Cell-Free Mitochondrial DNA: An Upcoming Non-Invasive Tool for Diagnosis of BK Polyomavirus-Associated Nephropathy.

Mitochondria are essential organelles that possess their own DNA. Mitochondrial dysfunction has been revealed in many kidney diseases, including BK polyomavirus-associated nephropathy (BKPyVAN). In this study, we introduce an innovative approach for non-invasive monitoring of mitochondrial impairment through urinary donor-derived cell-free mitochondrial DNA (ddcfmtDNA), addressing the crucial challenge of BKPyVAN diagnosis. Urinary samples were collected at the time of biopsy from a total of 60 kidney transplant recipients, comprising 12 with stable function, 22 with T cell-mediated rejection, and 21 with biopsy-proven BKPyVAN. Our findings reveal that the ddcfmtDNA-to-ddcfDNA ratio exhibits superior capability in distinguishing BKPyVAN from other conditions, with a cutoff value of 4.96% (area under curve = 0.933; sensitivity: 71.4%; and specificity: 97.1%). Notably, an elevation of ddcfmtDNA levels is associated with mitochondrial damage, as visualized through electron microscopy. These results underscore the promise of non-invasive monitoring for detecting subtle mitochondrial damage and its potential utility in BKPyVAN diagnosis. Further investigations are required to advance this field of research.

Effect of steroid pulses in severe BK virus allograft nephropathy with extensive interstitial inflammation.

INTRODUCTION: As there is no specific antiviral treatment currently available for BK polyomavirus associated nephropathy (BKVAN), its management relies on immunosuppression reduction in kidney transplant patients. Data on efficacy of steroid pulses in this indication are lacking. METHODS: We performed a retrospective monocenter study on 64 patients diagnosed with biopsy-proven BKVAN. Patients within the "pulse group" (n = 37) received IV methylprednisolone 10 mg/kg 3 days consecutively. In the "low dose" steroid group (n = 27), patients were continued oral prednisone 5 mg daily. RESULTS: Mean follow up was 78 months in the steroid pulse group and 56 months in the low dose group (p = 0.15). Mean eGFR values at diagnosis were comparable, as well as other demographic characteristics. Mean BK plasma viral load was higher in "pulse" than in "low dose" steroid group. Pulse group had higher inflammation and tubulitis (p < 0.05). Graft loss reached 57% in the "pulse" group versus 41% in the "low dose" group, p = 0.20. Rejection events were similar. No major adverse event was statistically associated with steroid pulse, including infections, cancer, and de novo diabetes. CONCLUSION: No significant differences were found in the evolution of both groups of patients, despite patients receiving "pulse" steroids were identified as the most severe sharing higher BK viral load and more frequent active lesions on histology.

Impact of BK polyomavirus viremia on the outcomes of allogeneic hematopoietic stem cell transplantation.

Although it is known that BK polyomavirus (BKPyV) causes hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT), the clinical significance of BKPyV viremia has not been fully evaluated. We retrospectively analyzed the results of quantitative polymerase chain reaction (PCR) evaluations for detecting BKPyV in the whole blood samples of patients undergoing allogeneic HSCT during the period from January 2010 to June 2020 at a single institute, Tokyo Medical and Dental University. BKPyV was detected in the blood of 28 of the 107 evaluated patients, and the cumulative incidence of was 27.9% (95%CI: 20.2-37.9%). HC due to BKPyV developed in four of the 28 patients with BKPyV viremia (14.3%) and in two of the 79 patients without it (2.5%; P < 0.05). BKPyV viremia itself did not affect the patients' post-transplant estimated glomerular filtration rate (eGFR), but BKPyV viremia with a high viral load was significantly associated with decreased eGFR values (P < 0.05). BKPyV viremia was also associated with significantly lower progression-free survival at 3 years (35.1% [95%CI: 17.8-53.1%] vs. 60.4% [95%CI: 48.4-70.5], P < 0.05). Our findings demonstrated that BKPyV viremia was associated with onset of HC, an early decline of renal function, and poorer survival after allogeneic HSCT. Further studies are needed to test these results and elucidate the mechanisms of renal dysfunction associated with BKPyV viremia.

