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Published on: August 24, 2018
Valproic Acid Protects Against Acute Kidney Injury in Hemorrhage and Trauma
Ben E Biesterveld1, Ali Z Siddiqui1, Rachel L O'Connell2
1Department of Surgery, University of Michigan, Ann Arbor, MI.
Insights
Valproic acid (VPA) significantly improved survival and reduced kidney injury in swine models of trauma and shock. This study highlights VPA
Area of Science:
- Trauma and Emergency Medicine
- Nephrology
- Pharmacology
Background:
- Trauma is a leading cause of mortality in young individuals.
- Acute kidney injury (AKI) is a common complication in trauma patients, increasing mortality risk.
- Valproic acid (VPA) has demonstrated survival benefits in animal trauma models.
Purpose of the Study:
- To investigate the potential of VPA to attenuate AKI in swine models of lethal trauma.
- To evaluate the effect of VPA on survival rates and kidney function following severe injury.
Main Methods:
- Two swine models were used: hemorrhagic shock and polytrauma (including TBI, hemorrhage, fracture, crush, and liver laceration).
- Animals received normal saline (NS) with or without VPA (150 mg/kg) post-shock.
- Serum creatinine levels and kidney tissue proteomic analysis were performed.
Main Results:
- VPA treatment significantly improved survival in both models (80% vs. 20% and 83% vs. 17%).
- VPA administration attenuated the rise in serum creatinine levels in both hemorrhagic shock and polytrauma models.
- Proteomic analysis revealed VPA's impact on metabolic pathways within kidney tissue.
Conclusions:
- A single dose of VPA (150 mg/kg) provides significant protection against AKI in swine models of polytrauma and hemorrhagic shock.
- VPA demonstrates therapeutic potential for mitigating kidney injury in severe trauma scenarios.
Introduction:
Trauma is the leading cause of death among young people. These patients have a high incidence of kidney injury, which independently increases the risk of mortality. As valproic acid (VPA) treatment has been shown to improve survival in animal models of lethal trauma, we hypothesized that it would also attenuate the degree of acute kidney injury.
Methods:
We analyzed data from two separate experiments where swine were subjected to lethal insults. Model 1: hemorrhage (50% blood volume hemorrhage followed by 72-h damage control resuscitation). Model 2: polytrauma (traumatic brain injury, 40% blood volume hemorrhage, femur fracture, rectus crush and grade V liver laceration). Animals were resuscitated with normal saline (NS) +/- VPA 150 mg/kg after a 1-h shock phase in both models (n = 5-6/group). Serum samples were analyzed for creatinine (Cr) using colorimetry on a Liasys 330 chemistry analyzer. Proteomic analysis was performed on kidney tissue sampled at the time of necropsy.
Results:
VPA treatment significantly (P < 0.05) improved survival in both models. (Model 1: 80% vs 20%; Model 2: 83% vs. 17%). Model 1 (Hemorrhage alone): Cr increased from a baseline of 1.2 to 3.0 in NS control animals (P < 0.0001) 8 h after hemorrhage, whereas it rose only to 2.1 in VPA treated animals (P = 0.004). Model 2 (Polytrauma): Cr levels increased from baseline of 1.3 to 2.5 mg/dL (P = 0.01) in NS control animals 4 h after injury but rose to only 1.8 in VPA treated animals (P = 0.02). Proteomic analysis of kidney tissue identified metabolic pathways were most affected by VPA treatment.
Conclusions:
A single dose of VPA (150 mg/kg) offers significant protection against acute kidney injury in swine models of polytrauma and hemorrhagic shock.
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