BK Virus Infection Research Articles

Usefulness of pre- and post-transplant BK virus-specific ELISPOT assay for predicting the outcome of BK virus infection in kidney transplant recipients

Usefulness of pre- and post-transplant BK virus-specific ELISPOT assay for predicting the outcome of BK virus infection in kidney transplant recipients

Incidence and risk factors of kidney allograft loss due to BK nephropathy in the pediatric population: A retrospective analysis of the UNOS/OPTN database.

BK virus infection can lead to graft dysfunction and loss in kidney transplant recipients. Risk factors for BKV and BKVN have been inadequately studied in children. Here, we evaluate the incidence and risk factors of allograft loss due to BKVN in the pediatric population of the UNOS data set. We conducted a retrospective cohort analysis of the UNOS database and identified all pediatric recipients of kidney transplantation between 2000 and 2018. We compared donor and recipient characteristics, including cause of ESRD, among patients who lost their graft due to BKVN or other causes, and those with functioning allograft. Kaplan-Meier curve and Cox regression analysis were performed to evaluate the risk factors. A total of 66 patients (0.47%) suffered graft failure from BKVN. Older age, male gender, HLA mismatch, and rejection at 1year were significantly associated with BKVN graft failure, compared to recipients with functioning allograft. In comparison with graft loss due to other causes, male gender, higher HLA mismatch, rejection in 1st year and tacrolimus use at discharge were significantly associated with BKVN graft loss. Recipients who received mycophenolate at time of discharge were at reduced risk for BKVN graft failure. Compared to graft failure from other causes, BKVN graft failure had shorter death censored graft survival [P=.001]. ESRD due to urologic causes and Alport syndrome had higher rate of BKVN graft failure. Incidence of graft loss from BKVN in the pediatric population was 10.2 per 10000 patient-years in this study. BKVN is associated with early allograft failure in the pediatric population, compared to other causes of graft loss. Male gender, HLA mismatch, rejection in 1st year, and urological cause of ESRD are risk factors for graft failure from BKVN in children.

Safety and Efficacy of Virus-Specific Cytotoxic T-Lymphocytes Manufactured By the IFN-g Cytokine Capture System for the Treatment of Refractory Adenovirus, Cytomegalovirus, Epstein Barr Virus, and BK Virus Infections in Children, Adolescents and Young Adults after Allogeneic Hematopoietic Stem Cell Transplantation, Solid Organ Transplantation, or with Primary Immunodeficiency (IND# 17449)

