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Background and Objectives: BK polyomavirus infection is prevalent and primarily asymptomatic, except for complications in kidney transplant recipients. Furthermore, its involvement in a tumorigenic family necessitates consideration in various malignancies such as urogenital tumors, prostate cancer, colorectal cancer (CRC), and brain cancer. Materials and Methods: This investigation encompassed 50 specimens of colorectal adenocarcinoma tumors, 50 adjacent tissues, and 40 urine samples, with patients having a mean age of 61 years ± 12.4 years. The detection of BK virus DNA VP1 gene and genotyping were carried out through nested-PCR and sequencing techniques. Results: Through the utilization of nested-PCR, BK virus DNA was identified in 15/50 (30%) colorectal tumor samples and 3/50 (6%) adjacent tissues (p-value = 0.008). Additionally, 6/40 (15%) urine samples exhibited positive results for BK virus DNA. Notably, among these findings, 9/15 BK virus positive tumor tissues (60%) and 3/6 BK virus positive urine samples (50%) were confirmed to be positive for BK virus subtype 4 (p-value < 0.001), whereas 2 tumor samples and 3 urine samples were attributed to BK virus type 1b2. Conclusion: It is imperative to enhance one's understanding of the etiological and risk factors pertaining to cancers. The present findings offer substantiation of a potential correlation between BK virus infection and colorectal cancer. BK virus genotype 4 was found to be dominant among the CRC patients in this study. [ABSTRACT FROM AUTHOR]

Kidney transplant recipients require a lifelong protocol of immunosuppressive therapy to prevent graft rejection. However, these same medications leave them susceptible to opportunistic infections. One pathogen of particular concern is human polyomavirus 1, also known as BK virus (BKPyV). This virus attacks kidney tubule epithelial cells and is a direct threat to the health of the graft. Current standard of care in BK virus-infected transplant recipients is reduction in immunosuppressant therapy, to allow the patient's immune system to control the virus. This requires a delicate balance; immune suppression must be strong enough to prevent rejection, yet weak enough to allow viral clearance. We seek to model viral and immune dynamics with the ultimate goal of applying optimal control methods to this problem. In this paper, we begin with a previously published model and make simplifying assumptions that reduce the number of parameters from 20 to 14. We calibrate our model using newly available patient data and a detailed sensitivity analysis. Numerical results for multiple patients are given to show that the newer model reflects observed dynamics well. [ABSTRACT FROM AUTHOR]

Objectives: Oral cancer (OC) is the most common malignant tumor of the head and neck (HN) and ranks 16th among the most frequently diagnosed cancers worldwide. A systematic review and meta-analysis aimed to provide an evidence-based analysis of the relationship between polyomaviruses and oral cancer. Methods: The global online databases was used to identify relevant studies published between January 2000 and September 2024. The quality of each article was assessed using the Newcastle-Ottawa Scale (NOS) checklist. Data analysis was performed using STATA Ver. 11 software, and the standard error was calculated using the binomial distribution formula. The heterogeneity of the study results was assessed using the I-square and Q index, while publication bias was examined using the Begg's test. In addition, a random effects model was used to determine the risk difference (RD), and a forest plot diagram was used to present the results with 95% confidence intervals. The Trim and Fill test was applied to estimate publication bias, and sensitivity analysis was performed to assess the influence of individual studies on the overall estimate. Results: Of the nine studies, the relationship between BK virus (BKV) and the Merkel cell polyomavirus (MCV) and oral cancer was investigated. In five primary studies, and by combining the results of these studies, the risk of oral cancer in MCV and BKV-positive individuals was significantly higher than in the negative groups by 13% (RD: 0.13, 95% CI: 0.00, 0.26) and 2% (RD: 0.02, 95% CI: -0.03, 0.07), respectively. In addition, the association between JC virus (JCV) and oral cancer was investigated in six primary studies. By combining the results of these studies, the risk of oral cancer in JCV-positive individuals was 1% higher than that in JCV-negative individuals (RD: 0.01, 95% CI: -0.02, 0.06). Discussion: This meta-analysis showed that there was a significant association between MCV and oral cancer, and the risk of oral cancer in MCV- positive individuals was 13% higher than that in MCV- negative individuals. More preliminary studies are needed on the association between BKV and JCV and the risk of oral cancer. [ABSTRACT FROM AUTHOR]

