Effects Of Sevoflurane On Renal Ischemia And Reperfusion Injury In Patients Undergoing Living Donor Renal Transplantation

Part one Effects of sevoflurane preconditioning on renal ischemia and reperfusion injury in patients undergoing living donor renal transplantationBackground:The grafted kidney is bound to experience two stages of ischemia(warm and cold ischemia),so that the ischemia-reperfusion injury(IRI)is an inevitable event accompanying renal transplantation.The severity of IRI correlates with recovery of graft function,episodes of transplant rejection and survival of the transplanted kidney,which may greatly influence the short-term and long-term outcomes.Recent studies have found that sevoflurane protect kidney from IRI in vitro and in animal studies,however,whether sevoflurane preconditioning(SpreC)can attenuate IRI in renal recipients,undergoing living donor renal transplantation,have not been reported.Objective:The aim was to evaluate the effects of SpreC on renal IRI in patients undergoing living donor renal transplantation.Methods:This prospective study included 60 pairs of patients who underwent first living donor renal transplantation in the Kidney Disease Center,First Affiliated Hospital,Medical College of Zhejiang University,from August 2014 to October 2015.The paired patients were randomly assigned to the Control group and SpreC group according to the use of sevoflurane or not,each group included 30 pairs of patients.Anesthesia was performed continuously by intravenous infusion of propofol and remifentanil for all donors and recipients.In Control group,neither donors nor recipients inhaled sevoflurane during the operation.In SpreC group,donors were preconditioned with 3%sevoflurane and propofol was replaced for 30 min before grafted renal inflow occlusion.We recorded hemodynamics,such as heart rate(HR),mean arterial pressure(MAP)of all donors and recipients during the operation.Blood samples of recipients were collected to detect serum creatinine(SCr),blood urea nitrogen(BUN),Cysteine protease inhibition of protein C(Cys-C),Neutrophil Gelatinase Associated Lipocalin(NGAL),IL-10 and IL-1β,and estimated glomerular filtration rate(eGFR)was calculated before and after transplantation.Daily urinary output was also collected to detect the urinary protein quantity and urinary creatinine of 24 h.Postoperative complications and the duration of hospital stays were compared between two groups.Results:Comparison of hemodynamic parameters:At 15 min and 30 min after SpreC,HR of donors in SpreC group was faster than that in the Control group(P<0.001).However,there was no significant difference in MAP between two groups(P>0.05).Comparison of the renal function index:Compared with the Control group,urinary output was less in the SperC group at 24 h after transplatation(P<0.05).The serum NGAL was lower in Control group at 6 h after transplantation compared with the SperC group(P<0.05).There were,however,no significant differences in SCr,BUN,eGFR,Cys-C,the urinary protein quantity and urinary creatinine of 24 h between two groups(P>0.05),Comparison of postoperative inflammatory reaction:The concentrations of IL-10 and IL-1(3 increased from reperfusion,peaked at 3-6 h after reperfusion,and then began to recover.However,there were no significant differences in the serum level of IL-10 and IL-1β between the SperC and Control group at each point after reperfusion(P>0.05).The white blood cell count in the control group was higher than that in the SperC group at the 4th day after transplantation(P<0.05),however,there was no significant difference at other points in the first week after transplantation between the two groups(P>0.05).Conclusion:This randomized trial preliminarily showed that SperC could not protect the grafted kidney against ischemia reperfusion injury in living donor renal transplantation,even might transiently supress postoperative renal function after transplantation.Part two Effects of sevoflurane postconditioning on renal ischemia and reperfusion injury in patients undergoing living donor renal transplantationObjective:The aim of this study was to evaluate the effects of sevoflurane postconditioning(SpostC)on renal IRI in patients undergoing living donor renal transplantation.Methods:This prospective study included 60 pairs of patients who underwent first living donor renal transplantation in the Kidney Disease Center,First Affiliated Hospital,Medical College of Zhejiang University from August 2014 to October 2015.The paired patients were randomly assigned to the Control group and SpostC group according to the use of sevoflurane or not in the recipients,each group had 30 pairs of patients.Anesthesia was performed continuously by intravenous infusion of propofol and remifentanil for all donors and recipients.In Control group,neither donors nor recipients inhaled sevoflurane during the operation.In SpostC group,recipients were postconditioned with 3%sevoflurane and propofol was replaced for 30 min at the onset of reperfusion.We recorded hemodynamics,such as HR,MAP in all donors and recipients during the operation.Blood samples of recipients were collected to detect SCr,BUN,Cys-C,NGAL,IL-10 and IL-1β,eGFR was calculated before and after transplantation.Daily urinary output was also collected to detect the urinary protein quantity and urinary creatinine of 24 h.Postoperative complications and the duration of hospital stays were compared between two groups.Results:Comparison of hemodynamic parameters:There were no significant differences in MAP and HR of donors between the SpostC and Control group(P>0.05).At 15 min after SpostC,HR of recipients in SpostC group was significantly faster and the MAP was significantly lower than those in the Control group(P<0.001).Comparison of the renal function index:Compared with the Control group,urinary output was also less in SpostC group at 3 h and 24 h after transplatation(P<0.05).The serum NGAL in Control group at 6 h after transplantation was lower compared with the SpostC group(P<0.05).However,there were no significant differences in SCr,BUN,eGFR,Cys-C,the urinary protein quantity and urinary creatinine of 24 h at each point between two groups(P>0.05).Comparison of postoperative inflammatory reaction:The concentrations of IL-10 and IL-1β were rise from reperfusion,peaked at 3-6 h after reperfusion,and then began to recover.Compared with the Control group,SpostC group had an increased IL-10 at 3,6,24 hours after reperfusion,a decreased the IL-1β at 6 h after reperfusion,and a reduced leukocyte counts in peripheral blood at 1st,2nd and 4th day after transplantation.Conclusion:This randomized trial preliminarily showed that SpostC could not protect the grafted kidney against ischemia reperfusion injury in living donor renal transplantation,even might transiently supress postperative renal function after transplantation.However,our trial showed that sevoflurane has potiential anti-inflammatory properties and may contribute to regulate the inflammatory reaction after living donor renal transplantation.Part three Influence of sevoflurane perconditioning and postconditioning on one-year outcomes of patients in living donor renal transplantationObjective:The aim of this study was to evaluate the influence of sevoflurane perconditioning and postconditioning on one-year outcomes of patients in living donor renal transplantation.Methods:This study included 90 patients,who were recruited to the group of Control,SpreC and SpostC in section one and two after renal transplantation,during August in 2014 and October in 2015.The follow-up study included 15 days,1 month,3 months,6 months and 12 months after surgery.The main content of this follow-up study included the levels of SCr,BUN,eGFR and the concentrations of Hb and Alb.And we also analyzed the incidences of complications,such as acute or chronic rejection,renal allograft dysfunction,renal infection and recurrence of nephritis.Results:There were no significant differences in the levels of SCr,BUN and eGFR at all specified time points within a year among the three groups.However,the level of Hb at 6 months and 12 months in the Control group were higher than those in the SpreC group(P<0.01).The level of Hb at 3 months of Control group was also higher than that in the SpostC group(P<0.05).Although the level of Alb at 6 months and 12 months in the Control group was tended to be higher than that in the SpostC and SpreC group,there is no statistical difference(P>0.05).The renal complications in the Control group(one case),was lower than those in the SpreC group(8 cases)and SpostC(6 cases)within a year,but there is no statistical difference(P>0.05).Conclusion:SpreC and SpostC have no significant impact on the renal function after renal transplantation within a year.