Rhabdomyolysis Group Research Articles

Proteomic analysis of multiple organ dysfunction induced by rhabdomyolysis

Rhabdomyolysis (RM) leads to dysfunction in the core organs of kidney, lung and heart, which is an important reason for the high mortality and disability rate of this disease. However, there is a lack of systematic research on the characteristics of rhabdomyolysis-induced injury in various organs and the underlying pathogenetic mechanisms, and especially the interaction between organs. We established a rhabdomyolysis model, observed the structural and functional changes in kidney, heart, and lung. It is observed that rhabdomyolysis results in significant damage in kidney, lung and heart of rats, among which the pathological damage of kidney and lung was significant, and of heart was relatively light. Meanwhile, we analyzed the differentially expressed proteins (DEPs) in the kidney, heart and lung between the RM group and the sham group based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). In our study, Serpina3n was significantly up-regulated in the kidney, heart and lung. Serpina3n is a secreted protein and specifically inhibits a variety of proteases and participates in multiple physiological processes such as complement activation, inflammatory responses, apoptosis pathways, and extracellular matrix metabolism. It is inferred that Serpina3n may play an important role in multiple organ damage caused by rhabdomyolysis and could be used as a potential biomarker. This study comprehensively describes the functional and structural changes of kidney, heart and lung in rats after rhabdomyolysis, analyzes the DEPs of kidney, heart and lung, and determines the key role of Serpina3n in multiple organ injury caused by rhabdomyolysis. SignificanceThis study comprehensively describes the functional and structural changes of kidney, heart and lung in rats after rhabdomyolysis, analyzes the DEPs of kidney, heart and lung, and determines the key role of Serpina3n in multiple organ injury caused by rhabdomyolysis.

Protective role of alpha-lipoic acid against rhabdomyolysis-induced acute kidney injury in rats.

Rhabdomyolysis, a potentially life-threatening condition, occurs when myoglobin is released from damaged muscle cells, leading to acute kidney injury (AKI). Alpha lipoic acid (ALA), an organosulfur compound known for its anti-oxidant and anti-inflammatory properties, was examined in this study for its potential impact on rhabdomyolysis-induced AKI in rats. Six groups of rats were included in the study, with each group consisting of six rats (n=6): Control, rhabdomyolysis, rhabdomyolysis treated with different doses of ALA (5, 10, and 20 mg/kg), and ALA alone (20 mg/kg) groups. Rhabdomyolysis was induced by intramuscular injection of glycerol on the first day of the experiment, while ALA was administered intraperitoneally for four consecutive days. Renal function parameters, oxidative stress markers, and histological changes in the kidneys were evaluated. Western blot analysis was performed to measure the levels of neutrophil gelatinase-associated lipocalin (NGAL) and tumor necrosis factor-alpha (TNF-α) proteins. A significant increase in serum urea, creatinine, renal malondialdehyde, NGAl, and TNF-α protein levels was observed in glycerol-injected rats. In addition, a significant decrease in glutathione was recorded. Compared to the rhabdomyolysis group, treatment with ALA recovered kidney histological and biochemical abnormalities. Results suggest that rhabdomyolysis-induced AKI is associated with increased oxidative stress and inflammation. Treatment with ALA improved kidney histological abnormalities and reduced oxidative stress markers in rats. Therefore, ALA may have a potential protective effect against rhabdomyolysis-induced AKI.

Clinical features of snake envenomation in South Korea

Introduction Three venomous snakes of the Gloydius genus belonging to the Viperidae family cause most snake envenomations in South Korea. Envenomation signs often include local swelling, coagulopathy, and rhabdomyolysis. The benefit of additional antivenom after the initial does is unclear. Methods This retrospective study divided patients into four groups according to the presence of rhabdomyolysis (creatine kinase ≥1000 IU/L) and coagulopathy, which were defined using the Korean Society on Thrombosis and Hemostasis disseminated intravascular coagulation score (rhabdomyolysis, coagulopathy, combination, and local effects groups). We describe the clinical features of envenomation and the antivenom response. Results Greater local swelling predicted more severe snakebite pain. Ninety of the 231 enrolled patients (38.9%) developed rhabdomyolysis. The patients with severe rhabdomyolysis in the combination group displayed higher peak creatine kinase activity than the rhabdomyolysis group. Seven patients with rhabdomyolysis, including two patients requiring kidney replacement therapy, developed acute kidney injury, but the incidence of acute kidney injury did not differ between the combination group and rhabdomyolysis group. Bleeding developed in 3.5% of the patients, but its incidence did not differ between the combination and coagulopathy groups. Approximately half of all patients needed repeated antivenom administration, mainly due to the local envenomation effect. Earlier administration of additional antivenom for progressive local swelling did not reduce the hospitalization duration. Conclusion Rhabdomyolysis is one of the major effects of Gloydius snake envenomation in South Korea, although it is not associated with the same risk of clinical deterioration as coagulopathy. Additionally, the ability of antivenom to ameliorate local swelling should be investigated to prevent unnecessary antivenom administration in South Korea.

