BK Virus Nephropathy Research Articles

Risk factors for BK virus infection in DCD donor kidney transplant recipients.

BK virus infection after kidney transplantation can negatively impact the prognosis of patients. However, current risk factor analyses primarily focus on BK virus nephropathy, while BK viruria and BK viruria progressing to BK viremia receive less attention. This study aims to analyze the risk factors associated with BK viruria and BK viruria progressing to BK viremia in recipients of donation after cardiac death (DCD), with the goal of facilitating early intervention. Donor characteristics and clinical data of recipients before and after transplantation were evaluated, and logistic univariate and multivariate analyses were performed to determine the risk factors associated with BK viruria and the progression of BK viruria to BK viremia. Additionally, machine learning techniques were employed to identify the top five features associated with BK viruria evolving into BK viremia. During a median follow-up time of 1,072 days (range 739-1,418), 69 transplant recipients (15.6% incidence rate) developed BK viruria after transplantation, with 49.3% of cases occurring within 6 months post-transplantation. Moreover, 19 patients progressed to BK viremia. Donor age [OR: 1.022 (1.000, 1.045), p = 0.047] and donor procalcitonin (PCT) levels [0.5-10 ng/ml; OR: 0.482 (0.280, 0.828), p = 0.008] were identified as independent risk factors for BK viruria. High BK viruria [OR: 11.641 (1.745, 77.678), p = 0.011], recipient age [OR: 1.106 (1.017, 1.202), p = 0.018], and immunoinduction regimen [ATG; OR: 0.063 (0.006, 0.683), p = 0.023] were independent risk factors for BK viruria progressing to BK viremia. Machine learning analysis confirmed the importance of high BK viruria, recipient age, and immunoinduction regimen (ATG) in predicting the progression of BK viruria to BK viremia. The development and progression of BK virus in DCD kidney transplant recipients is influenced by multiple factors. Early intervention and treatment could potentially extend the lifespan of the transplanted organ.

#4251 KIDNEY TRANSPLANTATION WITH DONOR-SPECIFIC ANTIBODIES: A GROWING NEED

Abstract Background and Aims Preformed donor specific antibodies in kidney transplant (KT) recipients are associated with higher risk of antibody mediated rejection (ABMR) and poorer graft survival. However, remaining a long time on the waiting list is strongly related to worse patient outcomes. We aimed to analyze KT recipients with preformed DSA with mean intensity fluorescence (MFI) who received induction therapy adapted to their higher immunological risk. Method We conducted a cohort retrospective study. All KT with preformed DSA performed in our center since May 2010 until March 2021 were included in the analysis. The presence of DSA was evaluated through Luminex Single Antigen (SA®) technology. All KT were performed with cadaveric kidney donor and with previous negative test by CDC crossmatch. The induction therapy in the presence of DSA included steroids, thymoglobulin, rituximab, plasmapheresis and standard treatment with tacrolimus and mycophenolate. Results During the study period 27 KT with preformed DSA were carried out. Recipient median age was 49 (IQR 40-62) years and 70,2% were women. Dialysis vintage was 5.8 (IQR 2.3-10.2) years. 63% were blood group A and 29,5% blood group 0. 29.6% were also included in the Hypersensitized National Programme (PATHI). The main causes of sensitization were previous KT (55.6%), pregnancy (29.6%) and blood transfusions (3.7%). 63% received KT with preformed DSA class I (median MFI 2218) and 37% with preformed DSA class II (median MFI 1900). Median calculated PRA was 90.5% (IQR 80.6-98.3). Median follow up time was 32.5 (IQR 12.3-61.2) months. Seventeen kidney biopsies were carried out. The most frequent findings were acute tubular necrosis (35.3%) and active ABMR (23.5%). DSA disappeared in most of the cases in successive analysis (81%) without any differences between both DSA classes. Median serum creatinine was 1.25 (IQR 0.97-1.75) mg/dl at 12 months and 1.65 (IQR 1.1-1.81) mg/dl at 24 months. In the post-transplantation period 2 patients were diagnosed with malignant solid organ tumors, 3 developed BK nephropathy, 5 CMV asymptomatic reinfection, and 9 recurrent urinary tract infections. During the observation time, 8 grafts were lost (29.6%): 3 due to patient deaths with functioning grafts and 5 due to graft failure (3 chronic ABMR, 1 active ABMR and 1 BKV nephropathy). Graft survival was 98% and 12 months and 92% at 24 months, respectively. Conclusion DSA with MFI low levels must be considered as a risk factor of ABMR and not as a contraindication to perform KT. A reinforced induction immunosuppression therapy enables KT to patients with high immunological risk and avoid prolonged time on the waiting list.

