Protective effect of recombinant human brain natriuretic peptide on acute renal injury induced by endotoxin in canines.

Abstract

The objective of this study was to evaluate the protective effect of recombinant human brain natriuretic peptide (rhBNP) on endotoxin-induced acute kidney injury (AKI) in canine model of septic shock and its potential mechanisms. Dogs with endotoxin-induced septic shock were subjected to intravenous infusion of saline solution or rhBNP at the concentrations of 5 μg/kg (low-dose intervention group) or 10 μg/kg (high-dose intervention group). At 0, 2, 4, 8, and 12 h, the systemic vascular resistance index (SVRI) as well as serum levels of high mobility group box 1 protein (HMGB-1) and creatinine were measured, and kidney tissue samples were taken for histological examination. We have found that low and high doses of rhBNP could significantly reduce kidney tissue damage, such as tubular epithelial swelling and atrophy, and interstitial cell swelling in response to LPS injection in the dog sepsis models. rhBNP administration significantly reduced SVRI and serum levels of creatinine in dogs with LPS-induced sepsis in a dose-dependent manner, and attenuated the rise in the circulating HMGB-1. In conclusion, these findings suggest that rhBNP may exert dose-dependent protective effect on kidney tissue with endotoxin-induced injury, and this effect may be associated with the changes in blood levels of HMGB-1. rhBNP may be considered as therapeutic agents for treating sepsis-induced AKI.