Kidney Week

Abstract: TH-PO295

Early Terlipressin Treatment for Hemorrhagic Shock-Induced AKI

Session Information

• AKI Basic: Oxidative Injury and Nephrotoxins
  November 02, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Acute Kidney Injury

• 001 AKI: Basic

Authors

• De Castro, Leticia U., University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil

Leticia U. De Castro,

• Otsuki, Denise A., University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil

Denise A. Otsuki,

• Sanches, Talita R., University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil

Talita R. Sanches,

• Maia, Débora R, University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil

Débora R Maia,

• Condor Capcha, Jose Manuel, University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil

Jose Manuel Condor Capcha,

• Malheiros, Denise M., University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil

Denise M. Malheiros,

• Malbouisson, Luiz M., University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil

Luiz M. Malbouisson,

• Andrade, Lucia, University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil

Lucia Andrade,

Background

Although hemorrhagic shock (HS) remains the leading cause of mortality, early vasopressor use might restore hemodynamic parameters and vital organ perfusion, thereby reducing the need for aggressive fluid therapy and avoiding fluid overload. However, that strategy has yet to be included in the Advanced Trauma Life Support guidelines. This study aimed to compare the effects of three different levels of lactated Ringer’s (LR) fluid therapy—aggressive (3× the blood volume removed, 3LR), conservative (2× the blood volume removed, 2LR) and low (1× the blood volume removed, 1LR)—with or without terlipressin (TLP), on acute kidney injury (AKI) in rats with HS.

Methods

We induced rats to HS, maintaining mean arterial pressure (MAP) at 30-40 mmHg for 60 min and thereafter submitting them to 30 min of LR fluid therapy, some rats also receiving TLP (10 µg/100 g BW, iv). Rats with HS were divided into 3 groups: 3LR, 1LR+TLP and 2LR+TLP. At 15 min after the end of the fluid therapy, the rats were resuscitated with the blood drawn previously. With the exception of MAP, which was measured at various time points, all studies were performed 24 h after HS induction. Data are mean±SEM.

Results

Mortality was 28%, 16% and 0% in 3LR, 1LR+TLP and 2LR+TLP rats, respectively. Creatinine clearance was higher in 2LR+TLP rats than in 1LR+TLP and 3LR rats (1.2±0.13 vs. 0.72 ± 0.1 and 0.53±0.2 ml/min/100 g BW, p<0.05). At 45 min after HS induction, MAP was higher in 2LR+TLP and 1LR+TLP rats than in 3LR rats. The acute tubular necrosis score was lower in 2LR+TLP rats than in 1LR+TLP and 3LR rats (5.8±0.8 vs. 14.2±3.5 and 18±4.3%, p<0.05). Protein expression of MnSOD was higher in 2LR+TLP rats than in 1LR+TLP and 3LR rats (130±7.1 vs. 110±4.5 and 103±4.3%, p<0.05). AQP2 expression was higher in 2LR+TLP and 1LR+TLP rats than in 3LR rats. TLR4 protein expression was lower in 2LR+TLP rats than in 1LR+TLP and 3LR rats (95±4.2 vs. 134±6.8 and 115±5.0%; p<0.05). There was less apoptosis (TUNEL-positive cells/0.087 mm2) in 2LR+TLP rats than in 1LR+TLP and 3LR rats (0.6±0.1 vs. 4.5±2.5 and 1.6±0.3; p<0.05).

Conclusion

Combining TLP with conservative fluid therapy appears to be a viable therapy for HS-induced AKI. We speculate that TLP attenuates AKI by modulating the inflammatory response via the TLR4 pathway. (FAPESP)

Funding

• Government Support - Non-U.S.