Rhabdomyolysis induced by venomous snake bite

Purpose: Despite previous studies reporting the development of rhabdomyolysis (RM), this affliction tends to be neglected as an envenomation sign in South Korea. The current retrospective study investigates the prevalence and prognosis of RM after a snakebite. We further searched for predictors of snakebite-induced RM, which can be observed at presentation. Methods: This study included 231 patients who presented to the ED within 24 hours after a snakebite. The patients were classified according to the severity of RM, and the data, comprising baseline characteristics and clinical course including the level of creatine kinase (CK), were collected and compared according to the severity of RM. Results: The prevalence of RM and severe RM were determined to be 39% and 18.5%, respectively. Compared to the group without RM or with mild RM, the group with severe RM had a higher grade of local swelling, a higher frequency of acute kidney injury and neurotoxicity, and a greater need for renal replacement therapy and vasopressor administration. However, the incidence of acute renal injury in the RM group was 7.7%, with two patients needing renal replacement therapy. No mortalities were reported at discharge. Results of the multinomial logistic regression model revealed that the WBC levels are significantly associated with the risk of severe RM. Conclusion: RM should be considered the primary clinical sign of snake envenomation in South Korea, although it does not seem to worsen the clinical course. In particular, physicians should pay attention to patients who present with leukocytosis after a snakebite, which indicates the risk of developing RM, regardless of the CK level at presentation.

Angiotensin 1–7 mitigates rhabdomyolysis induced renal injury in rats via modulation of TLR-4/NF-kB/iNOS and Nrf-2/heme‑oxygenase-1 signaling pathways

AimsRhabdomyolysis (RM) is a critical condition with a high mortality rate, but effective management is still deficient. Till date, there are no studies that have addressed the effect of angiotensin 1–7 in this condition, hence, the rationale of this study was to evaluate the potential protective effect of Angiotensin 1–7 (Ang1–7), on rhabdomyolysis (RM) induced kidney injury in rats and detecting the underlying mechanistic insights. Main methodsForty adult male albino rats were divided into groups; the control group, RM group, RM+Ang1-7 group, and RM+Ang1-7+ A779 group. Sera and urine samples were collected for analysis of renal and muscle injury markers. Kidney tissues were taken for estimation of oxidative, inflammatory, and apoptotic markers as well as angiotensin-II (Ang II) and Ang1–7. Renal histology and expression of inducible nitric oxide synthase-1 (iNOS), real-time PCR for angiotensin-converting enzyme-2 (ACE-2), nuclear erythroid factor-2 (Nrf-2), Toll like receptor 4 (TLR-4) and NF-kB in kidney tissues were also measured. Key findingsInduction of RM caused renal oxidative stress injury, inflammation, apoptosis and marked deterioration in kidney functions as well as reduction of Ang1–7 and raised Angiotensin-II level in kidney tissues. Administration of Ang1–7 to the RM group reversed all the affected parameters which were blocked by A779 administration (Mas receptor blocker). SignificanceWe concluded that Ang1–7 could be a potential therapeutic agent that could mitigate RM-induced renal injury. The underlying mechanisms may involve Stimulation of the ACE-2/Ang1–7/MasR axis and modulation of TLR-4/NF-kB/iNOS and Nrf-2/heme‑oxygenase -1 pathways.

Nigella sativa and its main constituent, thymoquinone protect against glycerol-induced acute kidney injury in rats.

