Telbivudine-induced rhabdomyolysis in a patient undergoing haemodialysis: A case report and review of literature.

Herein, we describe a case of acute rhabdomyolysis in a man in his early 50s undergoing haemodialysis and receiving the antiviral drug, telbivudine, for chronic hepatitis B virus (HBV) infection. Following diagnosis by electromyography (EMG), magnetic resonance image (MRI) scans and laboratory data (i.e., elevated serum creatinine kinase (CK) and myoglobin) telbivudine was discontinued and the patient was treated with methylprednisolone. While his CK and myoglobin levels decreased rapidly, his muscle weakness and pain improved slowly. Learning points include: patients undergoing haemodialysis and concomitantly receiving antiviral treatment for HBV, should have their serum levels of CK and myoglobin monitored regularly; treatment with corticosteroids maybe required; relief from rhabdomyolysis-induced muscle weakness and pain may be slow due to nerve fibre damage.

Protective effect of citronellol in rhabdomyolysis-induced acute kidney injury in mice.

Acute kidney injury (AKI) is a serious pathophysiological event consequent to rhabdomyolysis. Inflammatory mechanisms play a role in the development of rhabdomyolysis-induced AKI. Citronellol (CT) is a naturally occurring monoterpene in essential oils of aromatic plant species. In this study, we explored the protective effects of citronellol on AKI resulting from glycerol-induced rhabdomyolysis. Rhabdomyolysis was induced by a single intramuscular injection of glycerol 50% (10mg/kg) in the thigh caudal muscle. Four groups of mice were assigned, including a control group, a group administered with glycerol to induce AKI as a model, a group treated with glycerol plus 50mg/kg CT, and a group treated with glycerol plus 100mg/kg CT. The renal function of mice from all groups was evaluated using kidney histopathological changes and kidney injury molecule-1 (KIM-1). Myoglobin levels were measured to detect rhabdomyolysis. Apoptosis was evaluated by renal cleaved caspase-3 and BAX levels. Both doses of citronellol (50mg/kg and 100mg/kg) significantly reduced KIM-1 mRNA expression and myoglobin levels compared to the glycerol group. In addition, citronellol resulted in lower cleaved caspase-3 and BAX in the renal tissue, indicating that citronellol exerted an anti-apoptotic effect in AKI. Citronellol showed a reno-protective effect against rhabdomyolysis-induced AKI, which may be attributed to its anti-apoptotic effects.

Dietary docosahexaenoic acid plays an opposed role in ferroptotic and non-ferroptotic acute kidney injury.

Ferroptosis due to polyunsaturated fatty acid (PUFA) peroxidation has been implicated in the pathogenesis of acute kidney injury (AKI), suggesting the risk of dietary intake of PUFA for people susceptible to AKI. Clinically, however, in addition to ferroptosis, other mechanisms also contribute to different types of AKI such as inflammation associated necroptosis and pyroptosis. Therefore, the role of PUFA, especially ω3 PUFA which is a common food supplement, in various AKIs deserves further evaluation. In this study, rhabdomyolysis- and folic acid-induced AKI (Rha-AKI and FA-AKI) were established in mice fed with different fatty acids Histology of kidney, blood urea nitrogen and creatinine, lipid peroxidation, and inflammatory factors were examined. Results showed that these two types of AKIs had diametrically different pathogenesis indicated by that ferrostatin-1 (Fer-1), a lipid antioxidant, can attenuate FA-AKI rather than Rha-AKI. Further, dietary DHA (provided by fish oil) reduced tubular injury and renal lesion by inhibiting peroxidation and inflammation in mice with Rha-AKI while increasing cell death, tissue damage, peroxidation and inflammation in mice with FA-AKI. In human renal tubular epithelial cell line HK-2, MTT assay and DHE staining showed that both myoglobin and ferroptosis inducers can cause cell death and oxidative stress. Ferroptosis inducer-induced cell death was promoted by DHA, while such result was not observed in myoglobin-induced cell death when adding DHA. This study illustrates that the mechanisms of AKI might be either ferroptosis dependent or -independent and the deterioration effect of dietary DHA depends on whether ferroptosis is involved.