#6310 ANALYSIS OF THERAPEUTIC ATTITUDES TOWARDS BK VIRUS INFECTION IN RENAL TRANSPLANTATION: A RETROSPECTIVE COHORT STUDY

Abstract Background and Aims BK virus infection continues to be one of the most common clinical issues encountered by transplants providers, which can lead to BK virus nephropathy and, ultimately, graft loss. Despite its importance, there are still many uncertainties surrounding effective prevention and treatment strategies. The aim of this study is to evaluate the BK virus prevalence disease in a cohort of kidney transplant patients, examine consequences of immunosuppression regimens readjustments and assess the progression of viremia and viruria. Method This study analyzed a cohort of patients who received kidney transplants from January 2011 to January 2020 and had a minimum graft survival of three months. In accordance with our established protocol, viremia was measured on a quarterly basis during the first year after transplantation and annually thereafter. BK virus infection (BKVi) was defined as a plasma viral load, determined by real-time PCR, of 10,000 copies/ml or greater, or a viral load of 5,000 copies/ml or greater if accompanied by viruria of greater than 10 million copies/ml. Out of the 490 patients initially selected, 42 were excluded from the study due to inadequate data. Results The maximum levels of viremia during the course of the study were classified as follows: viremia ≥ 10,000 (N = 78; 17.4%), between 5,000-10,000 (N = 11; 2.4%), between 500-1,000 (N = 17; 3.8%) and undetectable (N = 342; 76.3%). The maximum levels of viruria were classified as: viruria ≥ 1 million (N = 98, 21.9%), between 999,999-100,000 (N = 15; 3.3%), between 99,999-10,000 (N = 20, 4.5%) and undetectable (N = 315; 70.3%). In the group diagnosed with BKVi, viremia ≥ 10,000 appeared at a median post-transplant time of 5.8 (2.9-11.7) months. The treatment approach involved replacing tacrolimus or mycophenolate with mTOR inhibitor, based on the patient's immunological risk. In some cases of high immunological risk or intolerance to mTOR inhibitor during the first month, treatment with tacrolimus and mycophenolate was continued. If the previous regimens were not effective, treatment with cyclosporine and mTOR inhibitor was initiated in some cases. The key results are summarized in the Table 1. Conclusion The combination of tacrolimus and mTOR inhibitor appears to be an effective option for BK virus infection, while the combination of mTOR inhibitor and mycophenolate has a high discontinuation rate, which can result in subsequent increase in viremia. In cases where there is no favorable response, the combination of cyclosporine and mTOR inhibitor can be effective. The changes in immunosuppression in patients with BKVi did not result in significant differences in renal function at one year or five years after transplantation, although the sample size is limited and more research is needed to confirm this. Keeping tacrolimus and mycophenolate may lead to a longer time until viremia becomes negative, which could have long-term implications for renal function.