Background: Viral infection remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) (Bollard/Heslop Blood 2016). Anti-viral agents for treatment of viral infection in immunocompromised patients are limited in efficacy and are associated with significant toxicities (Gerdemann BBMT 2004; Sili Cytother 2012). The use of virus-specific cytotoxic T-lymphocytes (VST) for immunocompromised patients with viral infections has been associated with therapeutic benefit and improved OS (Bollard/Heslop Blood 2016; Sutrave Cytother 2017). Methods of VST production include ex-vivo expansion and direct selection (Gottlieb Cytother 2017). Ex-vivo expansion requires prolonged manufacturing time, is associated with T-cell exhaustion, and results in a limited donor pool. Direct selection is rapid (12-24 hours), can be done locally, allows for expanded HLA matching, permits a low degree of HLA match to the recipient, and can be adapted for many viruses. A multicenter consortium, the Viral Cytotoxic T-Lymphocyte Consortium (VIRCTLC) was created to investigate the safety and efficacy of VST manufactured by direct selection using the IFN-g Cytokine Capture System process automated on the CliniMACS® Prodigy device (Miltenyi Biotec) for immunocompromised patients with viral infection (Figure 1). Objective: Determine the safety and efficacy of VST for the treatment of immunocompromised child, adolescent and young adult (CAYA) patients with refractory, systemic viral infection and/or viral infection and intolerance to appropriate anti-viral medical therapy. Design/Methods: CAYA patients after allo-HSCT, solid organ transplantation (SOT), or with primary immunodeficiency (PID) with refractory adenovirus (ADV), cytomegalovirus (CMV), Epstein Barr virus (EBV) or BK virus (BKV) infections as evidenced by increasing serum RT-PCR DNA (by 1 log) after 7 days or persistent quantitative RT-PCR DNA copies after 14 days of appropriate anti-viral therapy, and/or known resistance to anti-viral agents, and/or intolerance to anti-viral agents were eligible. Related donors with ≥1 HLA A, B, or DR match to recipient and with an adequate T-cell response to virus specific MACS® PepTivators were eligible. Donors were screened with viral specific antigen (PepTivator®) to predict successful VST manufacturing. Peripheral blood mononuclear cells (PBMC) were collected from eligible related donors using non-mobilized apheresis. VST were isolated using the CliniMACS® Prodigy following stimulation of PBMC with specific viral MACS PepTivator® pools, generously provided by Miltenyi Biotec. Production of CD4+ and CD8+ VST was performed as previously described (Feuchtinger Blood 2010). The target cell dose was 0.5x104 CD3+/kg for HLA mismatched haploidentical related donors and 2.5x104 CD3+/kg for matched related donors. Based on response and safety, VST were given every 2 weeks for a maximum of 5 infusions. Results: Eleven patients have been enrolled to date. Seven patients were treated for ADV, 2 for BKV, 1 for CMV, and 1 for EBV. There were 8 males and 3 females enrolled, aged 1-38 years. There were 10 patients post allo-HSCT and 1 patient post SOT. There were 8 haploidentical, related, original allo-HSCT donors and 3 haploidentical, related, third party donors. There have been no matched related donors enrolled to date. The mean±SEM %CD4+ IFN-g+ of total CD4+, %CD8+ IFN-g+ of total CD8+, and %CD3 cells recovered in the final product were 21.5±4.8, 25.0±7.0, and 50.4.2±7.2, respectively. The median number of VST infusions was 2 (1-5). The mean±SEM CD3+ cell dose was 0.49±0.001x104. Ten patients achieved complete response (PCR negative) and 1 patient achieved partial response (PCR≥1 log decrease). The overall response and complete response rates were 100% and 90.9%, respectively. The median time to maximal response was 34 days (7-141) (Table 1). No patient developed aGVHD, cGVHD, infusion reaction or CRS associated with VST. Conclusion: Preliminary results of this pilot study demonstrate that VST are safe, well tolerated and efficacious in CAYA with refractory viral infections after allo-HSCT, SOT or with PID. Manufacturing utilizing the CliniMACS® Prodigy device is rapid, reproducible and effective. Accrual is ongoing. This research is supported by FDA RO10063-01A1. Disclosures Flower: Lentigen Technology Inc/Miltenyi Biotec: Research Funding. O'Donnell:Kiadis Pharma: Other: Licensing of intellectual property. Lee:Kiadis Pharma Netherlands B.V: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Johnson:Cell Vault: Research Funding; Miltenyi Biotec: Research Funding. Cairo:Technology Inc/Miltenyi Biotec: Research Funding; Nektar Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Miltenyi: Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Investigating Risk Factors for the Development of BK Virus Infection in Kidney Transplant Recipients in Guilan Province during 2007-2015.

Polyomavirus nephropathy has been recognized as an important cause of silent loss of kidney transplant function in up to 50% of kidney recipients (1). The present study aimed to evaluate the risk factors associated with BK virus infection in kidney transplant recipients. Clinical information, urinary Decoy cells, and blood polymerase chain reaction (PCR) tests were collected for polyomavirus infection in 223 kidney transplant recipients undergoing surgery at Razi hospital at Guilan University of Medical Sciences between 2007 and 2015. Kidney biopsies were performed in patients with BKPyV- DNAemia more than 10,000 Copies/ml or increased plasma creatinine. Among 223 patients, 116 (52%) were male. The mean age of participants was 49.57±13.48 years. Out of 223 participants, 41 (18.4%) had Decoy cells in their urine, and 182 (81.6%) did not, 15 of whom (6.7%) had viral genome in their blood. Only did 3 patients out of 10 have BK Virus nephropathy in their kidney biopsy. Among risk factors, it was found that post-transplant duration (P< 0.001) and the use of anti-thymocyte globulin (P= 0.001) were the most significant risk factors for finding decoy cells in patients' urine. Post-transplant time, particularly the first 6 months, was found as the most important risk factor for the reactivation of polyomavirus infection in our patients because of strong immunosuppression and use of anti-thymocyte globulin (for prophylaxis or rejection treatment). It is concluded that kidney transplant recipients should be monitored in episodically after transplantation.