Impact of BK Polyomavirus NCCR variations in post kidney transplant outcomes.

The human BK Polyomavirus (BKPyV) is a DNA virus that is prevalent in 80 % of the population. Infection with this virus may begin in childhood, followed by asymptomatic persistence in the urinary tract. However, in immunocompromised individuals, especially kidney transplant recipients (KTRs), heightened replication of BKPyV can lead to severe complications. The genome of this virus is divided into three parts; the early and late region, and the non-coding control region (NCCR). Mutations in the NCCR can change the archetype strain to the rearranged strain, and NCCR rearrangements play a significant in virus pathogenesis. Interestingly, diverse types of NCCR block rearrangement result in significant differences in conversion potential and host cell viability in the infected cells. A correlation has been detected between increased viral replication potential and pathogenesis in BKPyV-infected KTRs with specific NCCR rearrangements. The objective of this review study was to examine the disease-causing and clinical consequences of variations in the NCCR in BKPyV-infected KTRs such as virus-associated nephropathy (BKPyVAN).

Performance evaluation of the high-throughput quantitative Alinity m BK virus assay.

BK virus (BKV) infection or reactivation in immunocompromised individuals can lead to adverse health consequences including BKV-associated nephropathy (BKVAN) in kidney transplant patients and BKV-associated hemorrhagic cystitis (BKV-HC) in allogeneic hematopoietic stem cell transplant recipients. Monitoring BKV viral load plays an important role in post-transplant patient care. This study evaluates the performance of the Alinity m BKV Investigational Use Only (IUO) assay. The linearity of the Alinity m BKV IUO assay had a correlation coefficient of 1.000 and precision of SD ≤ 0.25 Log IU/mL for all panel members tested (2.0-7.3 Log IU/mL). Detection rate at 50 IU/mL was 100%. Clinical plasma specimens tested comparing Alinity m BKV IUO to ELITech MGB Alert BKV lab-developed test (LDT) on the Abbott m2000 platform using specimen extraction protocols for DNA or total nucleic acid (TNA) resulted in coefficient of correlation of 0.900 and 0.963, respectively, and mean bias of 0.03 and -0.54 Log IU/mL, respectively. Alinity m BKV IUO compared with Altona RealStar BKV and Roche cobas BKV assays demonstrated coefficient of correlation of 0.941 and 0.980, respectively, and mean bias of -0.47 and -0.31 Log IU/mL, respectively. Urine specimens tested on Alintiy m BKV IUO and ELITech BKV LDT using TNA specimen extraction had a coefficient of correlation of 0.917 and mean bias of 0.29 Log IU/mL. The Alinity m BKV IUO assay was performed with high precision across the dynamic range and correlated well with other available BKV assays. IMPORTANCE: BK virus (BKV) in transplant patients can lead to adverse health consequences. Viral load monitoring is important in post-transplant patient care. This study evaluates the Alinity m BKV assay with currently available assays.

Prevalence of BK and JC Polyomaviruses among Patients with Breast Cancer.

INTRODUCTION: Breast cancer, a pervasive invasive carcinoma among women globally, afflicts approximately 12% of women worldwide. Previous studies have indicated that certain viruses, including oncogenic viruses such as polyomaviruses BK and JC, may play a role in the development of breast cancer. In light of this, the present study endeavors to assess the incidence of BKV and JCV virus in breast cancer patients. MATERIALS AND METHODS: One hundred formalin-fixed paraffin-embedded tissue samples were procured and subjected to deparaffinize by xylene, followed by DNA extraction through the phenol-chloroform methodology. Detection and genotyping of BKV and JCV were carried out utilizing specific primers via PCR analysis. RESULTS: Merely 2 out of 100 (2%) ductal carcinoma in situ with grade 2 specimens exhibited positivity for BK virus genotype IV, whereas JC virus DNA was not discerned across all the samples. DISCUSSION: The findings of the current investigation demonstrate that there was an absence of JC virus detection in the breast biopsy. Additionally, a small fraction of patients diagnosed with ductal carcinoma exhibited a low prevalence of genotype IV polyomavirus BK at a rate of 2%. However, in order to gain a more comprehensive understanding of the incidence of BKV and JCV in breast cancer, a substantial number of breast samples must undergo investigation.