Chronic kidney disease is a really important heath issue, and transplantation is an intervention that can greatly increase patient quality of life and survival. The aim of this study was to perform a comprehensive evaluation of the BK virus, CMV, and EBV in kidney transplant recipients (KTRs); to assess the prevalence of infections; and to test if our detection method would be feasible for use in follow-ups with KTRs. A total of 157 KTRs registered at the Clinical Hospital "Dr. C. I. Parhon", Iași, Romania, were selected using specific inclusion/exclusion criteria. We tested the blood samples from each patient for BK, EBV, and CMV using a multiplex real-time PCR (qPCR) assay and the TaqMan PCR principle. The highest prevalence was detected for BKV (11/157, 7%), followed by CMV (9/157, 5.7%) and EBV (5/157, 3.2%). By simultaneously detecting three possible nephropathic viruses and oncogenes in KTRs using multiplex real-time PCR, we aimed to optimize their monitoring and follow-up. The prevalence of the tested nephropathogenic viruses—BKV, CMV, and EBV—was comparable to that analyzed in other studies. We demonstrate that the use of qPCR for viral detection in KTRs is a robust, cost-effective method for case monitoring. [ABSTRACT FROM AUTHOR]

The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN. 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman's correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission. In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766. FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233. [ABSTRACT FROM AUTHOR]

This study aims to investigate the incidence and prognosis of malignancy in individuals with thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous nephropathy (MN). First, we performed a systematic literature review of prevalence of malignancy in THSD7A-associated MN. Then, we conducted a retrospective analysis of 454 patients diagnosed with MN through renal biopsy at our hospital between January 2016 and December 2020. We assessed the presence of serum anti-THSD7A antibodies and performed immunohistochemical staining of renal tissue for THSD7A. Subsequently, we followed patients with THSD7A-associated MN for a minimum of 3–5 years, collecting their clinical, pathological characteristics, and prognosis. Additionally, we conducted a literature review on patients with THSD7A-associated MN in conjunction with malignancy. We identified a total of nine articles containing comprehensive data on THSD7A-associated MN and malignancy. Among 235 patients with THSD7A-positive MN, 36 individuals had concurrent malignancies, resulting in a malignancy prevalence of 13.3% (95% CI: 8.9–17.7%). In our center, we followed up with 15 patients diagnosed with THSD7A-associated MN and observed three cases of concomitant tumors: two cases of lung adenocarcinoma and one case of small cell lung cancer with multiple metastases. The prevalence of malignancy in our cohort was 20%. Notably, we detected positive THSD7A staining in both renal and lung cancer tissues in one patient with small cell lung cancer. Patients with THSD7A-associated MN should undergo vigilant follow-up assessments, with a particular focus on actively seeking potential tumorigenic lesions to prevent misdiagnosis or oversight. [ABSTRACT FROM AUTHOR]

This retrospective study aims to investigate the prevalence and immunopathologic characteristics of seropositive and seronegative hepatitis B virus-associated membranous nephropathy (HBV-MN). Clinicopathologic and serologic records of 420 patients with histologically confirmed HBV-MN between January 2014 and July 2021 were examined to determine the prevalence of seropositive and seronegative HBV-MN. Serum anti-PLA2R antibody testing was conducted on 280 patients with HBV-associated membranous nephropathy (HBV-MN) from August 2018 to July 2021. Immunopathologic characteristics of HBV-MN patients and anti-PLA2R antibody positivity were analyzed. Among 420 pathologically confirmed HBV-MN patients, 230 (54.8%) were seropositive for HBV. The seropositive group exhibited higher blood creatinine values and incidence of liver function abnormalities than the seronegative group (p <.05). Serum anti-PLA2R antibody testing on 280 HBV-MN patients revealed a total positive rate of 44.6%, with the seronegative group showing a significantly higher rate (62.6%) compared to the seropositive group (32.1%) (p <.01). The anti-PLA2R antibody-positive group displayed higher levels of urine protein (p <.05), serum cholesterol (p <.01), and IgG4 subtypes (p <.05) compared to the negative group. Additionally, the positive group had significantly lower levels of serum albumin and IgG than the negative group (p <.01). This comprehensive study reveals a significantly higher prevalence of seronegative HBV-MN than previously thought. The blood creatinine values and incidence of liver function abnormalities was higher in the serology-positive group than in the serology-negative group. Notably, the seronegative group displayed a higher positive rate of anti-PLA2R antibodies compared to the seropositive group, indicating distinctive clinical and immunopathologic features. [ABSTRACT FROM AUTHOR]