Rhabdomyolysis is a life-threatening disease caused by releasing myoglobin from injured myocytes, which results in acute kidney injury. In this study, the effect of aqueous-alcoholic extract of Nigella sativa (NS) and thymoquinone (TQ) on rhabdomyolysis-induced kidney damage in rats was investigated. There were five groups of rats (n=8): Control, rhabdomyolysis, rhabdomyolysis treated with NS aqueous-alcoholic extract (200 and 400 mg/kg) and TQ (15 mg/kg). Treatments were given for 7 days (two days before and four days after glycerol injection). Glycerol was injected intramuscularly on the third day of the experiment for induction of rhabdomyolysis. Renal function parameters on the first, fourth, and seventh days of the experiment and renal oxidative stress and histological changes at the end of this study were assessed. Glycerol injection caused a significant increase in serum level of urea, creatinine, creatine phosphokinase, urine output and tissue MDA compared to the control animals (p<0.05-0.001). Administration of NS extract and TQ significantly decreased serum urea and creatinine on days 4 and 7, creatine phosphokinase on day 4, and urine output on day 7 compared to the rhabdomyolysis group (p<0.05-0.001). Compared to the rhabdomyolysis group, treatment with NS extract and TQ improved kidney histological abnormalities (p<0.01-0.001). The catalase enzyme activity in the group treated with NS 400 mg/kg and thiol content in the NS 400 mg/kg and TQ groups were significantly higher than those of the rhabdomyolysis group (p<0.05-0.01). NS extract and to some extent TQ protect the kidney from rhabdomyolysis-induced injury.

Incidence, Risk Factors, and Outcomes of Rhabdomyolysis in Hospitalized Patients With COVID-19 Infection.

Introduction: There is a paucity of studies examining the prevalence and clinical characteristics of rhabdomyolysis in hospitalized patients with COVID-19 infection. The purpose of this study is to examine the incidence, clinical characteristics, and outcome of hospitalized patients with COVID-19 infection who develop rhabdomyolysis.Methodology: This is a single-center retrospective analysis of all hospitalized patients with COVID-19 admitted between March 8, 2020, and January 11, 2021. All patients with creatinine kinase (CK) levels available during the hospital admission were included. Rhabdomyolysis was defined as an elevation in CK level higher than five times the upper limit of normal (i.e., 1125 U/L). We compared clinical characteristics and outcomes of patients who developed rhabdomyolysis with patients who did not develop rhabdomyolysis.Results: The incidence of rhabdomyolysis in hospitalized patients with COVID-19 infection was 9.2%. There was no significant difference noted in comorbidities and clinical characteristics between the two groups. Moreover, there was no significant difference noted in the presence of severe COVID-19 infection (72.7% vs 54.6%, p = 0.1), mortality (27.3% vs 23.9%, p = 0.72), acute kidney injury (59.1% vs 42.7%, p = 0.14), or need for intensive care unit (ICU) care (72.7% vs 51.4%, p = 0.051). However, a higher percentage of patients in the rhabdomyolysis group required physical rehabilitation after discharge (40.9% vs 19.3%, p = 0.02).Conclusion: The overall incidence of rhabdomyolysis in hospitalized patients with COVID-19 infection was high (9.2%). The presence of rhabdomyolysis was not associated with the increased severity of the disease. Patients with rhabdomyolysis more frequently required physical rehabilitation compared to those without rhabdomyolysis.

Relationship between creatine kinase and liver enzymes in war wounded with rhabdomyolysis

BackgroundRhabdomyolysis is a frequent complication in war wounded. Its complex pathophysiology suggests that it not only affects kidneys but also other organs such as the liver. The aim of this study was to evaluate the relationship between creatine kinase (CK) and liver enzymes in war wounded with rhabdomyolysis. MethodsWar wounded admitted to the intensive care unit of Percy Military Hospital between 2009 and 2017 with a rhabdomyolysis (CK peak >1,000 U/L) were included. They were divided in two groups: mild (CK peak <10,000 U/L) and severe rhabdomyolysis (CK peak ≥10,000 U/L). Demographic characteristics, peaks in transaminases, alkaline phosphatase (ALP), bilirubin, and CK were recorded. Mann Whitney-U test and, Fisher's exact test were used as appropriate. A Pearson's correlation test was used to determine the correlation between CK and liver enzymes after a log-normal transformation of the data. ResultsFifty-one patients were included (31 in the mild and 20 in the severe rhabdomyolysis group). Patients in the severe rhabdomyolysis group were more likely victims of explosions (85% vs 39%, p = 0.003). The transaminases peak was significantly higher in the severe rhabdomyolysis group (median AST peak 398 (270–944) vs 91 (63–157) U/L, p <0.0001, and median ALT peak 106 (77–235) vs 45 (34–71) U/L, p<0.0001). Bilirubin and ALP were higher in the severe rhabdomyolysis group (39 (25–49) vs 14(11–23) U/L, p = 0.0031 and 84 (55–170) vs 52 (39–85) U/L, p = 0.0063, respectively). We found a significant positive linear correlation between CK and ALT (r = 0.73, p<0.0001), AST (r = 0.89, p<0.0001), ALP (r = 0.41, p = 0.0035), and bilirubin (r = 0.37, p = 0.0083). ConclusionWe found a statistically significant positive correlation between CK and liver enzymes in rhabdomyolysis war wounded, indicating that hepatic damage occurs when rhabdomyolysis is severe and associated with elevated bilirubin and ALP. Further studies are needed to confirm this phenomenon and elucidate the pathophysiological mechanism. Level of evidenceIV Study TypeDiagnostic

Exogenous Biological Renal Support Improves Kidney Function in Mice With Rhabdomyolysis-Induced Acute Kidney Injury.

Background: Rhabdomyolysis (RM) is a clinical syndrome characterized by breakdown of skeletal muscle fibers and release of their contents into the circulation. Myoglobin-induced acute kidney injury (AKI) is one of the most severe complications of RM. Based on our previous research, exogenous biological renal support alleviates renal ischemia–reperfusion injury in elderly mice. This study aimed to determine whether exogenous biological renal support promotes renal recovery from RM-induced AKI and to preliminarily explore the mechanisms involved.Methods: A parabiosis animal model was established to investigate the effects of exogenous biological renal support on RM-induced AKI. Mice were divided into three groups: the control group (in which mice were injected with sterile saline), the RM group (in which mice were injected with 8 mL/kg glycerol), and the parabiosis + RM group (in which recipient mice were injected with glycerol 3 weeks after parabiosis model establishment). Blood samples and kidney tissue were collected for further processing 48 h after RM induction. Bioinformatics analysis was conducted via Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, functional enrichment analysis, and clustering analysis.Results: No mice died within 48 h after the procedure. Exogenous biological renal support attenuated the histological and functional deterioration in mice with RM-induced AKI. Bioinformatics analysis identified key pathways and proteins involved in this process. We further demonstrated that exogenous biological renal support ameliorated AKI through multiple mechanisms, including by suppressing the complement system; attenuating oxidative stress, inflammation, and cell death; and increasing proliferation.Conclusions: Exogenous biological renal support provided by parabiosis can improve renal function in RM-induced AKI by suppressing the complement system; decreasing oxidative stress, inflammation, and cell death; and promoting tubular cell proliferation. Our study provides basic research evidence for the use of bioartificial kidneys to treat RM-induced AKI.

Association of D-dimer and acute kidney injury associated with rhabdomyolysis in patients with exertional heatstroke: an over 10-year intensive care survey

Patients with rhabdomyolysis (RM) following exertional heatstroke (EHS) are often accompanied by dysfunction of coagulation and acute kidney injury (AKI). The purpose of this study was to investigate the relationship between D-dimer and AKI in patients with RM following EHS. A retrospective study was performed on patients with EHS admitted to the intensive care unit over 10-year. Data including baseline clinical information at admission, vital organ dysfunction, and 90-day mortality were collected. A total of 84 patients were finally included, of whom 41 (48.8%) had AKI. AKI patients had more severe organ injury and higher 90-day mortality (34.1 vs.0.0%, p < 0.001) than non-AKI patients. Multivariate logistic analysis showed that D-dimer (OR 1.3, 95% CI 1.1–1.7, p = 0.018) was an independent risk factor for AKI with RM following EHS. Curve fitting showed a curve relationship between D-dimer and AKI. Two-piecewise linear regression showed that D-dimer was associated with AKI in all populations (OR 1.3, 95% CI 1.2–1.5, p < 0.001) when D-dimer <10.0 mg/L, in RM group (OR 1.3, 95% CI 1.1–1.5, p < 0.001) when D-dimer >0.4 mg/L, in the non-RM group (OR 6.4, 95% CI 1.7–23.9, p = 0.005) when D-dimer <1.3 mg/L and D-dimer did not increase the incidence of AKI in the non-RM group when D-dimer >1.3 mg/L. AKI is a life-threatening complication of RM following EHS. D-dimer is associated with AKI in critically ill patients with EHS. The relationship between D-dimer and AKI depends on whether RM is present or not.

Are we ignoring coexisting rhabdomyolysis as an important aggravating factor for acute kidney injury among childhood diabetic ketoacidosis?