Safety and efficacy of a reduced frequency viral monitoring strategy for Epstein-Barr virus, cytomegalovirus, and BK polyomavirus post-kidney transplant: A quality assurance initiative.

BACKGROUND: There is variability in recommended viral monitoring protocols after kidney transplant. In response to increased demand for laboratory testing during the COVID-19 pandemic, the Transplant Manitoba Adult Kidney Program updated its monitoring protocols for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and BK polyomavirus (BKV) to a reduced frequency. METHODS: This single-center nested case-control study evaluated 252 adult kidney transplant recipients transplanted from 2015 to 2021, with the updated protocols effective on March 19th 2020. Cases included recipients transplanted after the protocol update who developed CMV, EBV, and BKV DNAemia and were matched to controls with DNAemia transplanted prior to the protocol update. The primary outcome was the difference in maximum DNA load titers between cases and matched controls. Secondary outcomes included time to initial DNAemia detection and DNAemia clearance. Safety outcomes of tissue-invasive viral disease were described. RESULTS: There were 216 recipients transplanted preupdate and 36 recipients postupdate. There was no difference between cases and controls in maximum or first DNA load titers for EBV, CMV, or BKV. Cases experienced earlier EBV DNAemia detection (26 (IQR 8, 32) vs. 434 (IQR 96, 1184) days, p = .005). Median follow-up was significantly longer for recipients transplanted preupdate (4.3 vs. 1.3 years, p < .0001). After adjusting for follow-up time, there was no difference in DNAemia clearance or tissue-invasive viral disease. CONCLUSION: Our findings suggest that reduced frequency viral monitoring protocols may be safe and cost-effective. This quality assurance initiative should be extended to detect longer-term and tissue-invasive disease outcomes.

The value and complexity of studying cellular immunity against BK Polyomavirus in kidney transplant recipients.

BK Polyomavirus is of particular concern for kidney transplant recipients, due to their immunosuppression. This problem is exacerbated by the high effectiveness of antirejection therapies, which also compromise the organism's ability to fight viral infections. The long-term risk is loss of graft function through BKPyV-associated nephropathy (BKPyVAN). The assessment of host immunity and its link to the control of viral infections is a major challenge. In terms of humoral immunity, researchers have highlighted the prognostic value of the pre-transplantation anti-BKPyV immunoglobulin G titer. However, humoral immunity alone does not guarantee viral clearance, and the correlation between the humoral response and the time course of the infection remains weak. In contrast, cellular immunity variables appear to be more closely associated with viral clearance, given that the cellular immune response to the kidney transplant is the main target of immunosuppressive treatments in recipients. However, the assessment of the cellular immune response to BK Polyomavirus is complex, and many details still need to be characterized. Here, we review the current state of knowledge about BKPyV cellular immunity, as well as the difficulties that may be encountered in studying it in kidney transplant recipient. This is an essential area of research for optimizing the management of transplant recipients and minimizing the risks associated with insidious BKPyV disease.

A multicenter prospective study to define the natural history of BK viral infections in kidney transplantation.

BACKGROUND: BK polyomavirus (BKV) can cause permanent loss of allograft function due to BKV-associated nephropathy (BKVN) in kidney transplant recipients. Besides immunosuppression reduction, there are no consistently effective interventions for BKV infection. Study purpose was to define natural history of BKV infection, identify risk factors for BKV reactivation and BKVN in kidney transplant recipients, and inform the design/conduct of future clinical trials of BKV-targeted therapeutics. METHODS: We conducted a multicenter prospective observational study of incident kidney transplant recipients at six U.S. transplant centers. Participants were monitored every 4 weeks for BKV reactivation and followed for up to 24 months post-transplant. We used regression models (logistic, survival, mixed models) to study relationships between BK viremia/BKVN, clinical characteristics, and allograft function. RESULTS: We enrolled 335 participants. Fifty-eight (17%) developed BK viremia, 6 (2%) developed biopsy-proven BKVN, and 29 (9%) developed suspected/presumed BKVN (defined as BKV viral load > 10,000 copies/mL without biopsy). Male donor sex was associated with lower odds for BK viremia, whereas recipient Black race was associated with two-fold increased odds for BK viremia. Recipient female sex was associated with more rapid clearance of BK viremia. Persistent BK viremia/BKVN was associated with poorer allograft function by 24 months post-transplant. CONCLUSIONS: We identified multiple donor and recipient demographic factors associated with risk for BKV infection and poorer allograft function by 24 months post-transplant. This may help design future clinical trials of therapies to prevent or mitigate the deleterious impact of BKV reactivation on kidney transplant outcomes.

