Dataset Information

Recombinant antithrombin attenuates acute kidney injury associated with rhabdomyolysis: an in vivo animal study.

ABSTRACT:

Background

Rhabdomyolysis is characterized by the destruction and necrosis of skeletal muscle tissue, resulting in acute kidney injury (AKI). Recombinant antithrombin (rAT) has DNA repair and vascular endothelial-protection properties. Herein, we investigated whether rAT therapy has beneficial effects against rhabdomyolysis-induced AKI. Ten-week-old male B6 mice were injected with 5 mL/kg of 50% glycerol intramuscularly in the left thigh after 24 h of fasting to create a rhabdomyolysis mouse model. Further, 750 IU/kg rAT was injected intraperitoneally at 24 and 72 h after the rhabdomyolysis model was established. The mice were euthanized after 96 h for histological analysis. Saline was administered to mice in the control group.

Results

Blood tests show elevated serum creatinine, urea nitrogen, and neutrophil gelatinase-associated lipocalin levels in rhabdomyolysis. Loss of tubular epithelial cell nuclei and destruction of the tubular luminal surface structure was observed in the untreated group, which improved with rAT treatment. Immunostaining for Ki-67 showed increased Ki-67-positive nuclei in the tubular epithelial cells in the rAT group, suggesting that rAT may promote tubular epithelial cell regeneration. The microvilli of the brush border of the renal tubules were shed during rhabdomyolysis, and rAT treatment reduced this injury. The vascular endothelial glycocalyx, which is usually impaired by rhabdomyolysis, became functional following rAT treatment.

Conclusions

Treatment with rAT suppressed rhabdomyolysis-induced AKI, suggesting that rAT therapy may be a novel therapeutic approach.

SUBMITTER: Miura T

PROVIDER: S-EPMC10822833 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Recombinant antithrombin attenuates acute kidney injury associated with rhabdomyolysis: an in vivo animal study.

Miura Tomotaka T Okuda Tomoki T Suzuki Kodai K Okada Hideshi H Tomita Hiroyuki H Takada Chihiro C Mori Kosuke K Asano Hirotaka H Kano Soichiro S Wakayama Yugo Y Fukuda Yohei Y Fukuda Hirotsugu H Nishio Ayane A Kawasaki Yuki Y Kuroda Ayumi A Suzuki Keiko K Kamidani Ryo R Okamoto Haruka H Fukuta Tetsuya T Kitagawa Yuichiro Y Miyake Takahito T Nakane Keita K Suzuki Akio A Yoshida Takahiro T Tetsuka Nobuyuki N Yoshida Shozo S Koie Takuya T Ogura Shinji S

Intensive care medicine experimental 20240129 1

<h4>Background</h4>Rhabdomyolysis is characterized by the destruction and necrosis of skeletal muscle tissue, resulting in acute kidney injury (AKI). Recombinant antithrombin (rAT) has DNA repair and vascular endothelial-protection properties. Herein, we investigated whether rAT therapy has beneficial effects against rhabdomyolysis-induced AKI. Ten-week-old male B6 mice were injected with 5 mL/kg of 50% glycerol intramuscularly in the left thigh after 24 h of fasting to create a rhabdomyolysis m ...[more]

PMID: 38282162

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Project description:ImportanceAn association between serum creatine kinase (CK) levels and the risk of kidney failure in patients with exertional rhabdomyolysis (ERM) has been suggested. However, the actual incidence of AKI in hospitalized patients with ERM along with the contributing cofactors that may increase the risk of AKI have rarely been investigated.ObjectivesTo examine the incidence of kidney injury in hospitalized patients with ERM and to identify additional cofactors that might contribute to the development of kidney injury in patients with ERM.Design, setting, and participantsThis retrospective cohort study was conducted in a diverse community population of patients 18 years or older with ERM who were hospitalized across Kaiser Permanente Northern California between January 1, 2009, and December 31, 2019. Patients were initially identified through electronic screening for all-cause rhabdomyolysis admissions, followed by manual medical record reviews to verify their eligibility for the study. The diagnosis of AKI and chronic kidney disease (CKD) was determined using KDIGO (Kidney Disease Improving Global Outcomes) criteria and confirmed by medical record review. Data analysis was performed from October 1, 2023, to January 31, 2024.ExposuresHistory of strenuous physical exercise before hospitalization for ERM.Main outcome and measuresDevelopment of AKI, CKD, and compartment syndrome and number of deaths.ResultsAmong 3790 patients hospitalized for rhabdomyolysis between 2009 and 2019 in Kaiser Permanente Northern California, 200 (mean [SD] age, 30.5 [8.5] years; 145 [72.5%] male) were confirmed to have ERM via medical record review. Seventeen patients (8.5%) developed AKI, none developed CKD, 1 (0.5%) developed compartment syndrome, and there were no fatalities. There was no association between serum CK levels and the risk of AKI. However, the risk of AKI was significantly higher in patients with ERM who used nonsteroidal anti-inflammatory drugs (NSAIDs) before admission (11 of 17 with AKI [64.7%] vs 40 of 183 without AKI [21.9%], P < .001) or experienced dehydration (9 of 183 without AKI [52.9%] vs 9 of 17 with AKI [4.9%], P < .001). This analysis suggests that eliminating preadmission NSAID use and dehydration could reduce the risk of potential AKI in patients with ERM by 92.6% (95% CI, 85.7%-96.1%) in this population.Conclusions and relevanceThe findings of this cohort study of hospitalized patients with ERM suggest that serum CK elevation alone is insufficient as an indicator of AKI in patients with ERM. Concurrent risk factors, such as NSAID use or dehydration, may be associated with AKI development in patients with ERM.

Dataset Information

Recombinant antithrombin attenuates acute kidney injury associated with rhabdomyolysis: an in vivo animal study.

Background

Results

Conclusions

Publications

Recombinant antithrombin attenuates acute kidney injury associated with rhabdomyolysis: an in vivo animal study.

Similar Datasets

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