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

Intensive Care Medicine Experimental · 28 authors, 7 centres

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TL;DR

Male B6 mice were treated with rAT or saline at 24 and 72 hours post-injury and euthanized at 96 hours for analysis.

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Male B6 mice were treated with rAT or saline at 24 and 72 hours post-injury and euthanized at 96 hours for analysis. Histological analysis revealed that rAT attenuated tubular epithelial cell damage, increased Ki-67-positive nuclei suggesting tubular regeneration, reduced shedding of renal tubule microvilli, and restored vascular endothelial glycocalyx function. The study concludes that rAT attenuates proximal tubular injury through anti-inflammatory effects and accelerated restoration of endothelial cells and tubules. Limitations include the exclusive use of male mice, the inability to distinguish between direct rAT effects and indirect vascular effects, and the need for quantitative methods to assess glycocalyx shedding and microvilli.

STUDY TYPE

other

SPECIALTY

nephrology

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AI pipeline

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100% · A

ORIGINAL PAPER

PMC10822833

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

Intensive Care Medicine Experimental

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ABSTRACT

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. Supplementary Information The online version contains supplementary material available at 10.1186/s40635-024-00594-y. Keywords: Acute kidney injury, Rhabdomyolysis, Recombinant antithrombin, In vivo mice model, Novel treatment

CITATION EXPORT

Tomotaka Miura, Tomoki Okuda, Kodai Suzuki et al.. Recombinant antithrombin attenuates acute kidney injury associated with rhabdomyolysis: an in vivo animal study. Intensive Care Medicine Experimental. (2024). https://doi.org/10.1186/s40635-024-00594-y

AUTHORS

28 · 7 CENTRES

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

1Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194 Japan
2Department of Infection Control, Gifu University Graduate School of Medicine, Gifu, Japan
3Center for One Medicine Innovative Translational Research, Gifu University Institute for Advanced Study, Gifu, Japan
4Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194 Japan
5Department of Pharmacy, Gifu University Hospital, Gifu, Japan
6Abuse Prevention Center, Gifu University Graduate School of Medicine, Gifu, Japan
7Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan