ArticleBone & joint research2026
Transient acute kidney injury following femoral fracture in mice : the role of sympathetic activation.
Article in Bone & joint research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Aims: Femoral shaft fractures are commonly associated with high-energy trauma, and affect individuals of all ages. Kidney dysfunction frequently complicates fracture healing, and trauma-related acute kidney injury (TRAKI) elevates the risk of adverse outcomes. The mechanisms of post-fracture kidney injury, particularly the involvement of sympathetic activation, remain poorly understood. We aimed to define the impact of femoral fracture on the kidney and investigate mechanistically the potential contribution of sympathetic activation. Methods: A total of 46 female C57BL/6J mice were subjected to femoral shaft fracture and external fixation, and received daily treatment for three days with either phentolamine, propranolol, or butoxamine. They were analyzed early (at day 1) and late at day 21 post-fracture. Renal function was assessed via blood urea nitrogen measurement, while kidney injury was evaluated using histology and gene expression analysis. Results: While renal function remained within the physiological range, animals with fracture revealed signs of kidney damage one day after fracture, reflected by increased expression of kidney damage markers and oxidative stress indicators and histopathological changes. Cellular inflammation and proliferation were induced upon fracture but did not cause long-term fibrosis. By 21 days, these effects were no longer detectable, suggesting transient TRAKI. Adrenergic receptor (AR) blockade experiments clearly indicated a sympathetic contribution to this temporal renal response. α-AR-mediated effects in particular modulated the kidneys' response to oxidative stress, as phentolamine treatment reduced early oxidative stress markers. Furthermore, immune activation was only detected upon propranolol application. However, none of the treatments provided a sustained protective effect. Rather, a mixed outcome was observed in different aspects of TRAKI. Conclusion: Taken together, femoral fractures in mice can induce transient mild kidney injury, local cellular damage, and inflammation, while maintaining renal function. Adrenergic signalling appears to contribute to TRAKI development, which warrants further mechanistic investigation.
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