Although Acute Kidney Injury (AKI) has been described among childhood diabetes ketocidosis (cDKA) there is scarcity of literature on the role of concomitant rhabdomyolysis. A retrospective chart review was undertaken (2014-2018) to identify cDKA who developed AKI and had evidence of rhabdomyolysis defined by serum creatine phosphokinase (CPK)>5 times upper limit of normal. 46 cDKA were identified. Ten (22%) developed AKIwith 6/10 reaching peak AKI Stage 3 and 8/10 had co-current rhabdomyolysis. In comparison to non rhabdomyolysis group, cDKA with rhabdomyolysis were at presentationsignificantly more likely to be hypotensive and have higher corrected sodium and calculated osmolality. Subsequently they were more likely to develop lower trough potassium levels during treatment. Five patients, all with rhabdomyolysis, needed dialysis: median duration 9days (range 4-35). Three children in our cohort died, all from infection complications during treatment, one in AKI only group who did not receive dialysis and two in AKI with rhabdomyolysis on dialysis. Rhabdomyolysis was common among our cohort of cDKA with AKI and was associated with high morbidity and mortality. Rapid flux in electrolytes and osmolality may be important precipitating factors. We recommend larger prospective studies exploring the importance of rhabdomyolysis among cDKA with AKI.

Retrospective analysis of diabetic hyperosmolar hyperglycemia complicated with rhabdomyolysis

Objective To investigate the clinical characteristics and treatment strategies of diabetic hyperosmolar hyperglycemia (HHS) with rhabdomyolysis (RM). Methods The clinical data of 40 patients with HHS treated in the General Hospital of Shenyang Military Command from November 2013 to November 2017 were retrospectively analyzed.According to the serum levels of creatine phosphokinase and myoglobin, they were divided into RM group (12 cases) and non-RM group (28 cases). The clinical characteristics and treatment results of the two groups were compared. Results There were 12 cases in the RM group, 6 cases were diagnosed RM at the time of consultation, and 6 cases developed RM during the course of treatment.Compared with the non-RM group, RM group had lower systolic pressure[(98.3±17.8)mmHg vs.(128.0±18.1)mmHg, t=4.823, P=0.000], higher blood glucose level[(44.4±14.0)mmol/L vs.(32.6±8.1)mmol/L, t=2.717, P=0.016], and more acidosis, mainly manifested by lower pH[(7.16±0.15)vs.(7.32±0.13), t=3.355, P=0.002], lower bicarbonate[(12.92±5.23)mmol/L vs.(19.07±6.80)mmol/L, t=2.792, P=0.008], higher blood D-3 hydroxybutyric acid [(5.84±2.98)mmol/L vs.(2.55±2.13)mmol/L, t=4.012, P=0.000], and renal function was worse[creatinine (257.1±149.8)μmol/L vs.(148.1±85.3)μmol/L, t=2.925, P=0.006]. Individualized rehydration and low dose insulin were given to control blood sugar, and increasing blood pressure, kidney protection, correction of electrolyte disturbance, anti-infection and inhibition of gland secretion were given to the complications.Hydration and alkalization were given to 7 cases of RM, and continuous renal replacement therapy (CRRT) was given to 5 cases.In 10 cases of HHS with RM, creatine kinase decreased, renal function recovered, and 2 patients died. Conclusion It is very important to improve the understanding of RM in HHS patients, routinely monitor the dynamic changes of muscle enzymes, make a good early diagnosis and prevention of RM.Urine hydration and alkalization should be given in time after RM occurs, and CRRT treatment as early as possible can improve the survival rate of diabetic patients. Key words: Diabetes mellitus; Hyperglycemic hyperosmolar nonketotic coma; Diabetic ketoacidosis; Rhabdomyolysis; Creatine kinase; Myoglobin; Acute kidney injury; Rehydration solutions; Renal replacement therapy; Retrospective studies

