Early treatment with GLP-1 following severe trauma preserves renal function in obese Zucker rats.

Early post-trauma hyperglycemia (EPTH) is correlated with later adverse outcomes including acute kidney injury (AKI). We have shown that following orthopedic trauma, obese Zucker rats (OZ) exhibit EPTH and a later development of AKI (within 24 hours). We hypothesized that GLP-1 treatment after trauma decreases EPTH and protects renal function in OZ. OZ were fasted for 4 hours before trauma. Soft tissue injury, fibula fracture, and homogenized bone component injection were then performed in both hind limbs to induce severe extremity trauma. Plasma glucose levels were measured before and 15, 30, 60, 120, 180, 240, and 300 minutes after trauma. GLP-1 (3mg/kg/h, 1.5ml/kg total) or saline was continuously infused from 30 minutes to 5 hours after trauma. Afterwards, rats were placed in metabolic cages overnight to collect urine. The following day, plasma IL-6 levels, renal blood flow (RBF), GFR, and renal oxygen delivery (DO2 ) and consumption (VO2 ) were measured. EPTH was evident within 15 minutes after trauma but was significantly ameliorated during the 5 hours of GLP-1 infusion. One day after trauma, plasma IL-6 was markedly increased in the trauma group and was decreased in GLP-1-treated animals. RBF, GFR, and DO2 all significantly decreased with trauma, but renal VO2 was unchanged. GLP-1 treatment normalized RBF, GFR, and DO2 without affecting VO2 . These results suggest that GLP-1 decreases EPTH and protects against a later development of AKI. Early treatment with GLP-1 to rapidly, effectively, and safely control EPTH may be beneficial in the pre-hospital care of obese patients after trauma.