Resolution of a High Grade and Metastatic BK Polyomavirus-Associated Urothelial Cell Carcinoma Following Radical Allograft Nephroureterectomy and Immune Checkpoint Treatment: A Case Report

BackgroundBK viral infection in the posttransplant setting continues to cause serious morbidity with effects ranging from allograft nephropathy and dysfunction to urothelial malignancy. ResultsIn this report, we present a patient that developed BK-associated nephropathy and, 6 years later, locally advanced urothelial malignancy in the renal allograft with nodal, muscle, and extremity involvement. Following radical allograft nephroureterectomy, he was treated with palliative radiation and the immune checkpoint inhibitor atezolizumab. Follow-up imaging at 1 year demonstrated radiographic complete response. ConclusionsThis report supports the growing body of evidence supporting the association of urothelial malignancy and BK virus infection in renal transplant recipients. Further, it highlights the novel application of immune checkpoint inhibitors in the treatment of advanced posttransplant malignancy, in particular when the allograft is removed and the tumor is possibly of donor origin.

Characterization of aberrant pathways activation and immune microenviroment of BK virus associated nephropathy.

In the context of transplantation with the use of immunosuppressive drugs, BK virus infection has become the main cause of BK virus nephropathy(BKVN) in renal transplant recipients(KTRs). More importantly, BKVN may cause further allograft dysfunction and loss. However, the role of the immune microenvironment in the pathogenesis of BKVN remains unknown. Therefore, we collected microarray data of KTRs to elucidate the immune characteristics of BKVN. Via the CIBERSORT, we found that BKVN had relatively more activated memory CD4 T cells. Immunostaining showed that CD4+ and CD8+cells were significantly different between BKVN and stable allografts(STAs). In addition, the expression of immune-related genes(antigen presentation, cytotoxicity, and inflammation) was significantly higher in BKVN than in STAs. The results of gene set enrichment analysis(GSEA) and single-sample GSEA(ssGSEA) indicated that immune cell-,cytokine-,chemokine-, and inflammation-related pathways were significantly activated in BKVN, while metabolism- and renal development-related pathways were significantly downregulated in BKVN. In addition, the immune microenvironments of the peripheral blood in patients with BK viremia(BKV) or transplant kidney biopsy(TKB) with BKVN may be different. Overall, the immune microenvironment may play important roles in the occurrence and development of BKVN and provide a theoretical basis for preventing the occurrence of BKVN and finding novel treatments.

Update on the Management of BK Virus Infection.

The BK polyomavirus was isolated in 1971; it has been a significant risk factor for both graft dysfunction and failure in renal transplant recipients. So far, no specific treatment option has been available for effective treatment or prophylaxis for BK virus infections. Although the use of heavy immunosuppression has been the main risk factor for BK virus infection, other risk factors are equally important, including elderly recipients, prior rejection episodes, male sex, human leukocyte antigen mismatching, prolonged cold ischemia time, pretransplant BK virus serostatus, and ureteral stenting. Regular follow-up for BK virus infections according to each institution's policy has been, so far, effective in detecting patients with BK virus viremia and consequently preventing allograft loss. The mainstay of management continues to be reduction of immunosuppression. However, newer options are providing new insights, such as cellular immunotherapy. In this review, we will address the diagnosis, screening, new diagnostic tools, and updated management of BK virus infections.

P1649IS BK VIRUS CARCINOGENIC?!