The risk factors associated with post-transplantation BKPyV nephropathy and BKPyV DNAemia: a prospective study in kidney transplant recipients.

BACKGROUND: BK polyomavirus (BKPyV) infection after kidney transplantation can lead to serious complications such as BKPyV-associated nephropathy (BKPyVAN) and graft loss. The aim of this study was to investigate the incidence of BKPyVAN after implementing a BKPyV screening program, to map the distribution of BKPyV genotypes and subtypes in the Uppsala-Örebro region and to identify host and viral risk factors for clinically significant events. METHODS: This single-center prospective cohort study included kidney transplant patients aged ≥ 18 years at the Uppsala University Hospital in Sweden between 2016 and 2018. BKPyV DNA was analyzed in plasma and urine every 3 months until 18 months after transplantation. Also genotype and subtype were determined. A logistic regression model was used to analyze selected risk factors including recipient sex and age, AB0 incompatibility and rejection treatment prior to BKPyVAN or high-level BKPyV DNAemia. RESULTS: In total, 205 patients were included. Of these, 151 (73.7%) followed the screening protocol with 6 plasma samples, while184 (89.8%) were sampled at least 5 times. Ten (4.9%) patients developed biopsy confirmed BKPyVAN and 33 (16.1%) patients met criteria for high-level BKPyV DNAemia. Male sex (OR 2.85, p = 0.025) and age (OR 1.03 per year, p = 0.020) were identified as significant risk factors for developing BKPyVAN or high-level BKPyV DNAemia. BKPyVAN was associated with increased viral load at 3 months post transplantation (82,000 vs. < 400 copies/mL; p = 0.0029) and with transient, high-level DNAemia (n = 7 (27%); p < 0.0001). The most common genotypes were subtype Ib2 (n = 50 (65.8%)) and IVc2 (n = 20 (26.3%)). CONCLUSIONS: Male sex and increasing age are related to an increased risk of BKPyVAN or high-level BKPyV DNAemia. BKPyVAN is associated with transient, high-level DNAemia but no differences related to viral genotype were detected.

Efficacy of mTOR Inhibitors and Intravenous Immunoglobulin for Treatment of Polyoma BK Nephropathy in Kidney Transplant Recipients: A Biopsy-Proven Study.

OBJECTIVES: We investigated the efficacy of a predetermined protocol that consisted of immunosuppressive drug reduction/withdrawal and intravenous immunoglobulin administration for the treatment of polyoma BK virus nephropathy. MATERIALS AND METHODS: Patients with biopsy-proven polyoma BK virus nephropathy received a treatment regimen based on discontinuation of both calcineurin inhibitors and antiproliferative agents and switching to mTOR inhibitors accompanied by intravenous immunoglobulin administration. RESULTS: Our study included 508 patients, with polyoma BK viremia detected in 80 patients. The mean age was 45.3 ± 9.5 years (range, 18-71 y), 64% were male, and mean follow-up was 37 ± 21 months (6-94 mo). All 16 patients who developed polyoma BK virus nephropathy and 9 patients who had highgrade polyoma BK viremia without nephropathy received intravenous immunoglobulin treatment. Compared with patients with viremia, patients with polyoma BK virus nephropathy had significantly higher rates of graft loss due to rejection (18.8% vs 1.6%; P = .024) and all-cause graft loss (31.2% vs 6.3%; P = .014). Histopathologically, viral inclusion bodies disappeared and SV40 became negative after treatment in all 13 patients who underwent protocol biopsies. Unfortunately, histopathologically complete recovery without chronic tubular and interstitial tissue damage was achieved in only 4 patients after treatment. In addition, 3 patients lost their grafts due to acute antibody-mediated or mixed-type rejection (18.8%). CONCLUSIONS: In patients with polyoma BK virus nephropathy, clearance of viremia and SV40 should not be the sole outcomes to obtain. Aggressive reductions in maintenance immunosuppression and switching to double-drug therapy combined with high-dose intravenous immunoglobulin leads to high rates of graft loss/rejection and sequalae of chronic histological changes.