SUN-173 COMPARISON BETWEEN RHABDOMYOLYSIS INDUCED AND SEPTIC ACUTE KIDNEY INJURY

Acute kidney injury (AKI) is one of the most serious complications of rhabdomyolysis (RM). AKI occurs in 13 to 50% of all cases of rhabdomyolysis, where mortality rates might rise up to 59% in critically ill patients. We studied the etiologies, severity, biochemical changes, clinical course and prognosis of rhabdomyolysis induced AKI (RM-AKI) and compared it with septic AKI among hospitalized patients. A prospective study with comparison between AKI secondary to rhabdomyolysis and sepsis was conducted in a tertiary hospital in central Nepal. AKI was diagnosed as per KDIGO guidelines. Rhabdomyolysis was diagnosed if serum creatinine phosphokinase (CK) raised more than five times the upper limit of normal level and sepsis as an increase of two or more points in the SOFA score with the evidence of infection. Simple descriptive analysis was performed to compare the outcome between two groups. A total of 145 patients with AKI (21 with RM and 124 with sepsis) were included in the study. Mean age of the patients was 43.7 years and majority (54.5%) aged between 30 to 49 years. Fifty-four percentage of patients were males. Wasp bite and bee sting combined together (47.6%) were the most common causes for RM-AKI whereas pneumonia accounted for 46.6% of the septic AKI. Among patients with RM-AKI, mean level of CK was 31644 mcg/L at presentation and 148.5 mcg/L at discharge. Serum creatinine (sCr) at admission and at discharge were 3.8 and 1.4 mg/dL respectively in RM-AKI group; and 2.4 and 1.6 mg/dL in septic AKI group. Stage 3 AKI was seen 52.4% in RM group and 33.9% in septic AKI group with indication of hemodialysis for 28.6% and 21.8% of patients in two groups respectively. Duration of stays in the hospital (9.2 versus 6.4 days) and ICU (4.2 versus 3.7 days) were longer in RM than in septic AKI. In hospital mortality was 4.8% in RM and 8.9% in septic AKI. Achievement of complete recovery, defined as the latest sCr returned to normal range (<1.2 mg/dL) or within 20% of baseline sCR, was better in septic AKI (51.6% versus 47.6%). This first ever study done in Nepal has found that, despite a longer duration of hospital stay, RM-AKI had a lower in-hospital mortality than septic AKI.

Transaminase and Creatine Kinase Ratios for Differentiating Delayed Acetaminophen Overdose from Rhabdomyolysis.

IntroductionRhabdomyolysis and delayed acetaminophen hepatotoxicity may be associated with elevated serum transaminase values. Establishing the cause of elevated transaminases may be especially difficult because of limited or inaccurate histories of acetaminophen ingestion. We hypothesized that the comparative ratios of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) can differentiate acetaminophen hepatotoxicity from rhabdomyolysis.MethodsA retrospective chart review of patients in four hospitals from 2006 to 2011 with a discharge diagnosis of acetaminophen toxicity or rhabdomyolysis was performed. Subjects were classified into three groups: rhabdomyolysis, acetaminophen overdose (all), and acetaminophen overdose with undetectable serum acetaminophen concentrations [acetaminophen(delayed)]. Ratios of AST, ALT, and CK were compared using non-parametric statistical methods.Results1,353 subjects were identified and after applying our exclusion criteria there were 160 in the rhabdomyolysis group, 68 in the acetaminophen overdose (all) group, and 29 in the acetaminophen (delayed) group. The AST/ALT ratio for the rhabdomyolysis group was 1.66 (Interquartile range: 1.18–2.22), for the acetaminophen overdose (all) group was 1.38 (1.08–1.69, statistically lower than the rhabdomyolysis group, p = 0.018), and for the acetaminophen (delayed)group was 1.30 (1.06–1.63, p = 0.037). CK/AST ratios were 21.3 (12.8–42.2), 5.49 (2.52–15.1, p < 0.001), and 3.80 (1.43–13.8, p < 0.001) respectively. CK/ALT ratios were 37.1 (16.1–80.0), 5.77 (2.79–25.2, p < 0.001), and 5.03 (2.20–17.4, p < 0.001) respectively. Increasing CK to transaminase ratio cutoffs resulted in increasing test sensitivity but lower specificity.ConclusionAST/ALT, CK/AST and CK/ALT ratios are significantly larger in rhabdomyolysis when compared to patients with acetaminophen toxicity. This result suggests that the ratios could be used to identify patients with rhabdomyolysis who otherwise might have been diagnosed as delayed acetaminophen toxicity. Such patients may not require treatment with N-acetylcysteine, resulting in cost savings and improved resource utilization.