#6147 BELATACEPT OUTCOMES IN PEDIATRIC KIDNEY TRANSPLANTATION: AN INTERNATIONAL MULTICENTER STUDY

Abstract Background and Aims Belatacept is a co-stimulation blocker associated with better long-term outcomes in adult patients compared to CNI based regimens. Data on its use in older children and young adults are lacking. We are the 1st to report outcomes for 45 pediatric kidney transplant recipients converted to belatacept. Method 45 patients were included from 4 centers (USA and France) between 05/2018 and 12/2021. Patients received an induction with basiliximab (n = 39) or ATG (n = 6). Maintenance immunosuppression included CNI, MMF +/− steroids. Patients’ viral status (EBV, CMV) were monitored monthly and allograft biopsies were performed prior and ∼6 months after starting belatacept. The first 5 belatacept injections were administered at 5 mg/kg/dose (10 mg/kg/dose if early conversion) every 2 weeks, then monthly. CNI were progressively reduced and stopped. MMF doses were also increased at CNI withdrawal. Results Median age at conversion was 17.7 y (range 10.3-20.6). 7/45 patients received an early conversion (median: 1 month post-transplant, IQR 0.5-1.2): 6 patients because of delayed graft function and 1 to avoid CNI toxicity (post-transplant diabetes). 38/45 patients were converted after a median of 4.1 years post-transplant (IQR 1.7-6.0). Conversion indication was based on the need for long term CNI avoidance: either because of toxicity (histology, post-transplant diabetes, tremors; n = 13) or sub-optimal creatinine (n = 12) or to improve adherence (e.g. monthly IV-treatment, n = 13). CNI were withdrawn in 42/45 patients by a median of 2.4 months (IQR 1.4-6.0). GFR was stable or improved over a median follow-up time of 1.6 years (IQR 1.1-2.4), Fig 1 A. Rejection episodes were observed in 10/45 patients (22%) after a median of 10.2 months (IQR 6.1-15.8) and included 7 TCMR, 2 ABMR and 1 mixed rejection. None of these patients were converted early (<3 m), 5 had been converted for non-adherence, 4 had pre-existing DSA and 4 had prior history of rejection. Evolution of GFR in rejectors is shown in Fig 1 B. CNI were reintroduced for 6/10 and belatacept stopped for 3/10. Regarding viral complications, 1 severe BKv nephropathy required the discontinuation of belatacept. All patients were EBV+ at conversion (4 were EBV- at the time of transplant). No EBV replication was observed. Conclusion Selected pediatric kidney recipients benefit from long-term CNI toxicity avoidance, but selection criteria need to be refined to avoid rejection under costimulation blockade.

Kidney Biopsy Findings Among Allogenic Hematopoietic Stem Cell Transplant Recipients With Kidney Injury: A Case Series

The incidence of kidney disease is high in patients after allogeneic hematopoietic cell transplantation (aHCT). Although rarely performed, kidney biopsy may be useful to make a precise diagnosis because several mechanisms and risk factors can be involved, and to adjust the treatment accordingly. This case series aimed to report the spectrum of biopsy findings from patients with kidney injury after aHCT. Single-center retrospective case series. All individuals who underwent a native kidney biopsy, among all adult patients who received aHCT in a tertiary hospital in Montreal (Canada) from January 1, 2010, to December 31, 2020, were identified, and the clinical data were extracted from their medical records. A total of 17 patients were included. Indications for biopsy included acute kidney injury (n=6), chronic kidney disease (n=5), nephrotic syndrome (n=4), and subnephrotic proteinuria (n=2). Pathologic findings from the kidney biopsy were heterogenous: 10 patients showed evidence of thrombotic microangiopathy (TMA), 5 of acute tubular injury, and 4 of membranous nephropathy. Cases of acute interstitial nephritis, BK virus nephropathy, immune complex nephropathy, focal and segmental glomerulosclerosis, minimal change disease, and karyomegalic-like interstitial nephritis were also described. There was no systematic kidney biopsy performed for all patients with kidney injury after aHCT. Only a small proportion of patients with kidney damage underwent biopsy, making the results less generalizable. Kidney biopsy is useful in patients with kidney disease after aHCT to make a precise diagnosis and tailor therapy accordingly. This series is one of the few published studies describing pathologic findings of biopsies performed after aHCT in the context of acute kidney injury and chronic kidney disease. TMA was widely present on biopsy even when there was no clinical suspicion of such a diagnosis, suggesting that the current clinical criteria for a diagnosis of TMA are not sensitive enough for kidney-limited TMA.

319 Optimizing Urinary cell mRNA profiling of kidney allograft recipients: Development of a home processing protocol for noninvasive diagnosis of T cell mediated rejection and BK virus nephropathy

