The diagnostic value of urinary neutrophil gelatinase-associated lipocalin (NGAL) to the acute kidney injured septic rats

Abstract

Objective ①Observing urinary neutrophil gelatinase-associated lipocalin (uNGAL) ' s concentration variation under the intervention of sepsis; ②Evaluatingu NGAL' s diagnostic value for earlyacute kidney injury (AKI). Method Fifty-six SD (Sprague Dawley) rats were randomly (random number) divided into four groups, including 16 rats in model group (CLG) , 16 rats in Xuebijing group (XBG) , 16 rats in Huangqi and Chaihu injection jointly applied group (HCG) , and 8 rats in sham operation group (SOG). The septic models in CLG group, HCG group and XBG group were established by cecal ligation and puncture (CLP). Then, the rats in HCG group was treated with intraperitoneal injectionby Huangqi and Chaihu injections; the XBG group was treated with intravenous injection by Xuebijing injection; the SOG group was treated with open surgery without CLP. After the CLP, serial urine and serum samples were obtained at baseline (just prior to operation) , 6 h, 12 h, 18 h, 24 h, 36 h, 48 h, and 72 h, and were measured by sCr, uCr, uNa, and uNGAL. The line graph of uNGAL' s concentration variation was plotted, based on the time. Diagnostic characteristics of urinary NGAL in predicting AKI were assessed by calculating the area under the receiver operating characteristic curve (AUC). Results After the CLP, the uNGAL of sepsis model rats increased quickly within 6 hours. The time points of each group model reaching their peak were 6 hours after CLP in CLG groupand 24 hours after CLP in HCG group and XBG group. These groups' uNGAL all decreased quickly after the peak. The cuNGAL of sepsis model rats was increased quickly within 6 hours after CLP, reached its peak at 24 hours after CLP. In CLG group, the line graphs of uNGAL or cuNGAL were almost overlapped. There is little difference in the concentration of uNGAL or cuNGAL at each time point (uNGAL: 6 h, t =0.691 ; 12 h, t =1.627; 18 h, t =0.511. cuNGAL: 6 h, t =0.371 ; 12 h , t =0.474 ; 18 h , t =-1.187.Statistical significance of all above value wasP >0.05). In XBG group, the line graph of uNGAL and cuNGAL were not overlapped, but difference between uNGAL and cuNGAL concentration at each time point was not significant (uNGAL: 6 h, t =1.222; 12 h, t =1.178; 18 h, t =1.272; 24 h, t =0.918; 36 h, t =0.442.cuNGAL: 6 h, t =1.482; 12 h, t =1.314; 18 h, t =1.280 ; 24 h , t =0.280 ; 36 h , t =0.467.Statistical significance of all above value wasP >0.05). In HCG group, uNGAL of AKI rats were higher than non-AKI rats at each time points since 6 hours later (6 h, t =2.351, P<0.05; 12 h, t=3.086, P<0.01; 18 h, t=2.535, P<0.05; 24 h, t=2.150, P<0.05; 36 h, t =2.485 , P <0.05) ,The average cuNGAL of AKI rats and non-AKI rats have statistical significance at 6 h, 18 h, and 24 h (6 h, t =3.013. P<0.01; 18 h, t =4.804, P<0.01; 24 h, t =2.682, P<0.05). At 6 h, Uout can increase cuNGAL' s ability of predicting AKI' s occurrence in 24 hours (AUC increased from 0.839 to 0.900, P <0.05). Conclusions The intervention to the sepsis rats have influence on the secretion volume and secretion sequence of NGAL in rat urine. uNGAL and cuNGAL are good predictor of AKI occurrence in sepsis rats. Key words: Neutrophil gelatinase-associated lipocalin; Biomarker; Acute kidney injury; Sepsis; Cecal ligation and puncture; Receiver operating characteristic curve; Area under receiver operating characteristic curve; Diagnosis; Prognosis