Abstract Background and Aims The role of polyomaviruses (PyV) in malignancy is controversial, this can be demonstrated in three ways; Firstly, hit and run mechanism where polyomaviruses contribute to the early phases of oncogenic progression. The second way, where PyV act as a passenger as polyomaviruses neither necessary nor contribute to the oncogenic progression. The third way, where PyV acts as (bystander) as PyV is not related to the malignancy, but PyV could be detected in the anatomically connected sites or neighbouring cells. BKV has been classified as a possible carcinogenic to humans (2b) as there is sufficient evidence that it is carcinogenic to animals, however, BKV carcinogenicity evaluation to humans was inadequate. There are inconsistent data regarding the contribution of BKV to tumors that occur in both animals and humans. Method Retrospective analyses of 492 consecutive renal transplant recipients in a single-center, 2010-2018. Data Source: prospectively managed electronic patient records. Malignancy data in both control and BKV infected groups were assessed. Results A total of 492 cases were studied, were categorized into 2 groups the BKV infected group (n:73) patients and BKV non-infected group (n: 419) patients, then an assessment of different malignancies in both groups. The BKV infected group had 15 cases out of 73 who had malignancy, while the BKV non-infected group had 28 cases out of 419 totally (Table 1). The association between malignancy in BKV was statistically significant (P-value of 0.038). Moreover, the risk factors involved in the development of malignancy in renal transplant recipients were older age, BK virus infection and maintenance immunosuppression agents (Table 2). Lastly, Logistic regression analysis was used to assess predictors of malignancy among renal transplant recipients. For every one-year increase in age among renal transplant recipients, the odds of having a malignancy increase by 4.6% (p=0.003). Meanwhile, there is a 4 times increase in the odds of having malignancy for recipients who are BK virus-positive vs. those who are BK virus negative (p=0.001). Furthermore, there is a 10 times increase in the odds of having malignancy for recipients who are on sirolimus as a maintenance immunosuppressant vs. those who are on TAC/PRED/MMF (p=0.007). Conclusion Our study highlights the statistically significant correlation between BK virus infection and the development of malignancy in renal transplant recipients. However, statistical correlation doesn`t mean causation which makes the potential oncogenic role of BKV is unclear. Also, there is increased reporting of malignancy in patients infected with BKV. Increased vigilance is required for early detection of malignancy in patients infected with BKV not only the patients who are heavily immunosuppressed.

P1766EFFECT OF EVEROLIMUS AND REDUCED CALCINEURIN INHIBITORS ON BIOPSY PROVEN BK VIRUS ASSOCIATED NEPHROPATHY-

Abstract Background and Aims BK virus-associated nephropathy (BKVAN) is a clinically important entity that results in an allograft loss in kidney transplant recipients (KTRs). Mammalian target of rapamycin inhibitors (mTOR-i) have been proposed as possible immunosuppressive therapy in BK virus infection because of their antiviral capacity. However, the effect on biopsy (bx) proven BKVAN is still unclear. Method This a retrospective single center review of 27 (KTRs) on triple immunosuppression regimen (CNI/MMF/prednisone), who developed BK viremia and had bx proven BKVAN (n=13, 48%). Patients were converted to Everolimus, reduced/or no CNI and prednisone. We present the renal allograft function, BK viremia status and histological data after a mean follow up period of 28.4±17.9 months post-transplant. Results We reviewed 27 KTRs (17 males, 11 AA) transplanted between 2012 and 2019, who developed BK viremia, 23/27 patients (85%) underwent surveillance &amp; for cause bx (n=55). All patients were switched to Everolimus, reduced CNI (one patient was on Cyclosporin) and prednisone regimen. Median time from transplant to BK viremia was 2.5 months (min 0.7-max 76.7). After a mean follow up period of 17.9±12 months post conversion, the mean serum creatinine remained relatively stable (1.54 mg/dl ±0.47; 1.79 mg/dl±0.82; P=0.17). The mean BK viral load was statistically significantly reduced (P=0.045), pre/post conversion median BK levels were (35900 (655-2.5 million copies) and 752 (0-92150) respectively), 13/27 (48%) patients had undetectable BK viral load. 13/27 (48%) had bx proven BKVAN, with 4/13 (31%) had no follow up bx, 4/13 (31%) had follow up bx proven resolved BKVAN and 5/13 (38%) had bx proven persistent BKVAN (figure 1). Post conversion 3/27 (11%) patients were treated for borderline acute cellular rejection with pulse steroids and had negative DSA. Conclusion Conversion to mTOR-i-based therapy could provide an added benefit in BK viremia as well as BKVAN and could be an effective strategy for the decrease of the viremia and increase of graft survival in selected patients. In the medium-term follow up, the BK viral load was statistically significantly lower even in bx proven persistent BKVAN, and almost half (4/9) of the bx proven BKVAN have resolved. The median time for conversion for patients with resolved BK nephropathy was 25 days (range 19-38) vs 263 days (range 17-931) in patients with persistent BK nephropathy (P&amp;lt;0.001), pointing to possible benefit of rapid conversion to mTOR-i based regimen in the setting of BK viremia.

