BK Virus Viremia Research Articles

Intravenous Human Immunoglobulin in the Treatment of BK Virus Nephropathy in Kidney Transplant: A Case Report

The BK virus infection is common in the immunocompetent population and is asymptomatic in the majority of cases. However, in renal transplant patients, reactivation and replication can occur, leading to the development of BK virus-associated nephropathy (BKVN), which is associated with renal injury and graft loss. The objective of this case report was to demonstrate a case of BKVN that showed a good response to the use of human immunoglobulin. A 37-year-old man who underwent a second transplant received rabbit-derived anti-thymocyte human immunoglobulin at a dose of 6mg/kg intravenously as induction immunosuppressive therapy, and maintenance therapy with tacrolimus, prednisone, and mycophenolate sodium (MFS). At 3 months post-transplant, he presented sustained BK virus viremia (70,000-100,000 copies/mL), leading to a reduction in the dose of MFS and tacrolimus. A biopsy diagnosed BKVN class 2/B2, and viremia increased to over 1 million copies/mL at 22 months, prompting the discontinuation of tacrolimus without response. Intravenous human immunoglobulin (IVIG) was administered at 2g/kg at 22 months and again at 33 months, with viremia peaking at 2 million copies three months later. However, it steadily declined to 5,500 copies/mL at 52 months post-transplant. Currently, the only proven therapy for BKVN is the reduction of immunosuppression. However, in patients who do not respond, IVIG is considered as an option, with good results demonstrated in case reports, as shown here. Nevertheless, the data are based on case reports or case series, and the development of controlled clinical trials is necessary for confirmation of the efficacy.

Tacrolimus Intrapatient Variability on Graft Outcomes inAdherent Renal Transplantation Patients: A Cross-SectionalStudy.

Tacrolimus is the mainstem of immunosuppressive therapy in kidney transplant patients. It has high intrapatient variability (Tac-IPV), which has been reported to affect graft function by predisposing patients to rejection or nephrotoxicity. We conducted this study with the aim of assessing the influence of Tac-IPV on 2-year graft function, biopsy-proven rejection, and infections in compliant renal recipients. In this single-center retrospective analytic cross-sectional study, 250 patients who underwent transplantation from March 21, 2018, to March 20, 2020 and had at least three outpatient tacrolimus trough levels on the same daily dose 6 to 12 months after transplantation were recruited. Tac-IPV was defined as a coefficient variation of > 15%. Graft function, biopsy-proven rejection, cytomegalovirus (CMV) and BK virus viremia, and calcineurin inhibitor (CNI) toxicity were evaluated. Of 202 transplant recipients, 128 were included with a mean age of 45.48 ± 13.14 years. The median Tac-IPV was 13.28% with 43.75% of patients with Tac-IPV > 15%. There were no significant differences in graft function, rejection, CNI toxicity, and CMV viremia among the groups during the 24-month study (P > .05). However, BK viremia was significantly higher among patients with Tac-IPV > 15% (13 vs. 2.9%, P = .042). The risk of antibody mediated rejection alone (22.7 vs. 2.9%) or any kind of rejection (22.7 vs. 11.8%) was significantly higher in patients with higher Tac-IPV, and in those who had mean trough levels below 7 ng/mL (P = .015, .032; respectively). Tac-IPV is low in adherent patients (with the median of 13.28%) and maintaining tacrolimus trough level above 7 ng/mL can overcome the adverse graft outcome of Tac-IPV in compliant kidney transplant recipients. DOI: 10.52547/ijkd.7815.

BK Viremia and Viruria Does Not Depend on the Type of Double-J Stent Used During Kidney Transplantation.

