide family-based evidence linking hereditary myoglobinuria to pathogenic variations in the C-terminal lipin domain of the enzyme. This finding highlights the functional significance of this domain in the absence of structural information. This is the first analysis of LPIN1 in myoglobinuria patients of Jordanian origin, and the fourth such analysis worldwide.

Study of LPIN1, LPIN2 and LPIN3 in rhabdomyolysis and exercise‐induced myalgia

Recessive LPIN1 mutations were identified as a cause of severe rhabdomyolysis in pediatric patients. The human lipin family includes two other closely related members, lipin-2 and 3, which share strong homology and similar activity. The study aimed to determine the involvement of the LPIN family genes in a cohort of pediatric and adult patients (n = 171) presenting with muscular symptoms, ranging from severe (CK >10 000 UI/L) or moderate (CK <10 000 UI/L) rhabdomyolysis (n = 141) to exercise-induced myalgia (n = 30), and to report the clinical findings in patients harboring mutations. Coding regions of LPIN1, LPIN2 and LPIN3 genes were sequenced using genomic or complementary DNAs. Eighteen patients harbored two LPIN1 mutations, including a frequent intragenic deletion. All presented with severe episodes of rhabdomyolysis, starting before age 6 years except two (8 and 42 years). Few patients also suffered from permanent muscle symptoms, including the eldest ones (≥ 40 years). Around 3/4 of muscle biopsies showed accumulation of lipid droplets. At least 40% of heterozygous relatives presented muscular myalgia. Nine heterozygous SNPs in LPIN family genes were identified in milder phenotypes (mild rhabdomyolysis or myalgia). These variants were non-functional in yeast complementation assay based on respiratory activity, except the LPIN3-P24L variant. LPIN1-related myolysis constitutes a major cause of early-onset rhabdomyolysis and occasionally in adults. Heterozygous LPIN1 mutations may cause mild muscular symptoms. No major defects of LPIN2 or LPIN3 genes were associated with muscular manifestations.

Pemetrexed as a possible cause of severe rhabdomyolysis in the treatment of lung cancer

According to many published clinical trials, both haematological and non-haematological toxicities resulting from pemetrexed were relatively mild and therefore this drug is considered to be well tolerated. We came across a 60 y/o woman patient with stage IV adenocarcinoma, suffered from unexpected life threatening complication, rhabdomyolysis. Severe lower leg weakness and respiratory failure occurred on the day 3 after pemetrexed administration. To the best of our knowledge, this is the first report that addresses severe and life-threatening rhabdomyolysis which occur during chemotherapy for the treatment of lung cancer.We believed pemetrexed is a safe drug but we should pay attention to possible complications related to pemetrexed-based treatment and to also treat the life-threatening disorder of rhabdomyolysis immediately to prevent further damage.

LPIN1 gene mutations: a major cause of severe rhabdomyolysis in early childhood

Autosomal recessive LPIN1 mutations have been recently described as a novel cause of rhabdomyolysis in a few families. The purpose of the study was to evaluate the prevalence of LPIN1 mutations in patients exhibiting severe episodes of rhabdomyolysis in infancy. After exclusion of primary fatty acid oxidation disorders, LPIN1 coding sequence was determined in genomic DNA and cDNA. Among the 29 patients studied, 17 (59%) carried recessive nonsense or frameshift mutations, or a large scale intragenic deletion. In these 17 patients, episodes of rhabdomyolysis occurred at a mean age of 21 months. Secondary defect of mitochondrial fatty oxidation or respiratory chain was found in skeletal muscle of two patients. The intragenic deletion, c.2295-866_2410-30del, was identified in 8/17 patients (47%), all Caucasians, and occurred on the background of a common haplotype, suggesting a founder effect. This deleted human LPIN1 form was unable to complement Delta pah1 yeast for growth on glycerol, in contrast to normal LPIN1. Since more than 50% of our series harboured LPIN1 mutations, LPIN1 should be regarded as a major cause of severe myoglobinuria in early childhood. The high frequency of the intragenic LPIN1 deletion should provide a valuable criterion for fast diagnosis, prior to muscle biopsy.

