Continuous Venovenous Hemodiafiltration Versus Standard Medical Therapy for the Prevention of Rhabdomyolysis-Induced Acute Kidney Injury: A Retrospective Cohort Study

Aim: To determine whether continuous venovenous hemodiafiltration (CVVHDF) plus standard medical therapy (SMT) vs. SMT alone prevents rhabdomyolysis (RM)-induced acute kidney injury (AKI) and to analyze the related health economics.Methods: This retrospective cohort study involved patients with RM without AKI, coronary heart disease, or chronic kidney disease treated with CVVHDF plus SMT (treatment group, n = 9). Matched patients with RM without AKI treated with SMT only served as controls (1:1 ratio). Baseline characteristics, biochemical indexes, renal survival data, and health economic data were compared between groups. In the treatment group, some biochemical data were compared at different time points.Results: At 2 and 7 days after admission, serum biochemical indices (e.g., myoglobin, creatine kinase, creatinine, and blood urea nitrogen) did not differ between the two groups. Total (P = 0.011) and daily hospitalization costs (P = 0.002) were higher in the treatment group than in the control group. After 53 months of follow-up, no patient developed increased serum creatinine, except for 1 treatment-group patient who died of acute myocardial infarction. In the treatment group, myoglobin levels significantly differed before and after the first CVVHDF treatment (P = 0.008), and serum myoglobin, serum creatinine, and blood urea nitrogen decreased significantly at different time points after CVVHDF.Conclusions: Although CVVHDF facilitated myoglobin elimination, its addition to SMT did not improve serum myoglobin or other biochemical indices or the long-term renal prognosis. Despite similar hospitalization durations, both total and daily hospitalization costs were higher in the treatment group.

Serum Myoglobin Potentiates Acute Kidney Injury Following Exertional Heatstroke and Its Mechanisms Involved Endoplasmic Reticulum Stress-Associated Ferroptosis

Background: Myoglobin released by rhabdomyolysis (RM) is considered to be involved in the pathogenesis of kidney disease caused by crush injury, but whether a high level of serum myoglobin predisposes patients to acute kidney injury (AKI) and increases mortality following exertional heatstroke (EHS) and its molecular mechanisms are still unclear. Methods: Serum myoglobin concentrations in patients with EHS were measured at admission, 24 h and 48 h after admission and discharge. The risk of AKI at 48 hours was the primary outcome, AKI at discharge and death at 90 days were the secondary outcome. In experimental studies, we further investigated the mechanisms of human kidney proximal tubular (HK-2) cells that were exposed to human myoglobin under heat stress conditions and the effect of baicalein.Results: The myoglobin levels were assessed in 187 patients who were undergoing EHS, 82 who were undergoing AKI. The highest myoglobin quartile (vs. the lowest) had an adjusted odds ratio (OR) of 18.95 (95% confidence interval [CI], 6.00 to 59.83) for the primary outcome and the OR (vs. quartile 2) was 7.92 (95% CI, 1.62 to 38.89) for the secondary outcome. The survival rate of HK-2 cells treated with myoglobin under heat stress was significantly decreased, and the production of Fe2+ and ROS was markedly increased, accompanied by changes in ferroptosis proteins, including increased p53, decreased SLC7A11 and GPX4, and alterations in ERS marker proteins. Treatment with baicalein attenuated HK-2 cell ferroptosis induced by myoglobin under heat stress through inhibition of ERS. Conclusions: High serum myoglobin levels were associated with AKI and mortality following EHS, which mechanisms involved ferroptosis and ERS. Baicalein-targeted ERS- ferroptosis may be a potential therapeutic drug for the treatment of AKI in patients with RM after EHS.

MO668EXTRACORPOREAL REMOVAL OF MYOGLOBIN IN PATIENTS WITH RHABDOMYOLYSIS AND SEVERE ACUTE KIDNEY INJURY: COMPARISON OF HIGH AND MEDIUM CUT-OFF MEMBRANE AND AN ADSORBER CARTRIDGE

Background and Aims Severe rhabdomyolysis often causes acute kidney injury (AKI). If severe, AKI significantly reduces myoglobin removal through the kidneys. Given molecular size of myoglobin, extracorporeal removal using newer hemodialysis membranes and adsorption techniques is possible, although its role on clinically significant outcomes is not yet fully established. We aimed to compare the efficacy of high cut-off (HCO) membrane, medium cut-off (MCO) membrane and Cytosorb® adsorber on myoglobin removal. Method In this retrospective study we included 15 patients with AKI and concomitant rhabdomyolysis with severely increased myoglobin (>20.000 µg/L), who underwent at least one extracorporeal procedure with the intention of extracorporeal myoglobin removal. There were 28 procedures performed: 13 HCO (Theralite®, Gambro) dialysis, 9 MCO (Theranova®, Gambro) dialysis and 6 adsorber (Cytosorb®, Cytosorbents) procedures. Serum myoglobin and albumin levels were recorded from the time frame of up to 12 hours prior to and up to 12 hours after the index procedure and reduction rates (RR) for myoglobin were calculated. Albumin levels were compared before and after procedure as a safety parameter. Results Treatment duration differed significantly and was the longest for Cytosorb® adsorber (median 11 h) and the shortest for MCO membrane (median 5 h). Pre-treatment serum myoglobin levels were comparable across the groups. Reduction in myoglobin during procedure was significant for HCO and MCO and borderline significant in adsorber group, with respective median RR of 0.64, 0.54 and 0.50 (p = 0.83). Routine albumin substitution was implemented only in HCO group, but serum albumin levels were stable in all subgroups. Conclusion In this preliminary observational study we found comparable effectiveness of a novel MCO and ‘standard’ HCO dialysis membrane for serum myoglobin removal in patients with severe AKI. Cytokine adsorber showed borderline effectiveness, but the number of procedures in this group was small. MCO dialysis is associated with lower costs and no need for albumin supplementation and therefore might be the optimal mode of treatment of severe rhabdomyolysis-associated AKI. For patients with multiorgan failure requiring cytokine removal and severe myoglobinemia, hemoadsorption can reduce cytokine and myoglobin levels simultaneously.

