Ultrastructural Analysis of AKI due to Rhabdomyolysis
- AKI: Mechanisms - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
- Orihara, Seira, Gifu University Graduate School of Medicine, Gifu, Japan
- Miyake, Yuta, Gifu University Graduate School of Medicine, Gifu, Japan
- Miura, Tomotaka, Gifu University Graduate School of Medicine, Gifu, Japan
- Kuroda, Ayumi, Gifu University Graduate School of Medicine, Gifu, Japan
- Suzuki, Kodai, Gifu University Graduate School of Medicine, Gifu, Japan
- Takada, Chihiro, Gifu University Graduate School of Medicine, Gifu, Japan
- Okada, Hideshi, Gifu University Graduate School of Medicine, Gifu, Japan
Rhabdomyolysis (RM) develops due to being caused by skeletal muscle damage. The breakdown products are released into the bloodstream and filtered by glomeruli, causing tubular obstruction and inflammation due to protein precipitation. These injured the renal tubular and endothelial cells of the kidney and lead to acute kidney injury (AKI). However, the mechanism is still unclear. In this study, we analyzed the ultrastructure of the renal tubular and the endothelial glycocalyx in RM with scanning electron microscopy (SEM).
Ten-week-old male C57BLB6 mice were injected intramuscularly into the left thigh of the mice at a dose of 5 mL/kg of 50% glycerol after 24 hours of fasting to create an RM model mouse. The mice that survived were euthanized 96 hours after injection, and then kidney specimens and blood samples were obtained. To investigate the ultrastructure of the kidney, the glycocalyx fixation method, and the conventional fixation method were performed. Mice were perfused with a solution composed of glutaraldehyde with/without lanthanum nitrate at a steady flow rate.
Serum blood urea nitrogen and creatinine were significantly elevated in the RM group. SEM analysis revealed that renal tubules are nourished by capillaries flowing through their interstices, and in normal kidneys, tubules and capillaries exist in close contact. However, in AKI induced by RM, a gap with fibrosis is created around the capillaries, creating a distance between the capillaries and the tubules. The surface of the proximal tubular cells in normal kidneys is densely packed with microvilli of unequal length and thickness, forming a brush border. In RM, microvilli on the surface of the proximal tubules had disappeared and their density was sparse. Under the RM condition, the endothelial glycocalyx was disrupted compared to the control group.
In conclusion, our data have shown the renal tubular and the vascular endothelial glycocalyx were injured and the newly formed gap creates a distance between them.