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

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Alexander Jerman ◽  
Milena Andonova ◽  
Vanja Peršič ◽  
Jakob Gubensek

Abstract 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.

2020 ◽  
Author(s):  
Omar maoujoud

Acute Kidney injury is relatively uncommon in COVID-19 patients yet carries a high mortality. It occurs in patients complicated with ARDS or multiorgan failure, but further investigation about inflammatory and apopotic mechanisms during renal impairment are needed. Since the development of AKI is an important negative prognostic indicator for survival with CoV as reported in previous SAR-CoV and MERS-CoV outbreaks, adequate medical management of high risk patients with AKI may improve the results of previous outbreaks related to CoV.


Author(s):  
Wenyan Liu ◽  
Yang Yan ◽  
Dan Han ◽  
Yongxin Li ◽  
Qian Wang ◽  
...  

Abstract Background Systemic inflammation contributes to cardiac surgery–associated acute kidney injury (AKI). Cardiomyocytes and other organs experience hypothermia and hypoxia during cardiopulmonary bypass (CPB), which induces the secretion of cold-inducible RNA-binding protein (CIRP). Extracellular CIRP may induce a proinflammatory response. Materials and Methods The serum CIRP levels in 76 patients before and after cardiac surgery were determined to analyze the correlation between CIRP levels and CPB time. The risk factors for AKI after cardiac surgery and the in-hospital outcomes were also analyzed. Results The difference in the levels of CIRP (ΔCIRP) after and before surgery in patients who experienced cardioplegic arrest (CA) was 26-fold higher than those who did not, and 2.7-fold of those who experienced CPB without CA. The ΔCIRP levels were positively correlated with CPB time (r = 0.574, p < 0.001) and cross-clamp time (r = 0.54, p < 0.001). Multivariable analysis indicated that ΔCIRP (odds ratio: 1.003; 95% confidence interval: 1.000–1.006; p = 0.027) was an independent risk factor for postoperative AKI. Patients who underwent aortic dissection surgery had higher levels of CIRP and higher incidence of AKI than other patients. The incidence of AKI and duration of mechanical ventilation in patients whose serum CIRP levels more than 405 pg/mL were significantly higher than those less than 405 pg/mL (65.8 vs. 42.1%, p = 0.038; 23.1 ± 18.2 vs. 13.8 ± 9.2 hours, p = 0.007). Conclusion A large amount of CIRP was released during cardiac surgery. The secreted CIRP was associated with the increased risk of AKI after cardiac surgery.


2020 ◽  
Vol 72 (1) ◽  
pp. 147-155 ◽  
Author(s):  
Ilona Nowak-Kózka ◽  
Kamil J. Polok ◽  
Jacek Górka ◽  
Jakub Fronczek ◽  
Anna Gielicz ◽  
...  

Abstract Background The effect of renal replacement therapy on drug concentrations in patients with sepsis has not been fully elucidated because the pharmacokinetic properties of many antimicrobials are influenced by both pathophysiological and treatment-related factors. The aim of this study was to determine meropenem concentrations in patients with sepsis before and after the initiation of continuous venovenous hemodialysis with regional citrate anticoagulation (RCA-CVVHD). Methods The study included 15 critically ill patients undergoing RCA-CVVHD due to sepsis-induced acute kidney injury. All participants received 2 g of meropenem every 8 h in a prolonged infusion lasting 3 h. Meropenem concentrations were measured in blood plasma using high-performance liquid chromatography coupled with tandem mass spectrometry. Blood samples were obtained at six-time points prior to and at six-time points after introducing RCA-CVVHD. Results The median APACHE IV and SOFA scores on admission were 118 points (interquartile range [IQR] 97–134 points) and 19.5 points (IQR 18–21 points), respectively. There were no significant differences in the plasma concentrations of meropenem measured directly before RCA-CVVHD and during the first 450 min of the procedure. The drug concentration reached its peak 2 h after initiating the infusion and then steadily declined. Conclusions The concentration of high-dose meropenem (2 g every 8 h) administered in a prolonged infusion was similar before and after the introduction of RCA-CVVHD in patients with sepsis who developed acute kidney injury.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Byeong Woo KIm ◽  
Sun hee Kim ◽  
Ki beom Bae

Abstract Background and Aims Although the mechanism of contrast-induced acute kidney injury (CI-AKI) is not fully known, the imbalance of vasoconstrictive and vasodilative mediators plays a major role. Prostaglandin E2 (PGE2) is one of the vasodilators involved in this process. Inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) causes elevation of PGE2 level in tissue by delaying the rapid degradation of PGE2 by the enzyme. We tested the hypothesis that the 15-PGE2 inhibitor would protect against CI-AKI in a mouse model and attempted to elucidate the mechanism involved. Method 10-week aged male C57/BL6 Mice were injected with 10gI/kg of iodixanol by tail vein. Renal blood flow measurement, right nephrectomy, and blood sampling were taken at 48 hours after iodixanol injection. The 15-PGDH inhibitor was injected before and after iodixanol administration. Plasma creatinine, NGAL, KIM-1 were measured as biomarkers for renal function. Histological evaluation was analyzed by the necrosis scoring system and TUNEL assay. Arteriolar area of outer medulla was analyzed by α-smooth muscle actin stain. Renal blood flow was measured by the non-invasive laser doppler. Results Plasma creatinine (1.94±0.75 vs 1.11±0.44 mg/dL, p=0.005), NGAL (299.7±115.87 vs 140.4±76.56 ng/mL, p=0.004), and KIM-1 (2.09±2.34 vs 0.43±0.89 ng/mL, p=0.024) levels were significantly lower when the 15-PGDH inhibitor was injected before and after iodixanol administration than the vehicle group. But no significant renal protective effect was shown when the 15-PGDH inhibitor was injected before or after iodixanol administration. The 15-PGDH inhibitor administration before and after iodixanol injection showed a significantly wider renal arteriolar area (683.63±248.46 vs 1132.97±357.46 μm2, p=0.039) and larger renal blood flow (360.0±49.72 vs 635.1±27.20, p=0.011) than vehicle administration. Conclusion The 15-PGDH inhibitor has a renal protective effect against CI-AKI in mice by increasing renal blood flow when injected intravenously before and after iodine contrast media administration.


2018 ◽  
Vol 6 (4) ◽  
pp. 323-335
Author(s):  
Peter Weighardt ◽  
Niels Hayashi

Sepsis is the leading cause of death in critically ill patients, and the incidence of sepsis is increasing causes multiorgan failure, including acute kidney injury (AKI) and patients with both sepsis and AKI have an especially high mortality rate. Several different pathophysiological mechanisms have been proposed for sepsis-induced AKI: vasodilation-induced glomerular hypoperfusion, dysregulated circulation within the peritubular capillary network, inflammatory reactions by systemic cytokine storm or local cytokine production, and tubular dysfunction induced by oxidative stress animal sepsis models have been developed using LPS infusion. Renal dysfunction evaluated by serum creatinine and BUN was found in acute non-survivors (<24 hours) and decreased urine output in subacute non-survivors (24–96 hours). The study show that increased AKI in animal with blood collected heparin (P=0.002) compared to citrate, furthermore; sham mice that received heparin did not develop AKI.


2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Yu-Zhen Han ◽  
Jin Zhang ◽  
Rong-Yue Gao ◽  
Song Zhao ◽  
Yue Zheng ◽  
...  

2020 ◽  
Vol 5 (1) ◽  
pp. 178-181
Author(s):  
Evi Lusiana ◽  
Nia Savitri Tamzil ◽  
Desi Oktarina

A B S T R A C TIntroduction. Acute kidney injury (AKI) is defined as sudden decline in theglomerular filtration rate, resulting in the retention of nitrogenous wastes, such asurea and creatinine in plasma. Cinnamomum burmannii is known as a anti-inflammatory renoprotective agent, although the precise mechanism is not wellunderstood. This study aimed to elucidate the effectiveness of Cinnamomumburmannii extract in decreasing creatinine level of acute kidney injury Ischemiareperfusion (IR) model. Method. We performed Ischemia reperfusion (IR) in maleWistar rat to induce acute kidney injury. The rat (n=30) were divided into six groups:IR, 1 group treated with methylprednisolone as a control (IR+M), 3 groups treatedwith different oral Cinnamomum burmannii extract doses (50mg/kg (IR+EKM1),100mg/kg (IR+EKM2), and 200 mg/kg (IR+EKM3), and a Sham operation (SO)group. AKI stage reduction based on serum creatinine levels, before and aftermodeling, before and after the cinnamon extract intervention. Creatinine levels werequntified by spectrophotometry and analyzed by SPSS. Result. Cinnamomumburmannii extract lowers creatinine levels; significant (P <0.05). 200 mg / kgbb isthe effective dose of lowering creatinine levels in the IR model. Conclusion.Cinnamomum burmannii extract reduced serum creatinine levels associated withdecreased acute renal staging in the IR model.


2021 ◽  
Author(s):  
Ying-yi Luan ◽  
En-ping Huang ◽  
Rong-ping Zhou ◽  
Jia-jia Huang ◽  
Zhen-jia Yang ◽  
...  

Abstract 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.


Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7589
Author(s):  
Jung-Yeon Kim ◽  
Hyo-Lim Hong ◽  
Gyun Moo Kim ◽  
Jaechan Leem ◽  
Hyun Hee Kwon

Septic acute kidney injury (AKI) is an important medical problem worldwide, but current treatments are limited. During sepsis, lipopolysaccharide (LPS) activates various signaling pathways involved in multiorgan failure. Carnosic acid is a natural phenolic diterpene and has multiple bioactivities, such as anti-tumor, anti-inflammatory, and anti-oxidative effects. However, the effect of carnosic acid on septic AKI has not been explored. Therefore, this study aimed to determine whether carnosic acid has a therapeutic effect on LPS-induced kidney injury. Administration of carnosic acid after LPS injection ameliorated histological abnormalities and renal dysfunction. Cytokine production, immune cell infiltration, and nuclear factor-κB activation after LPS injection were also alleviated by carnosic acid. The compound suppressed oxidative stress with the modulation of pro-oxidant and antioxidant enzymes. Tubular cell apoptosis and caspase-3 activation were also inhibited by carnosic acid. These data suggest that carnosic acid ameliorates LPS-induced AKI via inhibition of inflammation, oxidative stress, and apoptosis and could serve as a useful treatment agent for septic AKI.


Nephron ◽  
2020 ◽  
Vol 144 (12) ◽  
pp. 680-682
Author(s):  
Alexander L. Bullen ◽  
Joachim H. Ix

Tubular functions are critical for homeostasis maintenance. However, tubular function markers are not typically assessed in routine clinical care. Recent research by our group has revealed that tubular dysfunction at baseline is a risk factor for subsequent acute kidney injury (AKI), independent of estimated glomerular filtration rate and albuminuria. Here, we describe the underlying hypotheses and biological insights and contrast the changes in tubule function versus injury both before and after an AKI episode.


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