BK virus is a major cause of chronic renal allograft failure.Transplant ureteral stent use has been reported as a risk factorfor BK virus infection. Recently, the use of a new type of ureteral stent (Magnetic Black Star) was reported in kidney transplant recipients. The aim ofthis preliminary report was to compare BK virus viremia and viruria occurrence depending on the type of double-J stent (standard versus Magnetic Black Star). We included all kidney transplants performed in our center from January to December 2022. Each case had double-J stent placement. Indwelling stents were either a 6- or 7-Fr standard double-J stent or a 6-Fr Magnetic Black Star double-J stent. The type of double-J stent was chosen according to the surgeon's preference. A standard BK virus screening protocol was followed during the study period, which consisted of routine polymerase chain reaction examination of plasma and urine samples during monthly follow-ups. We assessed 120 patients without missing data: 92 patients received standard double-J stents and 28 patients received Magnetic Black Star stents. Patients were mostly male in the standard group (70.7%) versus the Magnetic Black Star group (42.9%) (P = .01). ABO- and HLA-incompatible transplant rates were similar in both groups. BK viremia occurrence and BK viruria occurrence were similar between groups at 1 month, 3 months, and 6 months. This preliminary study showed no differences concerning BKvirus infection depending on the type of double-J stents used during kidney transplant.

Differential effects of desensitization therapy on BK virus viremia after living donor kidney transplantation

Differential effects of desensitization therapy on BK virus viremia after living donor kidney transplantation

BK Viremia and Changes in Estimated Glomerular Filtration Rate in Children and Young Adults after Hematopoietic Cell Transplantation

Kidney disease in allogeneic hematopoietic cell transplantation (HCT) recipients is associated with increased mortality rates. BK virus (BKV) viremia has been associated with kidney dysfunction in pediatric HCT recipients; however, few studies have investigated longer-term kidney outcomes in association with BKV in this population. Here we assessed the relationship between BK viremia and changes in estimated glomerular filtration rate (eGFR) in children in the first year post-HCT. We selected 136 patients age ≤26 years who underwent HCT in 2007 to 2018 at a single center and had plasma BK viral load data available at 2 time points, weeks 4 to 7 post-HCT and weeks 10 to 13 post-HCT from prospectively collected stored plasma samples. A total of 272 samples were analyzed for BKV using quantitative PCR. We used multivariate linear models to determine the association of BK viremia and change in eGFR by 1 year post-HCT. Forty percent of the patients (54 of 136) had BKV detection in weeks 4 to 7, 13% of whom (7 of 54) had a BK viral load of ≥10,000 copies/mL, and 46% (62 of 136) had BKV detected in weeks 10 to 13, 34% (21 of 62) of whom had a BK viral load of ≥10,000 copies/mL. The mean decline in eGFR was 25.73 mL/min/1.73 m2 by 1 year post-HCT. In multivariate models, a BK viral load of ≥10,000 copies/mL during weeks 4 to 7 was associated with a mean decline in eGFR of 30.6 mL/min/1.73 m2 (95% confidence interval, -55.94 to -5.17; P=.019) compared with a BK viral load <10,000 copies/mL. In adjusted analyses, a high BK viral load in the blood (≥10,000 copies/mL) was associated with a significant decline in eGFR by 1 year post-HCT.

Proteomic analysis of urinary extracellular vesicles of kidney transplant recipients with BKV viruria and viremia: A pilot study.