OBJECTIVES/GOALS: Development of a user friendly home kit that enables kidney transplant recipients to process urine at home and post the lysate containing RNA to a Core Laboratory would simplify urinary cell mRNA profiling and facilitate longitudinal monitoring. We report our home processing protocol and investigation of its diagnostic performance characteristics. METHODS/STUDY POPULATION: We developed a home processing protocol (HPP) consisting of urine filtration and lysis of urinary cells, both performed at home by the kidney transplant recipients (KTR) themselves, followed by isolation of total RNA from the lysate and mRNA enrichment using a silica-membrane-based cartridge, both performed at the Core Laboratory. Using the HPP, total RNA was isolated from kidney allograft biopsy-matched urines and absolute copy numbers of CD3εmRNA, CXCL10 mRNA, and 18S rRNA, components of the Clinical Trials in Organ Transplantation 04 (CTOT-04) three-gene TCMR diagnostic signature, and urinary cell BKV VP1 mRNA copy number, were measured using customized RT-qPCR assays. RESULTS/ANTICIPATED RESULTS: CTOT-04 three-gene TCMR diagnostic signature scores in urine processed using HPP discriminated KTR with TCMR (12 TCMR biopsies from 11 KTR) from KTR with no TCMR/BKVN (29 No TCMR/No BKVN biopsies from 29 KTR) (P=0.0005, Mann-Whitney test), and AUROC was 0.84 (95% CI, 0.69 to 0.98). TCMR was diagnosed with sensitivity of 67% (95% CI, 35 to 89) at a specificity of 86% (95% CI, 67 to 95) using the CTOT-04 validated cutpoint of -1.213 (P=0.0016,Fisher exact test). BKV VP1 mRNA copy number in urine processed with HPP discriminated KTR with BKVN (n=7) from KTR with no TCMR/BKVN (n=29) and AUROC was 1.0 (95% CI, 1.00 to 1.00). BKVN was diagnosed with a sensitivity of 86% (95% CI, 42 to 99) at specificity of 100% (95% CI, 85 to 100) with the previously validated cutpoint of 6.5x10^8 BKV VP1 mRNA copies/μg of RNA (P DISCUSSION/SIGNIFICANCE: Urine processed using the HPP predicted TCMR and BKVN in KTR. The HPP represents not only a significant advance towards portability of urinary cell mRNA profiling but also should improve patient management by minimizing visits for urine collection.

Diagnosis of T-cell-mediated kidney rejection by biopsy-based proteomic biomarkers and machine learning.

Biopsy-based diagnosis is essential for maintaining kidney allograft longevity by ensuring prompt treatment for graft complications. Although histologic assessment remains the gold standard, it carries significant limitations such as subjective interpretation, suboptimal reproducibility, and imprecise quantitation of disease burden. It is hoped that molecular diagnostics could enhance the efficiency, accuracy, and reproducibility of traditional histologicmethods. Quantitative label-free mass spectrometry analysis was performed on a set of formalin-fixed, paraffin-embedded (FFPE) biopsies from kidney transplant patients, including five samples each with diagnosis of T-cell-mediated rejection (TCMR), polyomavirus BK nephropathy (BKPyVN), and stable (STA) kidney function control tissue. Using the differential protein expression result as a classifier, three different machine learning algorithms were tested to build a molecular diagnostic model for TCMR. The label-free proteomics method yielded 800-1350 proteins that could be quantified with high confidence per sample by single-shot measurements. Among these candidate proteins, 329 and 467 proteins were defined as differentially expressed proteins (DEPs) for TCMR in comparison with STA and BKPyVN, respectively. Comparing the FFPE quantitative proteomics data set obtained in this study using label-free method with a data set we previously reported using isobaric labeling technology, a classifier pool comprised of features from DEPs commonly quantified in both data sets, was generated for TCMR prediction. Leave-one-out cross-validation result demonstrated that the random forest (RF)-based model achieved the best predictive power. In a follow-up blind test using an independent sample set, the RF-based model yields 80% accuracy for TCMR and 100% for STA. When applying the established RF-based model to two public transcriptome datasets, 78.1%-82.9% sensitivity and 58.7%-64.4% specificity was achieved respectively. This proof-of-principle study demonstrates the clinical feasibility of proteomics profiling for FFPE biopsies using an accurate, efficient, and cost-effective platform integrated of quantitative label-free mass spectrometry analysis with a machine learning-based diagnostic model. It costs less than 10 dollars per test.

Characteristics, risk factors and outcome of BKV nephropathy in kidney transplant recipients: a case–control study

BackgroundFollowing kidney transplantation, BK virus associated nephropathy (BKVN) occurs in 1 to 10% of kidney transplant recipients (KTR) and represents a major cause of graft loss. We aim at identifying factors associated with biopsy proven BKVN among KTR.MethodsWe conducted a retrospective case–control study including all KTR with a biopsy-proven diagnosis of BKVN between 2005 and 2019. Clinical characteristics and outcome were described. For each case, one control KTR without BKV infection was identified and matched by age, transplant date, and donor status. Factors associated with BKVN diagnosis were identified using exact conditional logistic regression. Comparative survival was described using Kaplan–Meier estimator.ResultsSixty-four cases of BKVN were identified among 1737 new kidney transplantation (3.7% prevalence). Clinical characteristics did not differ between groups, except for a higher c-PRA among cases. BKVN occurred in a median time of 11 (5–14.5) months after KT, and was associated with a significantly impaired graft function at diagnosis. Following BKVN, 61 (95%) of the patients had immunosuppression reduction, which led to BKV DNAemia resolution in 49% of cases. In multivariate analysis, factors associated with BKVN diagnosis were lymphopenia < 500/mm3 and a prednisone dose > 7.5 mg/day. Median duration of follow-up was 40 months for both groups. BKVN was associated with a significantly increased risk of graft rejection (P = 0.02) and return to dialysis (P = 0.01).ConclusionsBKVN remains a severe complication in KTR and is associated with an increased risk for acute rejection and return to dialysis. Lymphopenia below 500/mm3 and corticosteroid maintenance therapy are significantly associated with biopsy-proven BKVN diagnosis.

