Study On The Value Of BK Virus Antibodies In Predicting The Development Of Posttransplant BK Virus Replication And BK Virus-Associated Nephropathy

【Background】Infection with BK virus(BKV)is a common one of postoperative complication in kidney transplant recipients,with 10%-20% developing viremia and 1%-10%progressing to BK virus-associated nephropathy(BKVAN),leading to allograft dysfunction or even graft loss,posing a serious impact to postoperative allograft survival in kidney transplant recipients.Maintenance immunosuppressive drugs modification are currently regarded as the therapeutic intervention of choice for BKVAN,and early postoperative screening for BKV infection in kidney transplant recipients is an important strategy to prevent BKVAN.【Objective】To explore the BKV antibodies different levels of pre-transplantation and post-transplantation in BKV infected and uninfected kidney transplant recipients,and analyze whether BKV antibodies can be used as one of the predictors of BKV infection to prevent BKV infection and improve allograft survival in recipients.【METHODS】Retrospective analysis of clinical data of patients hospitalized for the first time for allograft renal transplantation or simultaneous pancreas-kidney transplantation at the Organ Transplantation Center of the Second Affiliated Hospital of Guangzhou Medical University from January 2020 to March 2021,with 2-year follow-up,including patient gender,age,whether delayed graft function occurred,presence of acute rejection,surgical procedure,immuno-inducing regimens,maintenance immunosuppressive regimen,transplanted kidney biopsy pathology,BKV antibodies(include IgG,IgM,and IgA)titers in the time periods,including pre-transplantation and the first month,third month,sixth month and one year of post-transplantation.And the maximum blood and urine BKV DNA load values from the first to third month,third to sixth month,sixth to twelfth month and the first to second year after transplant surgery.Based on BKV blood and urine DNA load and renal puncture biopsy pathology,they were divided into urinary BKV+ group,urinary BKV-group,blood BKV+ group,blood BKV-group,BKVAN+ group and BKVAN-group.Data from the Continuous normal distribution were expressed as mean standard deviation and data from the continuous skewed distribution were described by median M value and interquartile range spacing(P25,P75).BKV antibody positive rates and titers(IgG,IgM,IgA)were analysed using SPSS25.0 software,and comparison of means between positive and negative groups was carried out by independent samples T test,and rate comparison was performed by Chi-square test or Fisher’s precision probability test The Mann-Whitney U test was used to compare differences in antibody titers between the positive and negative groups,and Kaplan-Meier survival analysis of the time series of events was carried out using Graph Pad Prism 9.0 and tested with Log-rank test and P< 0.05 was considered to be statistically significant.Receiver operating characteristic curve(ROC)were plotted using the R(4.0.5 Version)for statistically significant findings,and the diagnostic value of each index was analyzed for the area under the curve(AUC).【RESULTS】A total of 223 patients were included in the study,with 127 urinary BKV-,96 urinary BKV+,21 blood BKV+,and 202 blood BKV-post-transplantation.31 patients underwent transplanted kidney biopsy pathology,of whom 10 were BKVAN+and 21 were BKVAN-.1.The serological status of pre-transplant recipients’ BKV antibodies(IgG,IgM,IgA)is not related to the time to first post-transplant BK viruria,viremia,and BKVAN(P >0.05).2.Preoperative BKV IgG,IgM,and IgA antibody titers were not significantly different in the urinary BKV+ and urinary BKV-groups(P >0.05).Postoperative BKV IgG antibody titers at 6 months were significantly higher in the urinary BKV+group than in the urinary BKV-group at the subsequent occurrence(P=0.005).Postoperative BKV IgM antibody titers at January,March,and June were significantly higher in the group with subsequent occurrence of urinary BKV+ than in the urinary BKV-group(P1<0.001,P2=0.008,P3=0.001).Postoperative BKV IgA antibody titers were significantly higher in the urinary BKV+ group than in the urinary BKVgroup at first month and sixth months after surgery(P=0.020,0.016).3.Postoperative BKV IgM antibody titers at January and June were significantly higher in the group with subsequent occurrence of blood BKV+ than in the group with blood BKV-(P=0.039,0.001).BKV IgA antibody titers at the sixth months after transplantation were significantly higher in the group with subsequent occurrence of blood BKV+ than in the group with blood BKV-(P=0.009).4.postoperative BKV IgG antibody titers at January and June were significantly higher in the BKVAN+ group than in the BKVAN-group at subsequent occurrence(P=0.046,0.002).Postoperative 6-month BKV IgM antibody titers were significantly higher in the group with subsequent occurrence of BKVAN+ than in the BKVANgroup(P=0.001).5.ROC curve analysis showed that the optimal cut-off value for the first month post-transplantation to predict subsequent urinary BKV+ was 0.130,with a sensitivity and specificity of 0.784 and 0.578,respectively,and AUC is 0.718.The optimal cut-off value for sixth month after transplantation of BKV IgM antibody titer to predict subsequent from sixth to twenty-forth month urinary BKV+ was 0.354,with a sensitivity and specificity of 0.458 and 0.947,respectively,and AUC is 0.741.The optimal cut-off value for postoperative BKV IgA antibody titers at the first month to predict subsequent urinary BKV+ within two years was 0.046,with a sensitivity and specificity of 0.865 and 0.422,respectively,and AUC is 0.640.The optimal cut-off value for postoperative BKV IgM antibody titers at the first month to predict subsequent blood BKV+ at 2 years was 0.712,the sensitivity and specificity were0.600 and 0.990,respectively,and the AUC is 0.775.The optimal cut-off value for predicting the subsequent 6-24 months of blood BKV+ by the sixth month of postoperative BKV IgA antibody titer was 0.174,with a sensitivity and specificity of0.800 and 0.934,respectively,and the AUC is 0.849.【Conclusions】1.The time to first positive BKV viruria,viremia and BKVAN in kidney transplant recipients post-transplantation is not related to the recipient’s BKV antibody serological status pre-transplantation.2.BKV IgG,IgM and IgA antibody levels in kidney transplant recipients were increased before the onset of BK viruria,BK viremia and BKVAN,especially in the case of BKV IgM antibody levels.3.BKV IgM antibody may be a good predictor of BKV infection in kidney transplant patients.