Acute renal failure due to severe rhabdomyolysis: a rare clinical manifestation of atrial myxoma

Rhabdomyolysis is usually caused by physical, infectious or toxic factors and may be complicated by acute renal failure (ARF) associated with a high mortality rate of more than 20% [1]. We report about a very unusual, but emergent cause of severe rhabdomyolysis due to peripheral embolism of a left atrial myxoma. A 36-year-old male patient was admitted to hospital due to lumbalgia. Patient’s history revealed neither traumatic injury nor intake of drugs. Clinical examination only showed right-sided weakness in ankle dorsiflexion, hip flexion and adduction. Vital parameters, ECG findings, X-ray and MRI of the lumbar spine were normal. Laboratory tests revealed highly elevated serum creatine phosphokinase (286,580 U/l, n: ≤270 U/l), myoglobin (56,000 μg/l, n: ≤75 μg/l), lactate dehydrogenase (4,926 U/l, n: ≤232 U/l), aspartate aminotransferase (4,263 U/l, n: ≤35 U/l), alanine aminotransferase (701 U/l, n: ≤45 U/l) levels and inflammation parameters (CRP 145 mg/l, n: ≤8 mg/l). Renal function was impaired (creatinine 173 μmol/l, n: 61–104 μmol/l; urea-N 5 mmol/l, n: 1.3–3.5 mmol/l; uric acid 655 μmol/l, n: 208–440 μmol/l; glomerular filtration rate 31 ml/min, n: 80–170 ml/min/1.73 m2). Kidney ultrasonography revealed no signs of hydronephrosis or perfusion defects. MRI of pelvis and thighs due to the development of acute myalgias in the right leg demonstrated compartment syndrome of the M. iliopsoas and femoral muscles. After emergent fasciotomy, transthoracic echocardiography performed due to hemodynamic instability demonstrated a left atrial inhomogenous mass (Fig. 1a). Furthermore, MRI angiography initiated due to signs of lower extremity vascular occlusion revealed a circumscribed perfusion defect at the aortic bifurcation (Fig. 1b). Surgical removal of the atrial mass and its aortic embolus was immediately performed and histopathology revealed a typical cardiac myxoma (Fig. 1c). Patient’s postoperative course was complicated by ARF, arrhythmias and serious infections. However, multiple organ dysfunction could completely be restored after 6 weeks of intensive care management. Fig. 1 Embolism of a left atrial cardiac myxoma a Echocardiography. Four-chamber image from ECG-gated line-balanced fast field echo pulse sequence showed an intra-atrial mass (arrow) with attachment to the inter-atrial septum. LA left atrial cavity, LV left ...

Relationship between elevated creatine phosphokinase and the clinical spectrum of rhabdomyolysis.

The incidence, causes and complications of severe rhabdomyolysis (creatine phosphokinase (CK) > or = 5000 U/l) were studied during a 7-year study period in a large university hospital population. This condition was present in 0.074% of all admitted patients. The mortality in the study group (n = 93) was 32% and the incidence of acute renal failure (ARF) 51%. Ischaemia was the most frequent cause, and drugs, alcohol and/or coma were the second most common cause of severe rhabdomyolysis. Patients with rhabdomyolysis due to ischaemia were older, had ARF more often, and also had the highest mortality. Hyperkalaemia (potassium > or = 5.5 mmol/l) occurred in 13% of the patients, and all of them had or developed an impaired renal function. Hypocalcaemia (calcium < or = 2.00 mmol/l) was found in 41%. The incidence of ARF and electrolyte disturbances was higher in patients with CK levels exceeding 15,000 U/l. Mortality was significantly higher in patients with ARF. Plasma concentrations of potassium and calcium correlated better with the severity of renal failure than with the maximal height of plasma CK.