P1819PEDIATRIC KIDNEY TRANSPLANTATION IN INDIA :IMPROVING OUTCOMES

Abstract Background and Aims Renal transplantation is the modality of the choice for the management of children with end stage renal disease. It offers better quality of life, though associated with risk of rejection and infection. This study was conducted Method This is a retrospective review of patients &amp;lt;= 18 years of age who underwent renal transplant at Fortis hospitals, India from 2006 to 2019.The choice of induction agent was based on the discretion of the treating team and the socioeconomic tests of the patient, All these children were treated with Tacrolimus, MMF and prednisone, At each visit they were subjected to standard haematological and biochemical tests Data on age, sex, use of immunosuppression, incidence of infection and rejection was collected. Percentage, range and median were used to represent the data. Results The study group comprised of a total 120 pediatric patients underwent renal transplant between 2006-2018 at Fortis hospitals. Median age was 14 years (3-18 years) and 85 were boys and 35 were girls. The immunosuppression protocol consisted of induction by either basiliximab or ATG, followed by maintenance immunosuppression with tacrolimus, mycophenolate and steroids. 17 patients received no induction. Median creatinine at the time of discharge was 0.74 mg/dl (0.3-1.6 mg/dl). The median duration of follow up was 60 months (1-156 months). In our cohort, patient survival rate was 97.9 % and graft survival rate was 94.6 %. 18 patients had infections - UTI (8), CMV infections (7), BK virus infection (2), tuberculosis (1), varicella (1), cryptosporidium diarrhea (1) and fungal infection (1). Rate of rejection was 13.3%. Two patients had graft loss in the early post operative period, one secondary to renal vein thrombosis and other due to BK virus infection/acute tubular necrosis. Five patients lost the graft over the next 12 years due to non compliance with medications (4) and recurrence of FSGS (1). 2 patients died with functioning graft, one due to severe pancreatitis and other due to severe sepsis. One died after return to dialysis. Conclusion With advances in immunosuppression, rejection rate and graft survival have improved dramatically over the last decade. Compliance with medications and regular follow up are the major contributors for satisfactory long-term outcome.

P1724RISK FACTORS FOR BK VIRUS INFECTION AFTER KIDNEY TRANSPLANTATION IN THE CONTEMPORARY ERA: A SINGLE-CENTRE OBSERVATIONAL STUDY

Abstract Background and Aims BK infection remains a risk factor for kidney transplant dysfunction and allograft loss. While many risk factors are reported in the literature, many are from historical cohorts and have never been validated in the contemporary era. The aim of this study was to explore risk factors for BK virus infection in the contemporary era of kidney transplantation and immunosuppression using a well-phenotyped clinical cohort. Method In this single-centre observational study, data was extracted from hospital informatics systems for all kidney allograft recipients transplanted between January 1st 2007 and June 30th 2018. BK virus was checked in the context of any transplant dysfunction (indication-based) aligned with UK guidance. Positive BK virus results were defined as &amp;gt;200 copies/ml. Clinical outcomes extracted from electronic hospital records were linked with national datasets. Univariate analysis was undertaken to investigate the association between donor-, recipient- and transplant-related variables and risk for BK virus reactivation. Any variable with a p-value &amp;lt;0.15 in univariate Results Data was analysed for 1,770 kidney transplant recipients with median follow up 5.3 years (IQR 2.7 to 8.7 years). BK virus was associated with (versus without); male sex (8.3% versus 5.3% respectively, p=0.010), ABO-incompatible transplantation (12.7% versus 5.9% respectively, p=0.021) and delayed graft function (9.0% versus 6.3% respectively, p=0.032). In a multivariate analysis, including all variables in univariate analysis with p-value &amp;lt;0.15, the only independent variables associated with BK infection were recipient male sex (OR 2.051 [95% CI 1.196-3.519], p=0.009 and ABO-incompatible transplantation (OR 4.087 {95% CI 1.847-9.042], p=0.001). From an outcome perspective, recipients with BK viraemia had worse graft function at 1-, 3- and 5-year post kidney transplantation but no increased risk for death-censored graft loss. Conclusion In the contemporary era, only recipient male sex and ABO-incompatible kidney transplantation are independently associated with risk for BK infection. Study limitations include lack of data regarding novel risk factors (e.g. BK virus serostatus). Association does not imply causality and we suggest further work is warranted to validate contemporary risk factors for BK infection in different kidney transplant population cohorts.