BK DNAemia and native kidney polyomavirus nephropathy following lung transplantation.

BK virus DNAemia (BKPyV) and nephropathy are common after kidney transplant; however, there are limited data on BK infections in nonrenal solid organ transplant recipients. We examined the frequency, clinical and pathologic features, and kidney and lung outcomes of BKPyV and BK virus native kidney nephropathy (BKVN) in lung transplant recipients at our center. Among 878 recipients transplanted from 2003 to 2019, 56 (6%) developed BKPyV at a median of 30.1 months after transplant (range, 0.6-213) and 11 (1.3%) developed BKVN at a median of 46 months after transplant (range, 9-213). The incidence of end-stage kidney disease was significantly higher in patients with peak viral load ≥10 000 copies/mL (39% vs 8%, P < .001). All cases of BKVN were in patients with peak viral load of ≥10 000 copies/mL, and 55% of these patients developed end-stage kidney disease. Despite the reduction of immunosuppression to treat BKVN, only 1 patient developed acute rejection, and lung function was stable >1 year. BKPyV and nephropathy are more common after lung transplantation than previously reported. Routine screening for BKPyV should be considered in all lung transplant recipients.

Prevalence and Impact of BK Polyomavirus in the Ureters of Kidney Donors: Research Letter.

More than 75% of the population is seropositive for BK polyomavirus (BKV), which remains quiescent in the urothelium in immunocompetent hosts. However, it can reactivate in kidney transplant recipients (KTRs), and up to 30% of them will develop BKV viremia in the 2 years following transplant, with a risk of developing BKV-associated nephropathy (BKVAN). Viral reactivation is associated with the level of immunosuppression, but there is currently no way to predict which patients are at high risk for reactivation. As BKV originates from kidney donors, our primary objective was to determine the prevalence of detectable BKV in donor ureters. Our secondary objective was to see if there is a correlation between the presence of BKV in donor urothelium and the development of BKV viremia and BKVAN in KTR. Prospective cohort study. Single-center academic kidney transplant program. Prospective sequential KTRs that received a kidney transplant between March 2016 and March 2017. The presence of BKV in donor ureters was determined by TaqMan-based quantitative polymerase chain reaction (PCR; qPCR). We performed a prospective study which was done on 35 out of the 100 donors initially foreseen to take part in the study. During surgery, the distal part of donor ureter was kept and analyzed by qPCR (to establish the presence of BKV in the urothelium). The primary outcome was the development of BKV viremia in KTR over a period of 2 years after transplant. Secondary outcome was the development of BKVAN. Out of 35 ureters analyzed, only one had a positive qPCR for BKV (2.86%, 95% confidence interval [CI]: [0.07-14.92]). Considering the primary objective would not be met, the study was interrupted after 35 specimens. After surgery, 9 recipients had a slow graft function and 4 had delayed graft function, one of which never recovered graft function. Over the 2-year follow-up, 13 patients developed BKV viremia, while 5 patients developed BKVAN. The patient who received a graft from a positive qPCR donor eventually developed BKV viremia and nephropathy. The specimen analyzed was a distal rather than a proximal portion of the ureter. However, BKV replication is known to concentrate in the corticomedullary junction. BK polyomavirus prevalence in the distal part of donor ureters is lower than previously reported. It cannot be used as a predictor for the development of BKV reactivation and/or nephropathy.