BK viremia (BKPyV-DNAemia) and nephropathy (BKPyVAN) are significant causes of morbidity and mortality in kidney transplant recipients (KTRs). Vitamin D supports immune function, yet low 25-hydroxyvitamin D [25(OH)D] is common among KTRs. The association between serum 25(OH)D, measured 61 days to 2 years post-transplant, and subsequent incident BKPyV-DNAemia and BKPyVAN was examined in KTRs without previous BKPyV-DNAemia or BKPyVAN, respectively. Out of 3308 KTRs, 399 (12%) were vitamin D deficient [25(OH)D ≤ 20 ng/mL], and 916 (27.7%) were insufficient [25(OH)D 21–29 ng/mL]. A total of 184 KTRs developed BKPyV-DNAemia and 44 developed BKPyVAN. The incidence rate (/100 person-years) for BKPyV-DNAemia was 2.88 in the 25(OH)D sufficient group, 2.22 in the insufficient group, and 2.37 in the deficient group. The incidence rate (/100 person-years) for BKPyVAN was 0.30 in the 25(OH)D sufficient group, 0.75 in the insufficient group, and 1.28 in the deficient group. Vitamin D deficiency (adjusted hazard ratio [aHR] compared to 25(OH)D sufficiency: 3.92; 95% CI: 1.66–9.23) and insufficiency (aHR: 2.22; 95% CI: 1.11–4.45) remained significantly associated with the incidence of BKPyVAN after adjustment for baseline characteristics. Low serum 25(OH)D was associated with an increased risk of BKPyVAN but not BKPyV-DNAemia. [ABSTRACT FROM AUTHOR]

Abstract BK virus is implicated in polyomavirus-associated nephropathy (PVAN) and hemorrhagic cystitis, particularly in kidney transplant recipients, affecting the functionality of the transplanted kidney and posing a risk of graft loss. Despite these challenges, specific antiviral drugs targeting BK virus remain elusive. Agnoprotein, a small, positively charged protein encoded by the BK virus late gene, functions in the assembly, maturation, and release of the virus. Consequently, agnoprotein emerges as a promising target for potential anti-BK virus drugs. Utilizing phage display technology, we conducted screening to identify specific binding peptides against the agnoprotein. The primary objective of screening binding peptides is to utilize them to disrupt the virus’s life cycle, impeding its replication and transmission, thereby achieving antiviral effects. In the current experimental study, a combination of phage 7 peptide libraries and 12 peptide libraries was employed for screening purposes. Following four rounds of screening, seven positive phages demonstrating the ability to bind Agnoprotein were successfully isolated. Following ELISA validation, it was observed that the optical density (OD) values for Agnoprotein binding of the seven positive clones significantly exceeded three times the value of the negative control (NC). Subsequent analysis identified one 7-peptide and six 12-peptides within the binding peptides. Moreover, OD values of dodecapeptide phage clones bound to agnoprotein were generally higher than those of heptapeptide phage clones.In conclusion, our study demonstrates the successful identification of specific binding peptides against agnoprotein, a crucial component in the BK virus life cycle.

Abstract Objectives Oral cancer (OC) is the most common malignant tumor of the head and neck (HN) and ranks 16th among the most frequently diagnosed cancers worldwide. A systematic review and meta-analysis aimed to provide an evidence-based analysis of the relationship between polyomaviruses and oral cancer. Methods The global online databases was used to identify relevant studies published between January 2000 and September 2024. The quality of each article was assessed using the Newcastle-Ottawa Scale (NOS) checklist. Data analysis was performed using STATA Ver. 11 software, and the standard error was calculated using the binomial distribution formula. The heterogeneity of the study results was assessed using the I-square and Q index, while publication bias was examined using the Begg’s test. In addition, a random effects model was used to determine the risk difference (RD), and a forest plot diagram was used to present the results with 95% confidence intervals. The Trim and Fill test was applied to estimate publication bias, and sensitivity analysis was performed to assess the influence of individual studies on the overall estimate. Results Of the nine studies, the relationship between BK virus (BKV) and the Merkel cell polyomavirus (MCV) and oral cancer was investigated. In five primary studies, and by combining the results of these studies, the risk of oral cancer in MCV and BKV-positive individuals was significantly higher than in the negative groups by 13% (RD: 0.13, 95% CI: 0.00, 0.26) and 2% (RD: 0.02, 95% CI: -0.03, 0.07), respectively. In addition, the association between JC virus (JCV) and oral cancer was investigated in six primary studies. By combining the results of these studies, the risk of oral cancer in JCV-positive individuals was 1% higher than that in JCV-negative individuals (RD: 0.01, 95% CI: -0.02, 0.06). Discussion This meta-analysis showed that there was a significant association between MCV and oral cancer, and the risk of oral cancer in MCV- positive individuals was 13% higher than that in MCV- negative individuals. More preliminary studies are needed on the association between BKV and JCV and the risk of oral cancer.