Clinical Characteristic and Outcomes of BK Virus Infection in Kidney Transplant Recipients Managed Using a Systematic Surveillance and Treatment Strategy

BackgroundBK virus (BKV)–associated nephropathy is a significant complication of kidney transplantation that progresses to graft dysfunction and graft loss. The aim of this study was to know the infection rate and progression of BKV according to our strategy. Materials and MethodsThis study included 302 patients who received kidney transplantation between August 2010 and October 2012. Patients were divided into 4 groups: no BK infection, BK viruria only, low BK viremia, and high BK viremia. ResultsIn this study, 57 patients had BK viremia (18.9%), and 18 patients had BK nephropathy (5.9%) during a 2-year follow-up period. Age, sex, cytomegalovirus (CMV) viremia, existence of donor-specific antibodies, type of transplantation, and delayed graft function were not significantly different. Disappearance of BKV infection was better in the viruria and low viremia groups than in the high viremia group (P = .001), and duration of BK infection was longer in the high viremia group than the low viremia group (P = .002). ConclusionAll diagnosed cases of BKV nephropathy were in the high BK viremia group. For BK viruria and viremia, early detection of BK infection together with early intervention by reduced immunosuppressant is a useful strategy to maintain allograft function. Long-term follow up is required to identify the risk factors for BK infection and graft survival after kidney transplantation.

Impact of Kidney Donor Profile Index Scores on Post-Transplant Clinical Outcomes Between Elderly and Young Recipients, A Multicenter Cohort Study

We investigated if clinical outcomes after kidney transplantation (KT) from deceased donors (DDs) with high Kidney Donor Profile Index (KDPI) can be different according to the age of KT recipients (KTRs). Six-hundred fifty-seven KTRs from 526 DDs were included from four transplant centers. We divided KTRs into elderly-KTR and young-KTR groups based on age 60 and each group was subdivided into high- or low-KDPI subgroup based on KDPI score of 65%. We compared short-term and long-term clinical outcomes among those four subgroups (low KDPI-young KTR, low KDPI-elderly-KTR, high KDPI-young-KTR, high KDPI-elderly-KTR). In short-term outcomes including acute rejection, BK virus and CMV infection, there was no significant difference among the four subgroups. In the long-term outcomes, the development of cardiovascular disease was higher in the high KDPI-elderly-KTR group than the other groups. In comparison of allograft survival rate, the high KDPI-young KTR subgroup showed highest risk for allograft failure and there was significant interaction between high-KDPI donors and young-KTR on allograft survival rate (P = 0.002). However, there was no significant difference in comparison of the patient survival rate. In conclusion, clinical impact of high-KDPI in DDs on post-transplant allograft survival may be less significant in elderly-KTR than in young-KTR.

Pure Red Cell Aplasia and Antibody-Mediated Rejection: Double Trouble in 1 Kidney Transplant Recipient Solved by Intravenous Immunoglobulin Infusion: A Case Report

Acquired pure red cell aplasia (PRCA) is characterized by severe normocytic (rarely macrocytic) and normochromic anemia, a low reticulocytes count in peripheral blood, and near absence of erythroid precursors in the bone marrow, with a normal level of erythropoietin. We describe a case of the kidney transplant recipient, diagnosed with PRCA induced with parvovirus B19 infection. Our case demonstrates that although this complication is rare, it should be considered in a differential diagnosis of anemia diagnostics in immunocompromised patients. In our case reduced immune response resulted from post-transplant immunosuppressive therapy. In our patient, apart from infection by parvovirus B19, graft dysfunction due to polyomavirus BK virus infection was also detected together with histologic and serologic features of antibody-mediated renal graft rejection. Considering the entire clinical picture, intravenous immunoglobulin therapy (IVIg) was successfully introduced.

Usefulness of BK virus-specific interferon-γ enzyme-linked immunospot assay for predicting the outcome of BK virus infection in kidney transplant recipients.