Böbrek nakli hastalarında biyopsi ile kanıtlanmış BK virüs nefropatisi: risk faktörleri, sıklığı ve tedavi yaklaşımı

Purpose: BK virus nephropathy (BKVN) is a latent infection and it is closely associated with immunsuppressive therapy. We aimed in this study to evaluate biopsy-proven BKVN and investigate frequency, risk factors and treatment management. &#x0D; Materials and Methods: In this study, 422 kidney transplant recipients were analysed retrospectively between April 2014 and April 2020 for biopsy-proven BK virus nephropathy. Group I included 16 kidney transplant patients with biopsy-proven BK nephropathy and group II included 36 kidney transplant patients with negative BK virus nephropathy. We aimed demographic, clinical features of kidney transplant recipients with BKVN (group I, n: 16 ) and non-BKVN (group II, n:36) were compared and the factors affecting of BKVN. &#x0D; Results: The mean age of grup I and group II were were 41±14.8 years and 39±15.2 respectively. The patients mean follow-up period of 43±11.2 months. Serum creatinine and proteinuria degree were significantly higher in the group with BKVN. In order to reduce the dose of immunosuppression in patients with BKVN, tacrolimus treatment was discontinued in 8 patients, and they were switched to everolimus + MMF + prednisone treatment, leflunamide + MMF + prednisone treatment in 4 patients, and sirolimus + MMF + prednisone treatment in 4 patients. The mean serum creatinine level of the patients who were followed up were observed as 1.78±0.98 mg/dl in group I.&#x0D; Conclusion: In our center, the prevalance of BKVN was found 3.92% during the study period. Reduction of dose immunosuppressive therapy is the most effective treatment. It is thought that there was no differences between Leflunamide and other approaches for treatment. Early diagnosis and screening (frequently intervals) seems to be most effective way for BKVN.

Urinary cell mRNA profiling of kidney allograft recipients: Development of a portable protocol for noninvasive diagnosis of T cell mediated rejection and BK virus nephropathy

BackgroundWe developed urinary cell mRNA profiling for noninvasive diagnosis of acute T cell mediated rejection (TCMR) and BK virus nephropathy (BKVN), two significant post-transplant complications. Our profiling protocol for the multicenter Clinical Trial of Transplantation-04 (CTOT-04) study consisted of centrifugation of urine to prepare cell pellets, washes, addition of an RNA preservative, storage at 800C and shipment in cold containers to our Gene Expression Monitoring (GEM) Core for RNA isolation and quantification of mRNA in RT-qPCR assays. To simplify profiling, we developed a filter-based protocol (ZFBP) that eliminated the need for centrifugation, RNA preservative, storage at 800C, and shipment in cold containers for mRNA profiling. Furthermore, we trained kidney allograft recipients to perform the filtration of urine at home using the filter and post the urinary cell lysate containing the RNA at ambient temperature to our GEM Core for profiling. Here, we report our refinement of ZFBP and investigation of its diagnostic performance characteristics. MethodsTotal RNA was isolated from kidney allograft biopsy-matched urines using a filter-based protocol complemented by a silica-membrane-based cartridge for mRNA enrichment, the Weill Cornell Hybrid Protocol (WCHP). Absolute copy numbers of CD3ε mRNA, CXCL10 mRNA, and 18S rRNA, components of the CTOT-04 three-gene TCMR diagnostic signature, and urinary cell BKV VP 1 mRNA copy number were measured using RT-qPCR assays. Mann-Whitney test, Fischer exact test, and receiver operating characteristic (ROC) curve analysis were used for data analyses. ResultsUrinary cell three-gene TCMR diagnostic signature scores in urines processed using the WCHP discriminated kidney allograft recipients with TCMR (12 TCMR biopsies from 11 patients) from those without TCMR or BKVN (29 No TCMR/No BKVN biopsies from 29 patients). The median (25th and 75th percentiles) score of the CTOT-04 three-gene TCMR diagnostic signature was −0.448 (−1.664, 0.204) in the TCMR group and − 2.542 (−3.267, −1.365) in the No TCMR/ No BKVN group (P = 0.0005, Mann-Whitney test). ROC curve analysis discriminated the TCMR group from the No TCMR/ No BKVN group; the area under the ROC curve (AUROC) was 0.84 (95% Confidence Intervals [CI], 0.69 to 0.98) (P < 0.001), and TCMR was diagnosed with a sensitivity of 67% (95% CI, 35 to 89) at a specificity of 86% (95% CI, 67 to 95) using the CTOT-04 validated cutpoint of −1.213 (P = 0.0016, Fisher exact test). BKV VP1 mRNA copy number in urines processed using the WCHP discriminated patients with BKVN (n = 7) from patients without TCMR or BKVN (n = 29) and the AUROC was 1.0 (95% CI, 1.00 to 1.00) (P < 0.0001) and BKVN was diagnosed with a sensitivity of 86% (95% CI, 42 to 99) at a specificity of 100% (95% CI, 85 to 100) with the previously validated cutpoint of 6.5 × 108 BKV-VP1 mRNA copies per microgram of RNA (P < 0.0001, Fisher exact test). ConclusionUrine processed using the WCHP predicted TCMR and BKVN in kidney allograft recipients. WCHP represents not only a significant advance toward the portability of urinary cell mRNA profiling but also improved patient management by minimizing their visits for urine collection.