Infectious diseases are a significant burden in global healthcare. Pathogens engage with different host defense mechanisms. However, it is currently unknown if there are disease-specific immune signatures and/or if different pathogens elicit common immune-associated molecular entities to common therapeutic interventions. We studied patients enrolled through the Human Immunology Project Consortium (HIPC), which focuses on immune responses to various infections. Blood samples were collected and analyzed from patients during infection and follow-up time points at the convalescent stage. The study included samples from patients with Lyme disease (LD), tuberculosis (TB), malaria (MLA), dengue virus (DENV), and West Nile virus (WNV), as well as kidney transplant patients with cytomegalovirus (CMV) and polyomavirus (BKV) infections. Using an antibody-based assay, we quantified ~ 350 cell surface markers, cytokines, and chemokines involved in inflammation and immunity. Unique protein signatures were identified specific to the acute phase of infection irrespective of the pathogen type, with significant changes during convalescence. In addition, tumor necrosis factor receptor superfamily member 6 (TNR6), C-C Motif Chemokine Receptor 7 (CCR7), and C-C motif chemokine ligand-1 (CCL1) were increased in the acute and convalescent phases across all viral, bacterial, and protozoan compared to blood from healthy donors. Furthermore, despite the differences between pathogens, proteins were enriched in common biological pathways such as cell surface receptor signaling pathway and response to external stimulus. In conclusion, we demonstrated that irrespective of the pathogen type, there are common immunoregulatory and proinflammatory signals.

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.

Abstract Background Currently, few literature reports document cases of decoy cells in the urine of umbilical cord blood transplant patients. The majority of the literature indicates that decoy cells are frequently identified in the urine of kidney transplant recipients. Case presentation This case report describes a patient with Myelodysplastic Neoplasms featuring a complex karyotype who underwent umbilical cord blood transplantation. Postoperative urinary cytology revealed decoy cells, and subsequent BK virus nucleic acid testing was positive. However, the routine use of antiviral drugs by the physicians led to insufficient attention to the decoy cells and BK virus, culminating in hemorrhagic cystitis. Conclusions Urine cytology is a simple, intuitive, rapid, and cost-effective analytical method. The presence of decoy cells in the urine can serve as an indicator for infection screening and provide a clue for clinical doctors: Detection of decoy cells in urine should prompt a more vigorous antiviral response to mitigate the risk of complications like hemorrhagic cystitis.

Background: BK virus (BKV) is a member of the polyomavirus family. The determination of anti-BKV immunoglobulin G (IgG) antibody levels in kidney donors and recipients has been reported as a possible predictor of the risk of BK nephropathy. Allograft dysfunction is a significant risk factor. The main objective of this study was to address the high prevalence of renal failure due to BKV nephropathy in kidney transplant recipients. This investigation aims to determine whether donors and recipients of renal transplants had BKV IgG antibodies before transplantation. Methods: Blood samples were collected from 46 kidney transplant recipients and their corresponding 46 donors. An enzyme-linked immunosorbent assay was used to qualitatively analyze human BKV IgG. Results: Ninety-two participants, 46 kidney transplant donors, and 46 kidney transplant recipients, were analyzed. Pretransplantation anti-BKV antibody levels were higher in kidney transplant donors (73%) than in recipients (63%). Donors and recipients included in the study were grouped into seropositive and seronegative recipients, with the highest proportion of seropositive recipient-donor groups (48%) and the lowest percentages in the seronegative donor and seronegative recipient groups. Fifty-one percent of the participants were male and 49% were female. The age distribution of most subjects was >50 years old. Conclusion: BKV can cause kidney transplant rejection. Routine screening of transplant recipients and donors for BKV IgG seropositivity is recommended before renal transplantation. This can improve transplant outcomes and prevent rejection.