Background/AimsTo investigate if BK virus (BKV)-specific T cell immunity measured by an interferon-γ enzyme-linked immunospot (ELISPOT) assay can predict the outcome of BK virus infection in kidney transplant recipients (KTRs). MethodsWe included 68 KTRs with different viremia status (no viremia [n = 17], BK viremia [n = 27], and cleared viremia [n = 24]) and 44 healthy controls (HCs). The BK viremia group was divided into controller (< 3 months) and noncontroller (> 3 months) according to sustained duration of BKV infection. We compared BKV-ELISPOT results against five BKV peptides (large tumor antigen [LT], St, VP1-3). ResultsBKV-ELISPOT results were higher in three KTRs groups with different BKV infection status than the HCs group (p < 0.05). In KTR groups, they were higher in cleared viremia group than no viremia or BK viremia group. Within the BK viremia group, controller group had higher LT-ELISPOT results compared to noncontroller group (p = 0.032). Also, KTRs without BK virus-associated nephropathy (BKVN) had higher LT, St, VP1, and VP2-ELISPOT results than those with BKVN (p < 0.05). ConclusionsBKV-ELISPOT assay may be effective in predicting clinical outcomes of BKV infection in terms of clearance of BK virus and development of BKVN.

Prevalence of BK Virus Infection in a Large Heart Transplant Population

In heart transplant (HT) patients, prevalence of BK virus (BKV) infection and its clinical significance are unknown. We sought to understand rates of BKV infection in a large HT cohort and to evaluate risk factors and effects of infection. Consecutive HT patients at a single institution were evaluated for BKV infection in blood and urine in the 1st year post-transplant. Titers were collected 1-month post-transplant and then every 6 months, with additional testing if needed. Rates of infection were compared between HT and combined organ transplant. In the HT group, patients with no infection, viruria with no viremia, and viremia with or without viruria were compared. Measures of immunity and kidney function were collected with titers in blood to evaluate Spearman rank correlations using log10 transformation. 104 patients were enrolled: 89 HT, 12 heart/kidney transplant (HKT), 1 heart/liver transplant, 2 heart/liver/kidney transplant. Viruria and viremia were highly prevalent in HT (42% and 30%, respectively). Compared to HT patients without infection, those with viremia were older (57.8 vs 50.8 yrs, p=0.04), and tended to have lower pre-transplant glomerular filtration rate (GFR) (63.3 vs 71.4 mg/dL/1.73m2, p=0.14). There were no significant differences between patients with viruria compared to viremia. 1-year freedom from viruria was 55% in HT vs 46% in HKT. 1-year freedom from viremia was 67% in HT vs 56% in HKT (Figure). Viremia titers in HT strongly correlated with immunoglobulin (IgG) levels (R= -0.60, p=0.001), but not other immunity measures. Viremia titers were not correlated with GFR (R= 0.05, p=0.70). When comparing GFR before transplant to 1-year post-transplant, there was no significant difference found in the groups with no infection, viruria, and viremia (-22.4 vs -23.7 vs -23.4 mg/dL/1.73m2, p=0.98). BK viremia is very common in HT patients. BK viremia correlated with IgG, but not kidney function. Longer surveillance studies are needed to evaluate effects of BKV infection.

Treatment of BK Virus Infection With CTL Cells in Immunocompromised Transplant Patients

Treatment of BK Virus Infection With CTL Cells in Immunocompromised Transplant Patients