Development of de novo donor-specific antibodies in renal transplant recipients with BK viremia managed with immunosuppression reduction.

Reduction of immunosuppression (IS) upon detection of Polyomavirus (BK) viremia is widely used to prevent BK virus nephropathy. This retrospective case-control study assesses the frequency of de novo donor-specific antibodies (dnDSA) in renal transplant recipients with IS modulation due to BK viremia and the associated risk of antibody mediated rejection. Our cohort included recipients of kidney transplantation between 2007 and 2017 with clinical, HLA antibody, and biopsy data. BK positivity was defined as viremia >10000 c/ml or biopsy proven BK nephropathy. A total of 190 BK cases matched our inclusion criteria, each case was matched with two controls based on gender, donor type, and transplant within 1 year (N = 396). Despite lower number of HLA antigen mismatches (mean = 3.5vs. 4.4, p < .001), dnDSA rates were higher in BK cases than in control group (22.1%vs. 13.9%, p = .02), with the majority detected following IS reduction for BK infection, and arising earlier posttransplant compared with no BK infection (294d vs. 434d, p < .001). Antibody mediated rejection rates were similar between cases and controls (8.9% and 8.3%, respectively), but rejection was more likely to occur earlier posttransplant in the BK cases (354d vs. 602d, p = .03). Our data suggest a link between IS reduction and the generation of dnDSA and/or rejection, supporting close monitoring for DSA in patients with reduced IS due to BK infection given their increased risk to develop dnDSA.

The pathologic spectrum of adenovirus nephritis in the kidney allograft

Adenovirus nephritis (ADVN) is a rare and understudied complication of kidney transplantation. Unlike BK virus nephropathy (BKVN), our knowledge of clinicopathologic manifestations of ADVN remains rudimentary and essentially limited to case reports. To expand on this, we retrospectively studied 11 kidney transplant recipients with ADVN and compared their allograft biopsies to 33 kidney transplant recipients with BKVN using conventional microscopy and the 770 gene Nanostring Banff Human Organ Transplant Profiling Panel. Patients with ADVN had a median age of 44 years, were predominantly male, and developed ADVN at a median of 31 months post-transplantation. Eight patients presented with fever and ten had hematuria. The most common histologic manifestations included granulomas (82%), tubulocentric inflammation (73%), and tubular degenerative changes consistent with acute tubular necrosis (73%). During a median follow-up of 55 months after biopsy, three patients developed allograft failure from subsequent acute rejection. All seven patients with available follow-up PCR showed resolution of viremia at a median of 30 days after diagnosis. Compared to BKVN, ADVN demonstrated more granulomas and less tubulointerstitial scarring. On follow-up, patients with ADVN had more rapid clearance of viral DNA from plasma. Transcriptomic analyses showed that ADVN had increased expression of several pro-inflammatory transcriptomes, mainly related to innate immunity, was associated with increased expression of transcripts with inhibitory effects on inflammatory response and showed higher enrichment with neutrophils, which can cause aggressive but short-lasting damage. Thus, we demonstrate that, despite its association with aggressive neutrophil-rich inflammation, ADVN does not often lead to allograft failure. Hence, preventing subsequent acute rejection following resolution of ADVN may improve allograft survival.