Post-injury Inhibition of Endothelin-1 Dependent Renal Vasoregulation Mitigates Rhabdomyolysis-Induced Acute Kidney Injury.

In patients with rhabdomyolysis, the overwhelming release of myoglobin into the circulation is the primary cause of kidney injury. Myoglobin causes direct kidney injury as well as severe renal vasoconstriction. An increase in renal vascular resistance (RVR) results in renal blood flow (RBF) and glomerular filtration rate (GFR) reduction, tubular injury, and acute kidney injury (AKI). The mechanisms that underlie rhabdomyolysis-induced AKI are not fully understood but may involve the local production of vasoactive mediators in the kidney. Studies have shown that myoglobin stimulates endothelin-1 (ET-1) production in glomerular mesangial cells. Circulating ET-1 is also increased in rats subjected to glycerol-induced rhabdomyolysis. However, the upstream mechanisms of ET-1 production and downstream effectors of ET-1 actions in rhabdomyolysis-induced AKI remain unclear. Vasoactive ET-1 is generated by ET converting enzyme 1 (ECE-1)-induced proteolytic processing of inactive big ET to biologically active peptides. The downstream ion channel effectors of ET-1-induced vasoregulation include the transient receptor potential cation channel, subfamily C member 3 (TRPC3). This study demonstrates that glycerol-induced rhabdomyolysis in Wistar rats promotes ECE-1-dependent ET-1 production, RVR increase, GFR decrease, and AKI. Rhabdomyolysis-induced increases in RVR and AKI in the rats were attenuated by post-injury pharmacological inhibition of ECE-1, ET receptors, and TRPC3 channels. CRISPR/Cas9-mediated knockout of TRPC3 channels attenuated ET-1-induced renal vascular reactivity and rhabdomyolysis-induced AKI. These findings suggest that ECE-1-driven ET-1 production and downstream activation of TRPC3-dependent renal vasoconstriction contribute to rhabdomyolysis-induced AKI. Hence, post-injury inhibition of ET-1-mediated renal vasoregulation may provide therapeutic targets for rhabdomyolysis-induced AKI.

Heme Proteins and Kidney Injury: Beyond Rhabdomyolysis.

Heme proteins, the stuff of life, represent an ingenious biologic strategy that capitalizes on the biochemical versatility of heme, and yet is one that avoids the inherent risks to cellular vitality posed by unfettered and promiscuously reactive heme. Heme proteins, however, may be a double-edged sword because they can damage the kidney in certain settings. Although such injury is often viewed mainly within the context of rhabdomyolysis and the nephrotoxicity of myoglobin, an increasing literature now attests to the fact that involvement of heme proteins in renal injury ranges well beyond the confines of this single disease (and its analog, hemolysis); indeed, through the release of the defining heme motif, destabilization of intracellular heme proteins may be a common pathway for acute kidney injury, in general, and irrespective of the underlying insult. This brief review outlines current understanding regarding processes underlying such heme protein-induced acute kidney injury (AKI) and chronic kidney disease (CKD). Topics covered include, among others, the basis for renal injury after the exposure of the kidney to and its incorporation of myoglobin and hemoglobin; auto-oxidation of myoglobin and hemoglobin; destabilization of heme proteins and the release of heme; heme/iron/oxidant pathways of renal injury; generation of reactive oxygen species and reactive nitrogen species by NOX, iNOS, and myeloperoxidase; and the role of circulating cell-free hemoglobin in AKI and CKD. Also covered are the characteristics of the kidney that render this organ uniquely vulnerable to injury after myolysis and hemolysis, and pathobiologic effects emanating from free, labile heme. Mechanisms that defend against the toxicity of heme proteins are discussed, and the review concludes by outlining the therapeutic strategies that have arisen from current understanding of mechanisms of renal injury caused by heme proteins and how such mechanisms may be interrupted.

Blood purification with a cytokine adsorber for the elimination of myoglobin in critically ill patients with severe rhabdomyolysis.