Rhabdomyolysis is Associated with Hospital Mortality in Patients with COVID-19

Purpose: To evaluate the clinical features and outcomes of rhabdomyolysis (RM) in patients with COVID-19. Method: A single center retrospective cohort study of 1,014 consecutive hospitalized patients with confirmed COVID-19 at the Huoshenshan hospital in Wuhan, China, between February 17 and April 12, 2020. Results: The overall incidence of RM was 2.2%. Comparing with patients without RM, patients with RM tended to have a higher risk of deterioration, representing by higher ratio to be admitted to the intensive care unit (ICU) (90.9 % vs 5.3%, P<0.001), and to undergo mechanical ventilation (86.4 % vs 2.7% P<0.001). Compared with patients without RM, patients with RM had laboratory test abnormalities, including indicators of inflammation, coagulation activation and kidney injury. Patients with RM had a higher risk of hospital death (P < 0.001). Cox proportional hazard regression model confirmed that RM indicators, including peak creatine kinase (CK) >1000 IU/L (HR=6.46, 95% CI: 3.02-13.86), peak serum myoglobin (MYO) >1000 ng/mL (HR=9.85, 95% CI: 5.04-19.28) were independent risk factors for in-hospital death. Additionally, patients with COVID-19 that developed RM tended to have a delayed virus clearance.Conclusion: RM might be an important factor contributing to adverse outcomes of patients with COVID-19. Early detection and effective intervention of RM may help reduce deaths of patients with COVID-19.

Effects of Extended Lower Extremity Cooling Following Zone 3 REBOA in a Porcine Hemorrhage Model

Introduction External cooling of ischemic limbs has been shown to have a significant protective benefit for durations up to 4 hours. Materials and Methods It was hypothesized that this benefit could be extended to 8 hours. Six swine were anesthetized and instrumented, then underwent a 25% total blood volume hemorrhage. Animals were randomized to hypothermia or normothermia followed by 8 hours of Zone 3 resuscitative endovascular balloon occlusion of the aorta, then resuscitation with shed blood, warming, and 3 hours of critical care. Physiologic parameters were continuously recorded, and laboratory specimens were obtained at regular intervals. Results There were no significant differences between groups at baseline. There were no significant differences between creatine kinase in the hypothermia group when compared to the normothermia group (median [IQR] = 15,206 U/mL [12,476−19,987] vs 23,027 U/mL [18,745−26,843]); P = 0.13) at the end of the study. Similarly, serum myoglobin was also not significantly different in the hypothermia group after 8 hours (7,345 ng/mL [5,082−10,732] vs 5,126 ng/mL [4,720−5,298]; P = 0.28). No histologic differences were observed in hind limb skeletal muscle. Conclusion While external cooling during prolonged Zone 3 resuscitative endovascular balloon occlusion of the aorta appears to decrease ischemic muscle injury, this benefit appears to be time dependent. As the ischemic time approaches 8 hours, the benefit from hypothermia decreases.

THE APPLICATION OF MAGNETIC RESONANCE IMAGING FOR DIAGNOSTICS OF ACUTE POSTEXERCISE RHABDOMYOLYSIS

Introduction. Rhabdomyolysis is destruction syndrome of striated skeletal muscle characterized by myalgia, an increase of creatine phosphokinase level (CPK), serum myoglobin and myoglobulinuria. This review presents the analysis of five cases of acute postexercise rhabdomyolysis happened to militaries, complicated by pigmentary nephropathy with the description of clinical and laboratory studies, magnetic resonance imaging (MRI), electroneuromyographic and morphological features. The purpose of the study is the clinical assessment of MRI for the diagnosis of postexercise rhabdomyolysis. Results. A comparative assessment demonstrated that in the presented clinical cases in the muscle groups with minimal edematous changes, an increase in the MR signal was observed at T2-WISPAIR, as well as in diffusion-weighted images (factor b — 0, 500, 1000), at the same time on all other pulse sequences (including STIR) changes in signal intensity were not detected. Conclusion. There was shown that in mild cases of rhabdomyolysis, the regression of MR manifestations corresponds to a decrease in laboratory parameters of CPK and myoglobin, whereas in severe forms of rhabdomyolysis, the regression of MR manifestations is significantly slowed down relative to laboratory indicators, and in the place of necrosis areas, the foci of degeneration form (hyperintensive on T1 and T2-WI, hypo-intensive on T1-WI-SPIR and T2-WI-SPAIR). Morphologically confirmed the fact of pronounced hemorrhage in the compartment syndrome due to postload rhabdomyolysis (hyperintensive sites on T1-WI and T1-WI-SPIR, iso-, hypointensive on T2-WI, T2-WI-SPAIR).