Effects Of Different Anesthesia Methods On Acute Kidney Injury After Living Donor Liver Transplantation In Infants And The Mechanism

Part I: Acute kidney injury after living relative liver transplantation in infants with biliary atresia: A retrospective studyBackground: Living relative liver transplantation(LRLT)is one of the most effective methods to treat children with end-stage liver disease,which can not only solve the serious shortage of liver source,but also reduce the mortality of children with end-stage liver disease.LRLT is the main type of pediatric liver transplantation in China.With the gradual maturity of surgery and anesthesia technology,infant liver transplantation has been widely carried out,and the success rate of surgery has been significantly improved,the surgery-related mortality has been significantly reduced,and the quality of life and long-term prognosis of children after transplantation have also been improved.However,complications after liver transplantation are still the main cause of death in perioperative children,and have become one of the important factors restricting the further development of liver transplantation.Acute kidney injury(AKI)is one of the most common complications after liver transplantation.The incidence of AKI in adult population has been reported in previous studies,ranging from 10-90%,and is closely associated with increased mortality.At present,there are few studies on the occurrence and prognosis of AKI after LRLT in infants,and the risk factors related to AKI after liver transplantation in infants have not been determined.Methods:We retrospectively reviewed infants who underwent LRLT surgery between January 2018 and January 2021.The primary outcome was the risk of postoperative AKI occurrence in the first 7postoperative days.A multivariate regression analysis model was used to investigate risk factors for AKI,and the incidence and impacts of AKI on outcomes were analyzed.Results: A total of 98 patients were included in the analysis.AKI occurred in 59 patients(60.2%)within 7 days after surgery,including29.6% in stage I,18.4% in stage 2 and 12.2% in stage 3.Logistic regression analysis revealed that preoperative transfusion(P=0.047)and lower SCr preoperatively(P=0.010)were independent risk factors for AKI.The incidence of serious complications was significantly higher in the AKI group than in the non-AKI group(37.3% vs.18.0%,P=0.045).The postoperative mechanical ventilation time(P=0.046)and hospital stays(P=0.013)was significantly longer in the AKI group.There was no evidence of CKD in any surviving infants within 1 year after surgery.Conclusions: AKI is common in infant LDLT,and preoperative transfusion and lower SCr levels were independently associated with AKI.AKI may be related to prolonged use of ventilators and hospital stays.Renal function in infants with AKI can be highly recovered after LDLT,and no CKD occurred within 1 year.Part Ⅱ: Impact of Propofol-based vs.Desflurane-based Anesthesia on Postoperative Hepatic and Renal Functions Following living relative liver transplantation in infants: A randomized Controlled TrialBackground: The choice of anesthetic can significantly impact postoperative liver and renal function in liver transplantation.Both desflurane and propofol have demonstrated organ protective effects,as they protect against hepatic ischemia-reperfusion(HIRI)injury.However,our understanding of the effect of anesthetics on liver and renal function after living related liver transplantation(LRLT)in infants remain limited.This study is designed to investigate the postoperative liver and renal function in infant recipients who umderwent anesthesia with either propofol-based total intravenous anesthesia(TIVA)or desflurane-based inhalational anesthesia.Additionally,the study aims to assess the influence of HIRI on the development of acute kidney injury(AKI)after LRLT.Methods: A total of 76 infants diagnosed with biliary atresia and scheduled for LRLT were subjected to random assignment.These infants were divided into two groups: Group D,receiving continuous inhalation of desflurane,and Group P,receiving infusion of propofol.The primary focus of this study was to assess changes in liver transaminase and creatinine levels during the initial 7 days following surgery,within each group.Additionally,peak aminotransferase levels within 72 hours post-surgery served as a surrogate marker for HIRI.AKI was defined according to the criteria set forth by Kidney Disease: Improving Global Outcomes(KDIGO).A comprehensive comparison was undertaken,focusing on the demographic characteristics,intraoperative clinical data and hemodynamic parameters of the two groups.Furthermore,the study meticulously recorded and rigorously analyzed the incidence of post-operative complications and clinical outcomes in both groups.Results: Upon arrival in the Intensive Care Unit(ICU),the levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in group P