AIDS-Associated BK Virus Nephropathy in Native Kidneys: A Case Report and Review of the Literature.

BK virus (BKV) is a small DNA virus, a member of the polyomavirus family, that causes an opportunistic infection in immunocompromised patients, especially kidney transplant patients. This virus establishes a lifelong infection in most of the population, and once it reactivates in an immunocompromised state, leads to BKV nephropathy. This review seeks to assess the correlation between severe immunosuppression, evident by low CD4 cell counts in HIV-positive patients, and the reactivation of BKV, causing nephropathy. A literature review was conducted, extracting, and analyzing case reports of HIV-positive patients showing correlations between their degree of immunosuppression, as evidenced by their CD4 counts, and the degree of BKV infectivity, confirmed by kidney biopsy. A total of 12 cases of BKV nephropathy in HIV-infected patients were reviewed. A common finding was the presence of profound immunosuppression, with most patients having CD4 counts ≤50 cells/ mm3. A substantial number also had comorbid malignancies, with some undergoing chemotherapy, potentially increasing the risk of BKV reactivation. In addition to the HIV status and malignancies, other risk factors for BKV reactivation included older age, male gender, diabetes mellitus, Caucasian race, and ureteral stent placement. BKV nephropathy in HIV patients with native kidneys is closely correlated with severe immunosuppression. Although therapeutic strategies exist for post-transplant patients, aside from the treatment of HIV with highly active anti-retroviral therapy (HAART), which potentially helps with clearing BKV by increasing CD4 count, there is no definitive treatment for a native kidney BKV nephropathy in patients with AIDS. The complexity of the cases and severity of comorbidities indicate the need for further research to develop therapeutic strategies tailored to this population.

Accuracy of quantitative viral secondary standards: a re-examination.

Interlaboratory agreement of viral load assays depends on the accuracy and uniformity of quantitative calibrators. Previous work demonstrated poor agreement of secondary cytomegalovirus (CMV) standards with nominal values. This study re-evaluated this issue among commercially produced secondary standards for both BK virus (BKV) and CMV, using digital polymerase chain reaction (dPCR) to compare the materials from three different manufacturers. Overall, standards showed an improved agreement compared to prior work, against nominal values in both log10 copies/mL and log10 international unit (IU)/mL, with bias from manufacturer-assigned nominal values of 0.0-0.9 log10 units (either copies or IU)/mL. Standards normalized to IU and those values assigned by dPCR rather than by real-time PCR (qPCR) showed better agreement with nominal values. The latter reinforces prior conclusions regarding the utility of using such methods for quantitative value assignment in reference materials. Quantitative standards have improved over the last several years, and the remaining bias from nominal values might be further reduced by universal implementation of dPCR methods for value assignment, normalized to IU. IMPORTANCE: Interlaboratory agreement of viral load assays depends on accuracy and uniformity of quantitative calibrators. Previous work, published in JCM several years ago, demonstrated poor agreement of secondary cytomegalovirus (CMV) standards with nominal values. This study re-evaluated this issue among commercially produced secondary standards for both BK virus (BKV) and CMV, using digital polymerase chain reaction (dPCR) to compare the materials from three different manufacturers. Overall, standards showed an improved agreement compared to prior work, against nominal values, indicating a substantial improvement in the production of accurate secondary viral standards, while supporting the need for further work in this area and for the broad adaption of international unit (IU) as a reporting standard for quantitative viral load results.