To better define the biological machinery associated with BK virus (BKV) infection, in kidney transplantation, we performed a proteomics analysis of urinary extracellular vesicles (EVs). Twenty-nine adult kidney transplant recipients (KTRs) with normal allograft function affected by BKV infection (15 with only viremia, 14 with viruria and viremia) and 15 controls (CTR, KTRs without BKV infection) were enrolled and randomly divided in a training cohort (12 BKV and 6 CTR) used for the mass spectrometry analysis of the EVs (microvesicles and exosomes) protein content and a testing cohort (17 BKV and 9 CTR) used for the biological validation of the proteomic results by ELISA. Bioinformatics and functional analysis revealed that several biological processes were enriched in BKV (including immunity, complement activation, renal fibrosis) and were able to discriminate BKV vs. CTR. Kinase was the only gene ontology annotation term including proteins less abundant in BKV (with SLK being the most significantly down-regulated protein). Non-linear support vector machine (SVM) learning and partial least squares discriminant analysis (PLS-DA) identified 36 proteins (including DNASE2, F12, AGT, CTSH, C4A, C7, FABP4, and BPNT1) able to discriminate the two study groups. The proteomic profile of KTRs with BKV viruria alone vs. viremia and viruria was quite similar. Enzyme-linked immunosorbent assay (ELISA) for SLK, BPNT1 and DNASE2, performed on testing cohort, validated proteomics results. Our pilot study demonstrated, for the first time, that BKV infection, also in the viruric state, can have a negative impact on the allograft and it suggested that, whether possible, an early preventive therapeutic strategy should be undertaken also in KTRs with viruria only. Our results, then, revealed new mechanistic insights into BKV infection and they selected potential biomarkers that should be tested in future studies with larger patients' cohorts.

Seroprevalence and newly isolated strains of LT-Ag gene (MMGHA2 and MM GHA5) of BK Polyomavirus in A Sample of Iraqi renal transplant recipients

Background: BK virus (BKV) opportunistic viral infection causes nephropathy and allograft loss in renal transplant recipients (RTRs).Aims: Investigating BKV seropositivity, viremia rate and renal function were the primary goals of this study, in addition to the molecular study of the Iraqi BKV strains (LT antigen gene).Settings and Design: Case-control study.material and methods: Serum and plasma specimens were collected from 106 RTR and 100 non-RTR. Serum samples were analyzed for anti-BK IgG antibodies by BK-IgG ELISA kit. Plasma samples were used for detection of large tumor (LT-Ag) gene region of BKV by RT-PCR technique and then sequenced by Sanger's method.Statistical analysis: frequencies, percentages, and Chi square-test by SPSS v.28Results: The Study showed that 114 (55.3%) have a positive result for BK-IgG, so there was no significant difference between seropositivity of BKV IgG antibody among the studied groups, p =0.191. On the other hand, a total of 206 subjects, 31 (15.0%) had positive viremia and 175 (85.0%) were negative. Renal function showed highly significant differences (p ≤0.000) between seropositive and negative RTR patients. 2 sequences of Iraqi local strains were deposited in the GenBank with the accession numbers LC718551.1 and LC718552.1Conclusions: The viremic state of BKV in RTR has similarly no impact on renal function. While the highly significant association between seropositivity of BK-IgG with high levels of serum creatinine. New strains of BKV were found in the Iraqi RTR patients with 98% similarity with the reference gene.

CT-321 Uncommon Viral Infections in Patients Treated With CAR-T Cell Therapy: Concurrent Adenovirus and BK Virus Infection in a Mantle Cell Lymphoma Patient Within 30 Days After Receiving Brexucabtagene Autoleucel

Chimeric antigen receptor-T (CAR-T) cell therapy has emerged as an immunotherapy option for several hematological malignancies. Patients treated with CAR-T cell therapy are immunocompromised and prone to infections. However, limited data exist regarding prophylaxis and management strategies, which vary among institutions. We report a single-institution experience of adenovirus (AdV) infection treatment following CAR-T cell therapy. Case report. Academic referral center. A 67-year-old man with high-risk mantle cell lymphoma previously treated with chemoimmunotherapy and ibrutinib received brexucabtagene autoleucel for refractory disease. Treatment was complicated by grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS), warranting corticosteroid treatment that was tapered over 4 weeks, and cytokine release syndrome (CRS), resolved with tocilizumab. The patient was admitted within 30 days post-CAR-T cell therapy with pancytopenia and bilateral pulmonary infiltrates. His only symptoms were fatigue and malaise. A respiratory viral panel was positive for AdV. Further infectious testing revealed AdV viremia at 128,000 copies/mL and viruria at 7.10E+07 copies/mL, as well as BK viremia at 5,200 copies/mL and viruria >62,800,000 copies/mL. The patient was initially treated with intravenous immune globulin and then started on intravenous cidofovir 1 mg/kg with pre- and post-hydration. Adenovirus and BK virus levels were monitored in blood and urine weekly. Cidofovir was continued until the plasma level of AdV was <400 copies/mL on two separate occasions. AdV viremia and viruria, BK virus viremia and viruria, symptoms. Viral levels of AdV steadily decreased over 3 weeks to <190 copies/mL in plasma and 5200 copies/mL in urine. No new symptoms other than intermittent hematuria were noted. BK virus plasma levels increased temporarily, but fluoroquinolones were not given due to allergy and scarce evidence of their efficacy. Immunosuppression in patients receiving CAR-T cell therapy is multifactorial. CRS and ICANS are common acute toxicities that frequently require treatment with immunosuppressive agents. Prolonged use of corticosteroids has been identified as a predictor of infection after CAR-T cell therapy. Clinical trials addressing appropriate infection prophylaxis and treatment in this population are needed.