were significantly lower than those observed in group D.This difference persisted on postoperative days 3 and 4.The peak AST level[856(552,1221)vs.1468(732,1969),P=0.001] and ALT level[517(428,704)vs.730(541,1100),P=0.006] within 72 hours after surgery were markedly lower in Group P.In terms of Scr,Group P exhibited notably lower levels upon arrived in the ICU and on the first postoperative day,compared to group D.Compared with group D,the levels of retinol-binding protein(U-RBP),N-acetyl β-D-glucosidase(U-NAG)and cystatin C(Cys-C)in group P were significantly decreased two hours after reperfusion(P<0.05);Urinary creatinine(U-Cr)level was significantly decreased(P<0.05);The incidence of severe AKI(stage AKI-1 defined as mild AKI,stage 2-3 AKI defined as severe AKI)in group P experienced a significant reduction(15.8% vs.39.5%,P=0.038)in comparison to Group D.Throughout the surgical procedure,there were no significant differences observed in hemodynamic parameters between the two groups during surgery.Notably,the incidence of postoperative complications,duration of mechanical ventilation,length of ICU stay,and length of hospital stay demonstrated comparability between the two groups.Conclusion:The implementation of propofol-based total intravenous anesthesia demonstrates a substantial capacity to mitigate ischemia-reperfusion-induced liver injury,facilitate the restoration of liver function,and notably diminish the occurrence of severe Acute Kidney Injury(AKI)in the context of infant living related liver transplantation(LRLT).However,further in-depth investigations are necessary to provide a more comprehensive understanding of the precise mechanisms underpinning this beneficial association.Part III: Mechanism of organ protection effect of propofol intravenous anesthesia in living relative liver transplantation of infantsBackground: A large number of studies have shown that liver ischemia-reperfusion injury(IRI)after reperfusion of new liver during liver transplantation can contribute to the progression of acute kidney injury(AKI)by promoting inflammation,apoptosis and fibrosis.Liver reperfusion injury during Liver transplantation(LR)is an important cause of AKI.Different anesthesia methods have different effects on postoperative renal function,which may be closely related to liver reperfusion injury,but its mechanism is still unclear.In this part of the study,cytokine levels in blood before and after intraoperative reperfusion in relatives living donor liver transplantation children who received total intravenous anesthesia based on propofol(TIVA)or inhalation anesthesia based on desflurane were determined,and the transcriptome differential genes among different specimens were preliminatively screened by RNA Seq technique.Bioinformatics methods were used to analyze and screen out the genes and signaling pathways with significant differences,providing exploration directions for finding the pathogenesis of pathological processes and potential therapeutic targets for new clinical therapies.Methods: The specimens were examined from the second part of the study.The levels of serum inflammatory cytokines TNF-alpha,IFN-alpha,IL-2,IL-4,IL-5,IL-6,IL-8 and IL-10 were measured by Fluidic cell method.RNA in blood samples was extracted and transcriptomically analyzed for significant differential expression before and after reperfusion between the two groups.Gene GO function enrichment prediction and KEGG biological pathway enrichment analysis were performed for RNAs with the same and opposite changes in direction.Result :Compared with before reperfusion,the serum concentrations of IL-6,IL-8 and IL-10 in 2 groups were significantly increased(P<0.05),and the concentrations of other inflammatory factors were not significantly abnormal at 2 time points(P>0.05).Compared with group D,the levels of pro-inflammatory factors IL-6 and IL-8 in serum of group P after reperfusion were significantly decreased(P<0.05),the levels of anti-inflammatory factor IL-10 were significantly increased,and the other inflammatory factors were not significantly different(P>0.05).Transcriptomic sequencing(RNA-seq)revealed 9 differentially expressed genes.We screened the genes related to immunity,inflammation and ischemia reperfusion for further RT-PCR verification.Combined with KEGG and GO cluster analysis,we found that,Downregulation of CLEC10 A gene and STEAP3 gene after venous reperfusion may be one of the molecular mechanisms of organ protection of propofol and a potential target for treatment of ischemia-reperfusion injury.Conclusion: The protective effect of propofofo-based intravenous anesthesia on organ function in infant donor liver transplantation is closely mediated by reducing inflammatory response,and the mechanism may be closely related to the downregulation of CLEC10 A and STEAP3 genes.This part of the study provides novel and precise potential therapeutic targets for developing new clinical therapeutic methods.