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Attenuation of Post‐Trauma Hyperglycemia Prevents Acute Kidney Injury in Obese Rats
Author(s) -
Mittwede Peter,
Lu Silu,
Clemmer John,
Hester Robert,
Xiang Lusha
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.800.6
Subject(s) - medicine , renal function , endocrinology , acute kidney injury , context (archaeology) , orthopedic surgery , surgery , biology , paleontology
Traumatic injury is one of the leading causes of death in the United States, and obese patients have an increased risk of developing post‐trauma acute kidney injury (AKI). Hyperglycemia after trauma is correlated with worse outcomes, but whether it contributes to AKI in the context of obesity is not known. We hypothesized that blunting the hyperglycemic response would prevent AKI in obese rats. Lower‐limb orthopedic trauma was induced in lean (LZR) and obese (OZR) Zucker rats (12wk) by fibula fracture, soft tissue injury, and bone component injection. Plasma glucose levels were measured for five hours after trauma, and glomerular filtration rate (GFR) and plasma interleukin‐6 (IL‐6) were measured the day after trauma and in non‐trauma control rats (all groups n蠅6). OZR had higher peak glucose levels after trauma than LZR (275±19 vs 167±13 mg/dL; p<.05) as well as prolonged hyperglycemia. Treatment of the OZR after trauma with glucagon‐like peptide‐1 (GLP‐1), an incretin with insulinotropic effects (3μg/kg/hr IV), reduced peak glucose levels to 152±12 mg/dL (p<.05). In LZR with trauma, GFR did not decrease as compared to controls (1.44±0.1 vs 1.67±0.2 mL/min/g), while OZR with trauma had significantly decreased GFR as compared to controls (0.96±0.1 vs 1.92±0.1 mL/min/g; p<.05). Treatment with GLP‐1 in OZR prevented this decrease (1.98 mL/min/g; p<.05). IL‐6 levels were increased in LZR with trauma as compared to controls (400±114 vs 77±12 pg/dL; p<.05), while OZR with trauma had a larger increase (3834±1099 vs 75±6 pg/dL for OZR control; p<.05), and GLP‐1 treatment decreased IL‐6 levels (269±15 pg/dL; p<.05). These data suggest that acute hyperglycemia contributes to increased inflammation and AKI development after trauma in obesity.