Effects of Valproic Acid and Dexamethazone in Acute Kidney Ischemia-Reperfusion Injury Model (P2216)

Abstract Introduction: Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high mortality and morbidity. The objective of this study was to ameliorate kidney IR injury and identify novel biomarkers for AKI. Methods: Left renal ischemia was induced in Wister rats by clamping the renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n=8/group) received Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (Saline) IP. Animals were sacrificed at 3h, 24h or 120h IR and blood, urine and kidney were collected. Results: At 3h IR, urine albumin was lower (P>0.05) in VPA (0.84±0.62) and Dex (1.04±0.73) compared to Vehicle (1.47±1.02 mg/ml) group; and Lipocalin-2 was lower (P<0.006) in Dex (0.42±0.15) and higher (P<0.01) in VPA (1.21±0.32) compared to Vehicle (0.77±0.31 µg/ml) group. Osteopontin was higher (P<0.05) at 24h IR in VPA and Dex . TIM-1 did not differ. Serum creatinine (mg/dL) at 24 h IR in VPA (2.7±1.8) and Dex (2.3±1.2) was reduced (P<0.05) compared to Vehicle (3.8±0.5). Histopathology at 3h IR demonstrated reduced (P<0.04) ischemic changes in the renal cortex in VPA (27± 32 %) compared to Vehicle (56±27%) group. Tubular necrosis in the outer medulla was lower (P<0.02) in Dex and VPA (43-45%) compared to Vehicle (70%) at 24h IR. BCL-2 as determined by RT-PCR did not differ. Conclusion: The VPA administration prior to surgery appears to offer renal protection from IR injury.