RESUMEN
INTRODUCTION: Renal ischemia reperfusion injury is a major cause of perioperative acute kidney injury. Alpha-1-antitrypsin (AAT), a protease inhibitor, might improve outcomes by reducing inflammation and apoptosis. We investigated the effects of a single intravenous dose of AAT immediately before ischemia in a rat bilateral renal clamping model. METHODS: Both renal pedicles of male Sprague-Dawley rats were clamped (45 min). Plasma and renal tissue were collected at 3 h, 24 h, and 7 d. Intravenous AAT (60 mg/kg) was administered 5 min before clamping. Controls received saline. Shams underwent surgery without clamping or injection. Kidney function was assessed by plasma creatinine; injury by aspartate aminotransferase, heart-type-fatty-acid-binding-protein, and histopathology. Renal gene expression of tumor necrosis factor α, interleukin (IL)-6, heat shock protein 70, Chemokine (C-X-C motif) ligand 2, cyclo-oxygenase 2, endothelin-1, IL-10, heme oxygenase 1, B-cell lymphoma 2, and bcl-2-like protein 4 were determined by quantitative reverse transcriptase polymerase chain reaction. RESULTS: None of the 3 h and 24 h end points were different between Control and AAT. In Sham, survival was 100% (6/6), 33% in Control (2/6), and 83% (5/6) in AAT (overall log-rank 0.03). At 7 d, plasma creatinine was lower with higher glomerular filtration rate in surviving AAT treated animals compared to Control (P < 0.001, P 0.03, respectively). These also had lower tumor necrosis factor α and IL-6 gene expression (P 0.001, P < 0.001, respectively). CONCLUSIONS: These data suggest that a single intravenous dose of AAT immediately before ischemia might affect proinflammatory gene expression, glomerular filtration rate and animal survival at 1 wk after reperfusion despite an absence of improvement in early renal function and injury. These findings deserve further investigating in sufficiently powered studies including both sexes.