Analysis of early clinical signs and risk factors for severe hemorrhagic cystitis after stem cell transplantation in children.

INTRODUCTION: To analyze the characteristics of early clinical symptoms of hemorrhagic cystitis (HC) after hematopoietic stem cell transplantation (HSCT) and the risk factors of severe HC. METHODS: We retrospectively analyzed 77 children with post-HSCT HC treated at our hospital between June 2013 and June 2021. Clinical characteristics were collected and catalogued. RESULTS: Among the children with urinary tract irritation symptoms (UTIS) as the first symptom, symptoms appeared earlier than hematuria symptoms (28 day vs. 31 day, p = 0.027), and the time progressing to severe HC was significantly longer in these children (12 day vs. 7 day, p = 0.038), but there was no significant difference in the number of participants (57.8% vs. 59.4%, p = 0.889). BK polyomavirus (BKV) infection was an independent risk factor (hazard ratio [HR] = 2.782, p = 0.035) for severe HC, which was also positively associated with multi-viral infection (HR = 2.215, p = 0.020). CONCLUSIONS: In HC children, when the first urinary tract symptom was UTIS, it appeared earlier than hematuria, and the time of progression to severe HC was significantly longer, suggesting that we still need more aggressive treatment for these children to prevent the worsening of symptoms. The severity of HC was positively correlated with BKV infection and multiple infections.

Visual, rapid, and cost-effective BK virus detection system for renal transplanted patients using gold nanoparticle coupled loop-mediated isothermal amplification (nanoLAMP).

A substantial percentage of kidney transplant recipients show transplant failure due to BK virus-induced nephropathy. This can be clinically controlled by the rapid and timely detection of BK virus infection in immune-compromised patients. We report a rapid (two hours from sample collection, processing, and detection), cost-effective (< 2$), highly sensitive and BKV-specific nanoLAMP (loop-mediated isothermal amplification) diagnostic methodology using novel primers and gold nanoparticles complex-based visual detection. The standardized nanoLAMP showed an analytical sensitivity of 25 copies/µl and did not cross-react with closely related JC and SV40 viruses. This nanoLAMP showed diagnostic sensitivity and specificity as 91% and 96%, respectively, taking 50 BK virus-negative (confirmed by qPCR from the plasma of healthy donors) and 57 positive BKV patient samples (confirmed by clinical parameters and qPCR assay). This simple two-step, low-cost, and quick (1-2 h/test) detection would be advantageous over the currently used diagnostic methodology. It may change the paradigm for polyomavirus infection-based failure of renal transplant.

Stability of BK polyomavirus DNA in urine over time and analytical evaluation of an automated BKV quantitative nucleic acid test.

Introduction. BK polyomavirus (BKPyV) quantitative testing is an important screening tool post-transplantation, although interpretation can be challenging due to lack of standardization, assay heterogeneity and variability of BKPyV DNA over time (in urine).Methods. Remnant clinical EDTA plasma and urine samples were tested by the cobas BKV test and a validated laboratory-developed test (LDT). Accuracy [positive and negative percent agreement (PPA and NPA), Pearson's correlation, Bland-Altman analysis] and reproducibility were evaluated. To assess BKPyV DNA stability in urine, prospective urine samples were maintained at two different storage temperatures and tested in triplicate over 7 days.Results. Overall PPA was 95.6 % (43/45) and NPA was 94.4 % (170/180). For plasma, Pearson's correlation (0.950) and Bland-Altman analysis (0.113±0.22 log10 IU ml-1) showed high agreement. For neat urine, Pearson's correlation (0.842) and Bland-Altman analysis (0.326±0.80 log10 IU ml-1) showed somewhat higher variability. Reproducibility was high for the cobas BKV versus the LDT. BKPyV DNA levels in neat urine remained relatively stable over 7 days at both storage temperatures, although outlier results were intermittently detected.Conclusion. The cobas BKV test showed high agreement and reproducibility compared to the reference LDT. BKPyV viral load testing in urine has known limitations, but neat urine can be processed by the cobas BKV.