Urine exosomal bkv-miR-B1-5p and BK virus nephropathy in kidney transplant recipients

Su Woong Jung, Won-Hee Cho, Jung-Woo Seo, Jin Sug Kim, Chan-Duck Kim, Byung Ha Chung, Jae Berm Park, Yeong Hoon Kim, Sang-Ho Lee. Korean J Transplant 2022;36:254. https://doi.org/10.4285/ATW2022.F-3946

Impact of BK Polyomavirus Plasma Viral Load in Kidney Transplant Outcomes

BK polyomavirus infection (BKVi) is an important cause of kidney transplant (KT) loss, but there is scarce evidence on the impact of BK plasma viral load on graft function and long-term KT survival. A retrospective cohort study including all KT recipients with BKVi (BK viremia identified in ≥3 consecutive samples by polymerase chain reaction) in our center from January 2010 to December 2020 was performed. A case-control study (1:2) was performed. We grouped the cases according to their highest peak viral load: low-level viremia (<10,000 copies/mL) and high-level viremia (≥10,000 copies/mL). To identify risk factors for BKVi, a logistic regression analysis was achieved, and a multivariable Cox regression was used to describe risk factors for graft loss. A total of 849 KTs were performed, and 67 presented BKVi (low-level viremia, n=35 and high-level viremia, n=26). In logistic regression analysis male sex (odds ratio [OR], 4.226; 95% CI, 1.660-10.758, P=.002), age (OR, 1.047; 95% CI, 1.008-1.088; P=.018), and retransplant (OR, 4.162; 95% CI, 1.018-17.015; P=.047) were predictors of BKVi. Acute rejection was more frequent in the BKVi group (18% vs 4.9%, P=.004), and graft survival was lower in patients with BKVi and high-level viremia (P=.027). In Cox regression analysis, BKVi (hazard ratio, 3.657; 95% CI, 1.146-11.670; P=.029) and specific BKV (BK polyomavirus) high-level viremia (hazard ratio, 1.988; 95% CI, 1.012-3.907; P=.046) were predictors of shorter graft survival. BKV high-level viremia was associated with BKV nephropathy and poorer graft survival. Additionally, acute rejection is more frequent after BKVi. It is necessary to develop strategies safe and effective for these patients.

BK Virus Nephropathy of Native Kidney After Hematopoietic Stem Cell Transplantation

BK Virus Nephropathy of Native Kidney After Hematopoietic Stem Cell Transplantation

Native BK Polyomavirus Nephropathy in an Orthotopic Heart Transplant Recipient

Native BK Polyomavirus Nephropathy in an Orthotopic Heart Transplant Recipient

Comparison of BK virus nephropathy risk between double-J-stent with anti-reflux mechanism and standart double-J-stent: single-center experience

Aim: Ureteral stend use is a risk factor for BK nephropathy (BKVN). In 2015, we compared the patients with anti-reflux mechanism DJS (ARD-DJS) and those used standard DJS (st-DJS) in terms of BKV and BKVN frequency in 90 kidney transplant patients in two centers. With the increase in the number of our patients over time and lengthening of the follow-up duration, we needed to re-evaluate the data in one center. Material and Method: We retrospectively evaluated 211 patients who underwent kidney transplantation at Gazi Yaşargil Training and Research Hospital between September 2012 and September 2019. The following parameters were recorded, demographic data, immunosuppression protocols, presence of rejection, graft loss, plasma BKV levels, and presence of BKVN. Median and IQR follow-up time for ARD-DJS and St-DJS patients was 72 months (62,5-80,3 months) and 27,8 months (17,4-39,6 months) respectively. Results: Thirteen patients (6,1%) had BKV viremia. BKVN was revealed by kidney biopsy in 3 of 13 patients. However, graft loss due to BKVN was observed in only one patient. ARD-DJS was used in 4 of these cases and standard DJS was used in 9 of these cases. Patients in whom BKV revealed in the first 3 months were compared in the aspect of DJS technique, BKV was significantly less observed in the ARD-DJS group (ARD-DJS: 2 patients; St-DJS:9 patients), (p=0,046). Conclusion: In our study, BKV was observed less in patients with ARD-DJS that were clinically significant but not statistically significant. Therefore, prospective randomized studies with high patient numbers are needed to determine the effectiveness of ARD-DJS.

POS-115 IMPACT OF EARLY SCREENING FOR BK VIRURIA ON ALLOGRAFT OUTCOME AT ONE YEAR IN KIDNEY TRANSPLANT RECIPIENTS: A SINGLE-CENTER EXPERIENCE

BK virus nephropathy (BKVN) is a potential cause of renal allograft dysfunction and loss in kidney transplantation recipients (KTR). BK viruria (BKVu) occurs in 30-40% of the KTR, while BK viremia (BKVb) and BKVN occur in approximately 13% and 8%, respectively. High-level BKVu can progress to BKVb, and BKVN. Early screening for BKVu and reduction in immunosuppression in BKVu positive patients may prevent the progression to BKVN and may improve long-term patient and allograft outcomes.