The effects of the combination of anti-IL-1β and anti-TNF-α antibodies on acute kidney injury following hemorrhagic shock. The main purpose of this study was to observe the combined effect of anti-IL-1β antibody (IL-1βAb) and anti-TNF-α antibody (TNF-αAb) on acute kidney injury (AKI) following hemorrhagic shock (HS). AKI was induced by withdrawing blood from Sprague-Dawley (SD) rats to a mean arterial pressure (MAP) of 35 mmHg for 60 min followed by fluid resuscitation with saline (0.3 mL/100 g body weight) or shed blood at 1 h after blood withdrawal, and the animals were randomly divided into the following 5 groups: Group I, sham group; Group II, HS group; Group III, mice which had received IL-1βAb (0.2 mg/kg) at 1 h before sham operation; Group IV, mice which had received TNF-αAb (1 mg/kg) at 1 h before sham operation; Group V, mice which had received combination of IL-1βAb (0.2 mg/kg) and TNF-αAb (1 mg/kg) at 1 h before sham operation. The changes of kidney tissues and urinary concentrations of blood urea nitrogen (BUN) were observed at 3 and 6 h after the sham operation or HS, and the ultrastructure of kidney tissues were observed at 6 h after the sham operation or HS. The urinary levels of renal injury biomarkers [kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG)] and tubular epithelial cell injury biomarkers [lipocalin 2 (LCN2), aquaporin-1 (AQP1), osteopontin (OPN)] were measured at 6 h after the sham operation or HS. Compared with those of the sham operation group, the levels of BUN and the urinary concentrations of KIM-1, NGAL, NAG, LCN2, AQP1 and OPN were significantly increased at 3 and 6 h after the sham operation or HS. Compared with Group III, the levels of BUN and the urinary concentrations of KIM-1, NGAL, NAG, LCN2, AQP1 and OPN were significantly increased at 3 and 6 h after the sham operation or HS in the IL-1βAb group. Compared with those of the TNF-αAb group, the levels of BUN and the urinary concentrations of KIM-1, NGAL, NAG, LCN2, AQP1 and OPN were significantly increased at 3 and 6 h after the sham operation or HS in the IL-1βAb+TNF-αAb group. Compared with those of the sham operation group, the levels of BUN and the urinary concentrations of KIM-1, NGAL, NAG, LCN2, AQP1 and OPN were significantly increased at 3 and 6 h after the sham operation or HS in the IL-1βAb+TNF-αAb group. The kidney injury was greater in the combination group than in the IL-1βAb group. Combined IL-1βAb and TNF-αAb treatment resulted in aggravated AKI following HS in rats. The combined treatment of IL-1βAb and TNF-αAb might contribute to the development of AKI after severe HS.