Analysis Of Risk Factors For Early Acute Kidney Injury And Experimental Observation Of Renal Oxidative Stress After Liver Transplantation With Approach Of Retrograde Reperfusion

ObjectivesThis study included two parts: Objective of Part?was to identify risk factors for development of early acute kidney injury(EAKI)after orthotopic liver transplantation(OLT)with approach of retrograde reperfusion via inferior vena cava(RETR)by assessing the preoperative variables and the surgery-related events of patients;Objective of Part?was to investigate the impact of retrograde reperfusion via vena cava on renal oxidative stress injury after autologous OLT in rats.MethodsPart?: 321 adult(age?18 years)patients with end-stage liver disease who underwent OLT with approach of RETR from 2005 to 2015 at our centre were involved.Postoperative EAKI was defined in accordance with the clinical practice guidelines developed by Kidney Disease: Improving Global Outcomes(KDIGO)in 2012.Univariate and multivariate analysis were performed to determine the independent risk factors for EAKI following OLT.The discriminating power of model for end-stage liver disease(MELD)score and MELD incorporating with serum sodium(MELD-Na)score on EAKI outcome was evaluated by receiver operating characteristic(ROC)curve.Moreover,Spearman's correlation analysis was used for identifying the correlated relationship between MELD/MELD-Na score and the severity levels of EAKI.Part?: 24 male Sprague-Dawley(SD)rats were randomly divided into three groups,including sham operation(Sham)group,retrograde reperfusion via inferior vena cava(RETR)group and initial portal vein reperfusion(IPR)group,8 rats in every group.Rats models of autologous OLT were established in RETR and IPR groups.Retrograde reperfusion via inferior vena cava was applied in RETR group,whereas IPR group used the initial portal vein reperfusion.Kidney samples in all rats were taken at six hours after operation for light microscopic examination;renal cortex samples were homogenated to detect the content of malondialdehyde(MDA),8-hydroxy-2'-deoxyguanosine(8-OHdG),superoxide dismutase(SOD)and mitochondrial membrane potential(MMP,??m).ResultsPart?: The prevalence of EAKI following OLT with approach of RETR was in 206 of 321 patients(64.2%).Three risk factors for postoperative EAKI were presented: preoperative calculated MELD score(odds ratio(OR)=1.048,P=0.021),intraoperative volume of red cell suspension transfusion(OR=1.001,P=0.002),and preoperative liver cirrhosis(OR=2.015,P=0.012).Two areas under ROC curve(AUCs)of MELD/MELD-Na score predicting EAKI were 0.688 and 0.672,respectively;the difference between two AUCs was not significant(Z=1.952,P=0.051).The Spearman's correlation coefficients between MELD/MELD-Na score and the severity levels of EAKI were 0.406 and 0.385(P=0.001,0.001),respectively.Part?: Histological examination demonstrated no difference in degrees of tubular and interstitial damage between Sham group and RETR group(P=0.645),whereas degrees of tubular and interstitial damage of IPR group was significantly higher than in Sham and RETR group(P=0.005,P=0.038).Besides,there was a positive rank correlation relationship between degrees of tubular and interstitial damage with three groups(P=0.001),and Spearman's rank correlation coefficient was 0.628.Concentration of MDA and 8-OHdG in RETR group [(21.79±0.95)nmol/mg pro,(7.77±0.17)ng/ml] were significantly higher than in Sham group [(13.60±0.55)nmol/mg pro,(6.29±0.09)ng/ml;P<0.000,P=0.001],while were significantly lower than in IPR group [(24.96±0.68)nmol/mg pro,(8.58±0.21)ng/ml;P<0.001,P=0.001].Levels of SOD and ??m in RETR group [(1.46±0.05)U/mg pro,4.42±0.14] were significantly lower than in Sham group [(2.46±0.07)U/mg pro,6.05±0.32;P<0.001,P=0.001],however were significantly higher than in IPR group [(1.07±0.04)U/mg pro,3.77±0.08;P<0.001,P=0.001].ConclusionsPart?: Three independent risk factors for EAKI following OLT with approach of RETR,preoperative calculated MELD score,intraoperative volume of red cell suspension transfusion and preoperative liver cirrhosis were found.It was preliminarily validated that MELD score had a stronger power discriminating the post-OLT EAKI than the novel MELD-Na score.Part?: Approach of retrograde reperfusion via inferior vena cava significantly reduced the renal oxidative stress injury and consequently protected kidney against ischemia-reperfusion injury after autologous OLT in rats.