SUN-363 GUT MICROBIOTA DISTURBANCE IN KIDNEY TRANSPLANTATION

Gaining long-term graft function and patient survival remain a critical challenge following kidney transplantation. Recently, it is reported that microbiota is associated with complications in kidney allograft recipients. Therefore, we conducted a study in a kidney transplant population which aimed to: To describe the epidemiologic characteristics of our population, to identify the factors that could influence the microbiota and to delineate the risk factors associated with microbiota and could affect the allograft outcome We conducted a cross sectional study carried out by the nephrology department in the university hospital of Sousse Sahloul from November 2007 to September 2015. We included in our study patients who received tacrolimus in maintenance therapy. In the absence of the current possibility of direct study of the microbiota we considered that infectious complications requiring the use of several antibiotics were responsible for microbiota change in renal transplant patients. Over the study period, 170 kidney transplant were performed and 81 patients (47%) were included in the study of the total transplanted patients. The average age of the adults was 32.84±9,176 [17 - 55] years while the mean age of the children was 12.95±2.91 [7 - 16] years. The sex ratio was 1.5. The average age of kidney donors was 38.68 ± 10.607 years. Renal transplantation was performed from a cadaveric donor in 4 cases and in 77 cases it was from a living donor. The induction therapy for kidney transplant recipients was based on the antithymocyte immunoglobulin in 60% of cases and the anti-interleukin-2 receptor antibodies in 40 % of cases. The mean initial dose of tacrolimus was 8.52 ± 1.9 mg/d which corresponds to 0,17 ± 0.065 mg/kg/d. Infectious complications were observed in 66 patients (82.7%). Among our patients, 52 patients had urinary tract infection, 23 patients had BK virus infections,16 patients had gastrointestinal infection, 14 patients had cytomegalovirus infection, 6 patients had Candidiasis and 5 patients had a common germ pulmonary infection. In our series, 11 patients (13.6%) presented allograft dysfunction during their follow-up, 5 patients (6.2%) had lost their allograft and 5 patients (6.2%) have died. The comparative analysis revealed that dose weight of tacrolimus at the first year was significantly associated with the infectious complications. In fact, the patients who had infectious complications required higher doses of tacrolimus at first year (p=0.028). We found that patients who had two or more infections were exposed to more risk of allograft rejection (p=0.006). We found that patients who had at least two infections presented an unfavourable outcome (p=0.026). We noted that the antithymocyte immunoglobulin was associated with a higher risk of infections (p=0.035) than basiliximab (p=0.026). Renal transplantation is an effective treatment for an end-stage kidney disease, however, post-transplant complications remain its major challenge. A deeper understanding of the function and composition of microbiota can help clinic to connect the microbiota features with the organ outcomes, including graft survival, inflammation, infection, rejection, alloreactivity and fibrosis.

SAT-339 Low Dose Induction Immunotherapy with Anti Human T-lymphocyte Immunoglobulin (Grafalon) in High Risk Renal transplantation – A Real-world, Single Centre Experience from India

The current armamentarium of rabbit polyclonals includes thymoglobulin and Grafalon. The experience with the latter has been quite limited as until recently it was not available in India. In addition, its dose and duration are controversial, differs center-wise, and is based on scarce clinical data. The objective of this study was to assess the safety and efficacy of Grafalon induction in live related high-risk kidney transplant patients. (history of blood transfusions, HLA mismatch> 3). This was a single-center, prospective, observational study of 54 renal transplant patients who received Grafalon as induction therapy. All patients underwent living donor kidney transplantation. Pre-transplant CDC and flow crossmatch were negative in all. Grafalon was administered at an average dose of 6.0 mg/kg body weight, as a single dose infusion through peripheral intravenous line over 3 hours on day 0. Tacrolimus, MMF and prednisolone constituted maintenance immunosuppression in all patients. These patients were followed up twice a week for 1 month, once a week for 2nd month and once in 15 days for the 3rd month and thereafter once a month. At each visit, they were evaluated clinically as well subjected to laboratory investigations. Tacrolimus levels were monitored twice a week for the first week, once a week for the first month and thereafter once a month. Microsoft Excel was used to analyse the data. All of the patients tolerated Grafalon infusion well and there were no major infusion reactions or fever requiring temporary stoppage or cessation of the drug. Seven patients (13%) developed biopsy proven acute rejection. Majority of them were mild grade cellular rejections and responded well to steroids with good recovery of renal function. At a mean follow up of 10.65+5.4months, patient survival was 100% and graft survival was 100%. Infection episodes were seen in 7 patients with UTI (n=6) being the commonest cause. There were no documented CMV or BK virus infections. Post-transplant, day 1 serum creatinine was 4.89+2.78 mg/dL which reduced to 1.44 ± 0.8mg/dL (n=49, p<0.0001) at day 10 and 1.24 ± 0.35 mg/dl (n=34, p<0.0001) at day 30. Grafalon (6mg/kg) is associated with an acceptable efficacy and safety profile in renal transplantation. Larger studies are necessary to confirm the findings.

SUN-348 Risk Factors for the Development of BK Virus Infection in Kidney Transplant Recipients in Gilan Province During 2007-2015

SUN-348 Risk Factors for the Development of BK Virus Infection in Kidney Transplant Recipients in Gilan Province During 2007-2015