Treatment of BK Polyomavirus-Associated Nephropathy in Paediatric Kidney Transplant Recipients: Leflunomide Versus Cidofovir.

OBJECTIVES: BK polyomavirus-associated nephropathy is a clinicopathological entity that negatively affects graft function in kidney transplant recipients. We compared the efficacy of leflunomide and cidofovir to treat BK polyomavirus-associated nephropathy in pediatric kidney transplant recipients. MATERIALS AND METHODS: Medical records of pediatric recipients with BK viremia for the period 2004 through 2019 were reviewed retrospectively, and patients diagnosed with BK polyomavirusassociated nephro-pathy were included in the study. A serum BK virus level above 104 copies/mL was accepted as BK viremia. We defined BK polyomavirusassociated nephropathy as detection of BK virus SV40 antigen on immunochemistry staining of renal graft tissue accompanied by signs of tubulointerstitial nephritis or elevated serum creatinine in addition to BK viremia. RESULTS: Of 304 kidney transplant recipients, 53 had persistent BK viremia; 36 of these patients (61.1% male) were included in the study with the diagnosis of BK polyomavirus-associated nephropathy. Twelve patients (33.3%) received cidofovir, and 14 (38.8%) received leflunomide. Results were similar between the cidofovir and leflunomide groups for serum creatinine level at last follow-up (0.91 ± 0.29 vs 0.94 ± 0.37 mg/dL, respectively; P = .843) and graft failure rate (8.3% vs 14.2%, respectively; P = .632). Graft failure was observed in 8.3% of patients with BK polyomavirus-associated nephropathy. CONCLUSIONS: Leflunomide and cidofovir showed similar efficacy for treatment of BK polyomavirus-associated nephropathy.

Impact of Infection-Related Immunosuppressant Reduction on Kidney Transplant Outcomes: A Retrospective Study Considering the Temporal Dynamics of Immunosuppressive Requirements.

Immunosuppressant reduction (ISR) is a common treatment for kidney transplant recipients experiencing infections, but its impacts on kidney transplant outcomes remains unclear. This retrospective single-center study included 300 patients who underwent kidney transplantation between January 2017 and April 2020. The post-transplant timeline was divided into four distinct phases: ≤1 month, 2-6 months, 7-12 months, and >12 months. Patients were categorized based on the presence of clinically relevant infections and whether they received ISR. Significant differences were observed in the spectrum of clinically relevant infections across the post-transplant phases. During the ≤1 month phase, primary infections were associated surgical operation, such as urinary tract infections involving Enterococcus spp. and Candida spp. Cytomegalovirus and BK polyomavirus (BKPyV) infections increased during the 2-6 months and 7-12 months periods. Approximately one-third of patients experienced ISR due to infection, with BKPyV infections being the primary causes. Recipients who experienced their first ISR due to infection between 2-6 months and 7-12 months had worse graft survival comparing with patients without any infections. ISR due to infections between 2 and 6 months was associated with a higher risk of rejection. Tailored ISR strategies should be developed according to temporal dynamics of immunosuppressive intensity to prevent rejection.

The molecular footprints of BK virus in the product of conception over the second and third gestational trimesters.

OBJECTIVE: Prior studies have shown controversial results on the vertical transmission of BK virus (BKV). The present study aimed to assess the possibility of BKV vertical transmission from mother to fetus in the product of conception (embryo, fetuses, and/or placentas) over the three stages of pregnancy. RESULTS: Of the 26 placental studied tissues, 6 were in the first trimester, and none of which were positive. Only one out of the 13 (7.7%) placental materials in the second trimester was positive. Only one out of 7 (14%) placental materials of the third trimester was positive. There were cases that no virus was detected in their placental but BKV was detected in their other tissues. Among 26 conceptuses, 17 (65%) were negative for BKV and 9 (34.6%) were positive, 7/13 (54%) were positive in the second, and 2/7 (29%) were positive in the third trimester fetuses. BKV was most frequently detected in the liver (eight cases), heart (three cases), and placenta (2 cases). There were cases that no virus was detected in their placental but BKV was detected in their other tissues.