BACKGROUND: Rhabdomyolysis is frequently occurring in critically ill patients, resulting in a high risk of acute kidney injury (AKI) and potentially permanent kidney damage due to increased myoglobin levels. The extracorporeal elimination of myoglobin might be an approach to prevent AKI, but its molecular weight of 17 kDa complicates an elimination with conventional dialysis membranes. Question of interest is, if myoglobin can be successfully eliminated with the cytokine adsorber Cytosorb® (CS) integrated in a high-flux dialysis system. METHODS: Patients were included between 10/2014 and 05/2020 in the study population if they had an anuric renal failure with the need of renal replacement therapy, if CS therapy was longer than 90 min and if myoglobin level was > 5.000 ng/ml before treatment. The measurement times of the laboratory values were: d-1 = 24-36 h before CS, d0 = shortly before starting CS and d1 = 12-24 h after starting CS treatment. Statistical analysis were performed with Spearman's correlation coefficient, Wilcoxon test with associated samples and linear regression analysis. RESULTS: Forty-three patients were included in the evaluation (median age: 56 years, 77% male patients, 32.6% ECMO therapy, median SAPS II: 80 points and in-hospital mortality: 67%). There was a significant equilateral correlation between creatine kinase (CK) and myoglobin at all measurement points. Furthermore, there was a significant reduction of myoglobin (p = 0.03, 95% confidence interval (CI): - 9030, - 908 ng/ml) during CS treatment, with a median relative reduction of 29%. A higher median reduction of 38% was seen in patients without ongoing rhabdomyolysis (CK decreased during CS treatment, n = 21). In contrast, myoglobin levels did not relevantly change in patients with increasing CK and therefore ongoing rhabdomyolysis (n = 22, median relative reduction 4%). Moreover, there was no significant difference in myoglobin elimination in patients with and without ECMO therapy. CONCLUSION: Blood purification with Cytosorb® during high-flux dialysis led to a significant reduction of myoglobin in patients with severe rhabdomyolysis. The effect might be obscured by sustained rhabdomyolysis, which was seen in patients with rising CK during treatment. Prospective clinical trials would be useful in investigating its benefits in avoiding permanent kidney damage.

Prevención de FRA asociado a depósitos intratubulares de origen endógeno: rabdomiólisis, mieloma múltiple y síndrome de lisis tumoral / Prevention of ARF associated to endogen intra-tubular deposits: rhabdomyolysis, multiple myeloma, and tumor lysis syndrome

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Visual color and doneness indicators and the incidence of premature brown color in beef patties cooked to four end point temperatures.

An interlaboratory study was undertaken to assess the frequency that cooked color of ground beef patties appeared brown at internal temperatures of 52.7 degrees C (135 degrees F), 65.6 degrees C (150 degrees F), 71.1 degrees C (160 degrees F), and 79.4 degrees C (175 degrees F). In general, as internal cooked temperature of the patties increased, the following results were observed in the patties: (i) more brown meat color, (ii) less pink or red juice color, and (iii) more cooked texture. However, brown meat color occurred prematurely at the two lower internal temperatures (57.2 degrees C/135 degrees F and 65.6 degrees C/150 degrees F) that are insufficient to eliminate foodborne pathogens without holding times. The common consumer practice of freezing bulk ground beef, followed by overnight thawing in a refrigerator, led to substantial premature brown color in patties cooked from this product. In addition, at 71.1 degrees C (160 degrees F), recognized to be the lowest temperature for cooking ground beef safely in the home, meat color, juice color, and texture appearance were not fully apparent as doneness indicators. In fact, at no temperature studied did 100% of the patties appear done when evaluated by the criteria of no red or pink in the meat, no red or pink in the juices, or by texture appearance. Patties in this study were evaluated under a set protocol for forming the products, cooking, and viewing under the same lighting conditions. Other preparation conditions are possible and may produce different results. Thus, temperature to which patties have been cooked cannot be judged by color and appearance. This study provided the evidence to support the message to consumers regarding cooking of beef patties of "use an accurate food thermometer and cook beef patties to 160 degrees F (71.1 degrees C)" in place of messages based on consumer judgment of cooked color.