Correlation between CYP3A5 gene polymorphism and BK virus infection in kidney transplant recipients

BackgroundCytochrome P450 3A5 (CYP3A5) includes two active genotypes, namely CYP3A5*1/*1 or *1/*3 with the fast metabolic activity and CYP3A5*3/*3 with slow metabolic. We retrospectively analyzed the correlation between CYP3A5 gene polymorphism and the susceptibility to the BK virus (BKV) infection in renal transplant recipients. MethodsAccording to the inclusion/ exclusion criteria, we selected 134 recipients who received kidney transplantation at the Renmin Hospital of Wuhan University from January 2019 to December 2019. Based on the pre-operative CYP3A5 sequencing results, 134 recipients were divided into two groups: those expressing the fast metabolic CYP3A5*1/*1 or *1/*3 genotype; and, those expressing slow metabolic CYP3A5*3/*3 genotype. These two recipient groups were then analyzed for the BKV infection rate with different metabolic types to establish the potential relationship between CYP3A5 gene polymorphism and BKV infection. ResultsThe overall incidence of BKV viruria was 37.3%, whereas BKV viremia was 4.5% among all 134 recipients. The fast metabolism group had 9.1% incidence of BKV viremia and 49.1% incidence of BKV viruria. In contrast, the slow metabolism group had only 1.3%incidence of BKV viremia (P = 0.031) with only 29.1% BKV viruria (P = 0.011). The incidence of low levels of urinary BKV in the fast metabolism group was higher than that in the slow metabolism group (P = 0.005), while no significant statistical difference in the incidence of high levels of urinary BKV and high and low levels of blood BKV. ConclusionAfter kidney transplantation, CYP3A5 gene polymorphism of recipients present a certain relationship with the occurrence of BKV infection, which may be of value for the prediction and prevention of BKV infection.

Effects of tacrolimus intrapatient variability and CYP3A5 polymorphism on the outcomes of pediatric kidney transplantation.

The intrapatient variability (IPV) of tacrolimus (Tac) is associated with the long-term outcome of kidney transplantation. The CYP3A single-nucleotide polymorphism (SNP) may affect the IPV of Tac. We investigated the impact of IPV and genetic polymorphism in pediatric patients who received kidney transplantation. A total of 202 pediatric renal transplant recipients from 2000 to 2016 were analyzed retrospectively. The IPV was calculated between 6 and 12months after surgery. Among these patients, CYP3A5 polymorphism was analyzed in 67 patients. The group with high IPV had a significantly higher rate of de novo donor-specific human leukocyte antigen antibodies (dnDSA) development (35.7% vs. 16.7%, p=.003). The high IPV group also had a higher incidence of T-cell-mediated rejection (TCMR; p<.001). The high IPV had no significant influence on Epstein-Barr virus, cytomegalovirus, and BK virus viremia but was associated with the incidence of posttransplant lymphoproliferative disorders (p=.003). Overall, the graft survival rate was inferior in the high IPV group (p<.001). The CYP3A5 SNPs did not significantly affect the IPV of Tac. In the CYP3A5 expressor group, however, the IPV was significantly associated with the TCMR-free survival rate (p<.001). The IPV of Tac had a significant impact on dnDSA development, occurrence of acute TCMR, and graft failure in pediatric patients who received renal transplantation. CYP3A5 expressors with high IPV of Tac showed worse outcomes, while the CYP3A5 polymorphism had no impact on IPV of Tac.

Significance of caveolin-1 immunohistochemical staining differences in biopsy samples from kidney recipients with BK virus viremia.

BK virus infections which usually remains asymptomatic in healthy adults may have different clinical manifestations in immunocompromised patient population. BK virus reactivation can cause BK virus nephropathy in 8% of kidney transplant patients and graft loss may be seen if not treated. Clathrin or Caveolar system is known to be required for the transport of many viruses from Polyomaviruses family including BK viruses. In this study, kidney transplant patients with BK virus viremia were divided into two groups according to the BK virus nephropathy found in kidney biopsy (Group I: Viremia+, Nephropathy+ / Group II: Viremia+, Nephropathy-). Kidney biopsies were examined with immunohistochemical staining to determine the distribution and density of the Caveolin-1 and Clathrin molecules. Immunohistochemical staining of the 31 pathologic specimens with anti-caveolin-1 immunoglobulin revealed statistically significant difference between group-I and group-II. The number of the specimens stained with anti-caveolin-1 was less in group I. On the other hand, we did not find any difference between the groups regarding the anti-clathrin immunochemical analysis. According to these findings, caveolin-1 expression differences in kidney transplant patients may be important in disease progression.

Causes of Renal Allograft Injury in Recipients With Normal Donor-derived Cell-free DNA

Background.Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for the early detection of organ transplant rejection and other causes of graft injury. For nonrejection renal injuries, there is little information about the performance characteristics of this biomarker. We highlight some of the possible causes of kidney injury that may arise in patients with normal dd-cfDNA levels.Methods.We performed a retrospective analysis of solitary renal transplant cases between January 2017 and November 2019. Those who had an abnormal laboratory or pathological finding within 1 mo of a normal dd-cfDNA test were selected. Subgroups were stratified for those who had normal or abnormal/rising serum creatinine, and differences between the groups were analyzed.Results.Of 414 individuals who received a kidney transplant, 24 (7.5%) had a total of 41 normal dd-cfDNA values and 51 abnormal laboratory tests or histologic findings. The most common graft-injuring event was BK virus viremia (24 of 51). Other abnormal findings included urinary traction infections (n = 4), CMV viremia (n = 4), and biopsies demonstrating antibody-mediated rejection (AMR) (n = 2), T cell–mediated rejection (n = 1), focal segmental glomerulosclerosis (n = 2), nondonor-specific antibody chronic AMR (n = 1), and interstitial fibrosis and tubular atrophy (n = 7). Subgroup analysis of those with normal dd-cfDNA and normal/stable versus abnormal/rising creatinine showed that BK virus viremia was the most common abnormal finding in both groups at 53% and 38% respectively. On biopsy, 1 case of acute T cell–mediated rejection (1B and 2B) was seen with normal/stable creatinine, whereas 1 of nonspecific C4d focally positive and 1 of nondonor-specific antibody AMR were seen with abnormal/rising creatinine.Conclusions.Low levels of serum dd-cfDNA do not preclude detection of active graft-injuring events and that subclinical injuries may be developing. Context is important in the interpretation of dd-cfDNA, so renal biopsy remains a part of the diagnostic pathway for allograft dysfunction and maintenance of allograft health.

Effect of post-perfusion hyperoxemia on early graft function in renal transplant recipients: a retrospective observational cohort study.

The effects of hyperoxemia on the transplanted grafts arouse interest nowadays, particularly intraoperative hyperoxemia, on transplant kidney function and survival in the 1-year post-operative period. We aimed to investigate the effect of post-perfusion (5 min after perfusion) hyperoxemia on early graft function and survival in renal transplant recipients. Two hundred forty-seven living donor kidney transplant recipients were included in the study. Patients were divided into the three groups according to their partial arterial oxygen pressure in post-perfusion blood gas samples: group 1: normoxia (n = 52, PaO2 pressure: < 120 mmHg, 103 ± 13); group 2: moderate hyperoxemia (n = 121, PaO2: 120-200 mmHg, 169 ± 21); group 3: severe hyperoxemia (n = 74, PaO2: > 200 mmHg, 233 ± 25). Graft functions (serum creatinine levels, estimated-glomerular filtration rate values, spot urine protein/creatinine ratio), survival rates, and groups' clinical outcomes were compared in the first year after transplantation. Graft survival rates were similar in the groups and the rate of BK virus viremia was the lowest in the group 3 (groups 1, 2, and 3: 15.4% (n = 8), 6.6% (n = 8), 1.4% (n = 1), respectively, P: 0.009). Serum creatinine and proteinuria levels were lower, and estimated-glomerular filtration rate values were higher in group 3. A negative correlation between partial arterial oxygen pressure and serum creatinine levels and a positive correlation with estimated-glomerular filtration rate value were noted. These results were confirmed by univariate and multivariate analyses. We demonstrated that the kidney transplant recipients with post-perfusion hyperoxemia have better early graft functions and lower BK virus viremia rates. ClinicalTrials.gov Identifier: NCT04420897.

Management of BK virus-associated haemorrhagic cystitis in allogeneic stem cell transplant recipients.

BK virus (BKV)-related haemorrhagic cystitis (HC) is an important cause of morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). The various risk factors include high-level BKV viruria and/or viremia, myeloablative conditioning, acute graft versus host disease (GVHD), cytomegalovirus viremia, and unrelated or HLA-mismatched donor. The presence of high plasma BK viral load and cytopenias have been implicated as important predictors for protracted disease course. These patients frequently require hospitalisation which may extend for several weeks. Supportive measures in the form of analgesics, intravenous hydration, bladder irrigation, and transfusion support remain the mainstay of management. Various drugs have been used with limited success in this setting. These include antiviral drugs, fluoroquinolones, leflunomide, growth factors, clotting factors, estrogens, and prostaglandins. The role of adoptive cellular immunotherapy has also been explored but lacks clinical validation. The strategies aimed at expediting urothelial repair like hyperbaric oxygen therapy (HBOT), intravesical fibrin glue and platelet-rich plasma (PRP) are emerging. Some patients with severe disease do require surgical intervention to relieve urinary obstruction. The frequent co-occurrence of acute GVHD and CMV disease further complicates the management in such patients. There is an unmet need for effective and evidence-based options for the prevention and management of this disease. Due to lack of robust data supported by randomised trials, the acceptability of the available guidelines to simplify the treatment is expected to be low. Despite the availability of various treatment options, the management of BKV-related HC in day-to-day practice continues to be a challenge. The aim of this article is to put forward an up-to-date review of the preventive and therapeutic strategies for BKV-related HC.

BK Virus Infections in Pediatric Patients with Hematopoietic Stem Cell Transplantation

Aim: BK virus (BKV)-associated hemorrhagic cystitis (HC) is a common complication in patients after hematopoietic stem cell transplantation (HSCT). The aim of this study was to investigate the incidence of BKV infection in pediatric patients receiving HSCT.&#x0D; Material and Methods: Total of 51 patients aged between 16 months and 16 years old and followed up between October 2015 and September 2017 were included in the study. The patients were monitored by quantitative real-time polymerase chain reaction (Anatolia Geneworks, Turkey) test for the detection of BKV DNA in urine and blood.&#x0D; Results: Of patients, 46 received allogeneic HSCT and 5 autologous HSCT. BKV DNA positivity was detected in urine and/or blood of total 27 (52.9%) patients in whom 26 (56.5%) of 46 patients with allogeneic transplantation, and 1 (20.0%) of 5 patients with autologous transplantation. BKV viral load in urine &gt;107 copies/ml required for preemptive treatment was detected in 12 (26.1%) of 46 patients received allogeneic HSCT. The development of HC was prevented in 9 (75.0%) of the 12 patients given preemptive treatment, while 3 (25.0%) cases developed HC and cured by treatment. BKV viruria was detected &gt;109 copies/ml in two weeks before the onset of HC and was accepted as a prognostic indicator for predictive diagnosis of HC. BKV viremia was found &gt;104 copies/ml in 1 patient within two weeks before the onset of cystitis.&#x0D; Conclusion: Screening for BKV infection, especially BKV viruria in HSCT patients, is recommended for the predictive diagnosis of HC in patients at high risk.

Analysis of risk factors influencing the BK polyomavirus replication in patients with ESRD waiting for kidney transplantation

BackgroundSince the pre-transplant status affects the renal transplantation success and ultimately the survival rate, identifying the probable risk factors that increase the chance of BK virus replication in end-stage renal disease patients can be included in proposing proper surveillance guidelines during pre and post-transplantation. MethodsA descriptive cross-sectional study was performed by collecting plasma samples from 192 ESRD patients undergoing hemodialysis for at least 3 months. Quantitative Real-time PCR assay was used to detect and measure the BK viral load. Demographic and clinical characteristics of the patients who had BK viremia were documented. Results14 (7.3%) out of our 192 participants had BK virus viremia (95%CI 4.2%–11.6%). Demographic characteristics including etiology of ESRD and underlying diseases, mean duration and frequency of dialysis, co-infection with HBV and HCV did not affect the virus replication, since the difference between patients with BK virus viremia and BK virus negative individuals was not statistically significant. However, the statistical significance of the mean age of men with BKV and without BK virus viremia was found (OR: 3.42, P = 0.02 95%CI 0.86–13.61). Also, multiple regression analyses of some other parameters revealed that old age, high body mass index and male gender can be predictive factors of BK virus viremia in ESRD patients. ConclusionBased on our findings, elderly male had higher chance of being exposed to BK virus viremia. Some other demographic characteristics such as a high BMI, old age and gender (male) can increase the risk of BK viremia in patients with ESRD prior to kidney transplantation.

Intravenous immunoglobulin as a preventive strategy against BK virus viremia and BKV-associated nephropathy in kidney transplant recipients-Results from a proof-of-concept study.

BK virus (BKV) replication occurs frequently in kidney transplant recipients (KTR), potentially leading to BKV-associated nephropathy (BKVAN) and graft loss. Patients with high titers of BKV-neutralizing antibodies (NAbs) are protected against BKV replication, and intravenous immunoglobulin (IVIg) infusion can increase NAb titers. We investigated whether early IVIg administration prevents BKV replication in patients with low NAb titers (<4 log10 against the BKV-specific genotype). Based on NAb titers on the day of transplantation, KTR followed in the Strasbourg University Hospital (n=174) were retrospectively divided into the following 3 risk categories for BKV replication: (1) patients with low NAb titers ("high-risk") who received IVIg for the first 3 posttransplant months (n=44), (2) patients with low NAb titers ("high-risk") who did not undergo IVIg treatment (n=41), and (3) patients with high NAb titers ("low-risk") who did not receive IVIg (n=89). At 12 posttransplant months, the incidence of BKV viremia in the high-risk group treated with IVIg (6.8%) was similar to that observed in the low-risk group (10.1%) and markedly lower than that of the untreated high-risk group (36.6%; P<.001). Similar results were observed with regard to BKVAN. We conclude that IVIg may be a valuable strategy for preventing BKV replication.

Development and validation of an optimized integrative model using urinary chemokines for noninvasive diagnosis of acute allograft rejection.

The urinary chemokines CXCL9 and CXCL10 are promising noninvasive diagnostic markers of acute rejection (AR) in kidney recipients, but their levels might be confounded by urinary tract infection (UTI) and BK virus (BKV) reactivation. Multiparametric model development and validation addressed these confounding factors in a training set of 391 samples, optimizing the diagnostic performance of urinary chemokines. CXCL9/creatinine increased in UTI and BKV viremia with or without nephropathy (BKVN) (no UTI/leukocyturia/UTI: -0.10/1.61/2.09, P=.0001 and no BKV/viremia/BKVN: -0.10/1.90/2.29, P<.001) as well as CXCL10/creatinine (1.17/2.09/1.98, P<.0001 and 1.13/2.21/2.51, P<.001, respectively). An optimized 8-parameter model (recipient age, sex, estimated glomerular filtration rate, donor specific antibodies, UTI, BKV blood viral load, CXCL9, and CXCL10) diagnosed AR with high accuracy (area under the curve [AUC]: 0.85, 95% confidence interval [CI]: 0.80-0.89) and remained highly accurate at the time of screening (AUC: 0.81, 95% CI: 0.48-1) or indication biopsies (AUC: 0.85, 95% CI: 0.81-0.90) and within the first year (AUC: 0.86, 95% CI: 0.80-0.91) or later (AUC: 0.90, 95% CI: 0.84-0.96), achieving AR diagnosis with an AUC of 0.85 and 0.92 (P<.0001) in 2 external validation cohorts. Decision curve analyses demonstrated the clinical utility of the model. Considering confounding factors rather than excluding them, we optimized a noninvasive multiparametric diagnostic model for AR of kidney allografts with unprecedented accuracy.

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.

P1759NEPHROTOXICITY OF CALCINEURIN INHIBITORS AS A RISK FACTOR FOR BK VIRUS REPLICATION AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims BK virus nephropathy (BKVN) represents a serious complication of kidney transplantation and is responsible for significant percentage of transplanted kidneys prematurely terminating their function. Its occurrence is considered a complication of immunosuppressive therapy and is closely related to its intensity. The aim of our prospective study was to evaluate the incidence of subclinical and clinically manifest nephrotoxicity of calcineurin inhibitors (CI) in repeated protocol kidney graft biopsies as a manifestation of excessive immunosuppression and to evaluate its relationship to the PCR confirmed active BKV replication and bioptically proven BKVN during the first year after transplantation. Method In a group of 161 newly transplanted patients we prospectively evaluated 457 consecutive protocol renal biopsies performed within the first year after transplantation. Using the CI nephrotoxicity score, the incidence of nephrotoxicity was monitored. Findings were correlated with laboratory (PCR) and histological evidence of active BK virus (BKV) replication and BKVN. Results When compared to the normal histology, nephrotoxicity was associated with more frequent significant BKV viraemia and viruria (P = 0.02 and P = 0.01, respectively) and more common occurrence of BKVN. The persistence of toxicity in the subsequent biopsy proved to be a negative risk factor of significant BKV viraemia and viruria (P = 0.03 and P = 0.01, respectively), independently of the initial BKV status of the monitored groups. Toxicity could also be used as a predictor of significant viraemia and viruria (P = 0.02 and P = 0.01, respectively) even in the absence of viral replication at the time of initial biopsy. Conclusion Early histological detection of CI nephrotoxicity followed by pre-emptive CI dose reduction might prevent significant BKV reactivation in the risky first posttransplant year. The evaluation whether a regression of histological signs of nephrotoxicity after a CI dose reduction leads to a reduction in BKV replication, and whether a more frequent occurrence of rejection does not complicate further posttransplant course, will be the subject of our further investigation. Supported by grant of Ministry of Health, Czech Republic DRO (FNOL 00098892) – 87-68.