Role of the Serum Muscular Enzymes in the Diagnosis of Post-Exertional Rhabdomyolysis in Draft Horses Used in Transplant Rice Seedlings

The present study was done to evaluate the role of serum muscular enzymes in the determination of the workload in healthy horses, and diagnosis of rhabdomyolysis (ER) cases. Twenty-one draft horses were assessed under the field conditions during rice seedling seasons. Animals were under complete history, physical examination and laboratory evaluation of serum muscular enzymes. Horses were categorized into 2 main groups; the first group, healthy horses under rice seedling work (n=10). They were examined and sampled 4times/day work. The second group includes horses with exertional rhabdomyolysis under rice seedlings workload (n=11) and they were examined and sampled on admission. Blood samples were collected and as a minimum, serum creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were evaluated. The obtained results clarified significant alterations in the vital signs in the exertional rhabdomyolysis group in comparison to healthy horses under the same workload in the four examination periods. Additionally, highly significant increase (P ≤0.001) in serum CK, LDH and AST levels in exertional rhabdomyolysis cases in comparison to the healthy horses and to the normal reference limits. While two or more folds increase in the serum muscular enzymes were recorded in healthy horses during workload and 4 h post-work when compared to the pre-work measurements. This, in turn, reflects the great load in healthy horses during rice seedling seasons.

Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats.

Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects.

Postoperative rhabdomyolysis following robotic renal and adrenal surgery: a cautionary tale of compounding risk factors.

This study aimed at reviewing a contemporary series of patients who underwent robotic renal and adrenal surgery by a single surgeon at a tertiary referral academic medical center over a 6-year period, specifically focusing on the unique and serious complication of post-operative rhabdomyolysis of the dependent lower extremity. The cases of 315 consecutive patients who underwent robotic upper tract surgery over a 6-year period from August 2008 to June 2014 using a standardized patient positioning were reviewed and analyzed for patient characteristics and surgical variables that may be associated with the development of post-operative rhabdomyolysis. The incidence of post-operative rhabdomyolysis in our series was 3/315 (0.95%). All three affected patients had undergone robotic nephroureterectomy. Those patients who developed rhabdomyolysis had significantly higher mean Body Mass Index, Charlson Comorbidity Index, and median length of stay than those who did not. The mean OR time in the rhabdomyolysis group was noted to be 52 min longer than the non-rhabdomyolysis group, though this value did not reach statistical significance. Given the trends of increasing obesity in the United States and abroad as well as the continued rise in robotic upper tract urologic surgeries, urologists need to be increasingly vigilant for recognizing the risk factors and early treatment of the unique complication of post-operative rhabdomyolysis.

Perspective on Rhabdomyolysis-Induced Acute Kidney Injury and New Treatment Options

Aim: The purpose of this study was to assess the role of caspase-dependent apoptosis, caspase 1, calpain 1, inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) and the protective effect of grape seed proanthocyanidin extract (GSPE) in the development of rhabdomyolysis-induced acute kidney injury (AKI). Materials and Methods: Twenty-one rats were divided into 3 groups - control, rhabdomyolysis and rhabdomyolysis + GSPE. Rhabdomyolysis was induced in the rhabdomyolysis and rhabdomyolysis + GSPE groups with the injection into both hind limbs of 10 ml/kg hypertonic (50%) glycerol following 24-hour dehydration on the 6th day. The rhabdomyolysis + GSPE group was given GSPE at 100 mg/kg by gavage for 7 days. The experiment was concluded 48 h after glycerol injection. Blood specimens were collected, and kidney tissues were extracted for histopathological examination. Results: We identified an increase in blood urea nitrogen, creatinine, histopathological score, iNOS, caspase 3, caspase 1 and calpain 1 expression in the rhabdomyolysis group compared to the controls and a decrease in eNOS expression. In the rhabdomyolysis + GSPE group, however, there was a decrease in these mediators, together with an increase in eNOS expression. Conclusion: This study shows for the first time in the literature that calpain 1 is involved in the pathogenesis of rhabdomyolysis-induced AKI, and that GSPE may have a renoprotective effect.

Reply to the Letter of Stroh et al. Regarding the Manuscript “Rhabdomyolysis After Bariatric Surgery by Roux-en-Y-Gastric Bypass: a Prospective Study” by Oliveira et al.

Dear Editor, We appreciate the interest of Stroh and colleagues in our work. This letter is an additional evidence of growing interest in neuromuscular and other neurological complications of bariatric surgery (BS). A few years ago, when we became interested in this subject, it was possible to find just a few articles, especially case reports, related to this issue. Fortunately, in the last years, there are more and more prospective and review studies of neurological complications of BS [1–5]. The comments about anesthetic agents and their potential risk of inducing myopathy and rhabdomyolysis (RML) are pertinent. During our research, we were concerned about this issue: the agents used in our patients were midazolam, rocuronium, fentanyl, and isoflurane, without use of propofol. Moreover, none of our patients were in use of statin or another potential myotoxic drug. We would like to clarify that we did not affirm that RML has higher frequency in females. As a matter of fact, we stated that “In our series, gender was not a risk factor of occurrence of RML” [6]. Furthermore, we also wrote that “In the prospective study of Carvalho et al. (30), and many case reports (11, 19–28), RML has been more commonly seen in men.” Although we found a higher absolute number of females in our series (63.6%) and even in the RML group (ten females and seven males), the difference failed to reach statistical significance (p=0.61, Fischer’s test). Regarding Table 3, we apologize for the error about the gender of the patients in four studies therein mentioned (Collier et al.[7], Pasnik et al.[8], Stroh et al. [9], VillalobosTorres et al. [10]), since the correct gender was male. On the other hand, Stroh et al. made two minor mistakes in their letter since the authors were Collier et al., instead of Coller et al., and they mentioned the study by Forrestire et al. [11], a study which is not present in our Table. In Table 4, the item gender (women in%) means, as discussed in the text, the gender distribution in the studies, with no mention of RML. Regarding comorbidities, the statistical analysis comparing the group with and without RML did not show statistical significance, considering that they were found in 12 of 17 patients in the RML group and three of five patients in the group without RML (p=1.00, Fisher’s test). Although the available knowledge about mechanism of RML after BS suggests a relationship between comorbidities and RML, the lack of significant correlation in our study may result from the small number of patients because the total number of individuals with comorbidities was 15 and the number in the group without RML was only three. Finally, the statement “RML after RYGBD bariatric surgery is a common complication” is appropriate, considering its high frequency in our study. We must bear in mind, however, that our investigation was not a comparative study of types of surgery. Incidentally, RYGBP often involves many of the risk factors described by Stroh et al., such as operation time>4 h, BMI>50 Kg/m, and some comorbidities. In some prospective studies involving different types of BS, as in Mognol et al. [12] and Lagandre et al.[13], the frequency of RML was much higher in F. Cardoso : L. D. Oliveira Neurology Service, Internal Medicine Department, The Federal University of Minas Gerais, Belo Horizonte, Minas Gerias, Brazil

Bacterial sepsis-induced rhabdomyolysis.

To describe the syndrome of rhabdomyolysis during bacterial sepsis with regard to incidence, blood bacteriology and complications and to examine the association between hyperosmolal state and rhabdomyolysis, evaluating the relationship between plasma osmolality (Posm) and serum creatine phosphokinase (CPK) levels. Prospective study including all patients admitted to the intensive care unit (ICU) for sepsis with positive blood culture and rhabdomyolysis over a 3-year period. Seven-bed medical/surgical ICU of a teaching hospital. 35 patients (group 1) with bacterial sepsis-induced rhabdomyolysis (15 males, 20 females; mean age 71+/-13 years) and 122 (group 2) bacteraemic septic patients without rhabdomyolysis (49 males, 73 females; mean age 68+/-15) were studied. Patients with rhabdomyolysis were divided into gram(+) and gram(-) subgroups according to the blood culture growth. From 491 patients recorded, 35 fulfilled the inclusion criteria for bacterial sepsis-induced rhabdomyolysis (7.1%). Gram-positive bacteria predominated in group 1 (69%), while gram-negative predominated (60%) in group 2. There was a correlation between CPK and Posm levels in the rhabdomyolysis Group (r = 0.52, R2 = 0.27, p = 0.003). There was a stronger correlation between these two variables (r = 0.67, R2 = 0.45, p = 0.001) in the gram(+).subgroup. Acute renal failure (68.5%) and electrolyte disorders such as hyperkalaemia (34%) and hypocalcaemia (48.5%) were the major complications in the rhabdomyolysis group. Sixteen (45.7%) patients in group 1 and 49 (40%) in group 2 died during their stay in the ICU from sepsis and multiple organ failure. Rhabdomyolysis was not considered a contributing factor to their death, as none of our patients died during or immediately after the syndrome. Bacterial sepsis-induced rhabdomyolysis results from certain types of microorganisms, mainly gram-positive and to a lesser extent gram-negative. Hyperosmolality is a predisposing mechanism for rhabdomyolysis during bacteraemic sepsis from any type of bacterial microorganism.