Abstract Aims This study aims to evaluate the presence of EBV, HCMV, and BKV genomic sequences in the plasma samples (active infection/viremia) of kidney transplant recipients suspected of rejection and to investigate host and risk factors related to the activation of these viruses in these patients. Methods In this cross-sectional single-center study, plasma samples were collected from 98 suspected kidney transplant rejection patients at Labafinejad Hospital, Tehran, Iran, between December 2022 and June 2023. Quantitative real-time PCR assays for HCMV, EBV, and BK were performed using GeneProof Real-time PCR kits. ROC curve analysis was used to determine the viral load cutoff point for each virus. Findings HCMV active viremia was detected in 18 (18.36%) recipients, EBV active viremia in 7 (7.14%), and BKV active viremia in 5 (5.10%). ROC results indicated viral load cutoff points of 778, 661, and 457 points for HCMV, EBV, and BKV, respectively. The duration of time after transplantation significantly differed between active viremia and no viremia groups (120.5 vs. 46 months, P = 0.014). In the BKV active viremia group, the increase in creatinine compared to baseline creatinine was significantly higher than in the no viremia group (2.7 vs. 0.8, P = 0.017). The odds ratio of HCMV active viremia in patients taking tacrolimus was 2.84 times higher, and the odds of HCMV active viremia in patients taking antithymocyte globulin was 3.01 times higher than in patients not taking these drugs. Conclusion Rapid and timely diagnosis of viral active infections in kidney transplant patients is crucial for effective disease management and implementation of appropriate treatment strategies. Identifying potential risk factors, including host and treatment-related factors that influence transplantation, can facilitate the development of suitable preventive strategies.

Background/Objectives: With kidney transplant immunosuppression, physicians must balance preventing rejection with minimizing infection and malignancy risks. Steroids have been a mainstay of these immunosuppression regimens since the early days of kidney transplantation, yet their risks remain debated. Our study looks at the clinical outcomes of patients undergoing early steroid withdrawal (ESW) vs. steroid continuous (SCI) maintenance immunosuppression in adult kidney transplant recipients. Methods: A retrospective case-control study, utilizing propensity score-matching, was performed using the US Collaborative Network Database within TriNetX to evaluate renal transplant outcomes at one year in first-time kidney transplant adult patients (>18 years old) who were prescribed an ESW regimen (no steroids after post-transplant day 7 with maintenance tacrolimus [tac] + mycophenolic acid [MMP]/mycophenolate mofetil [MMF]) vs. SCI (tac + MMF/MMP + prednisone). Cohorts were matched on demographics, comorbidities, previously described risk factors for rejection, and induction immunosuppression. Primary outcomes included viral infections, pyelonephritis, and sepsis. Secondary outcomes included renal transplant rejection, death-censored allograft failure (eGFR < 15 mL/min), patient mortality, delayed graft function, and diabetes mellitus. Results: A total of 2056 patients were in each cohort after matching (mean age: 50.7–51 years, 17.9–20.0% African American, 60–60.6% male.) The SCI cohort had a significantly higher cumulative incidence of composite viremia (18 vs. 28.1%, ESW vs. SCI, p < 0.01) driven by CMV, EBV, and BK virus. Post-transplant diabetes mellitus was significantly higher in the SCI cohort (3.21% vs. 5.49%, ESW vs. SCI, p < 0.01). Delayed graft function was also higher in the SCI cohort (19.55% vs. 22.79%, ESW vs. SCI, p < 0.01). Pyelonephritis (2.3 vs. 4.91%, ESW vs. SCI, p < 0.01) and sepsis (2.15 vs. 5.95%, ESW vs. SCI, p < 0.01) were higher in the SCI cohort. Rejection rates were similar between ESW and SCI (29 vs. 31%, ESW vs. SCI, p = 0.41). There were significantly higher incidences of graft failure (4.9 vs. 9.9%, ESW vs. SCI, p < 0.01) and mortality (0.8 vs. 2.1%, ESW vs. SCI, p < 0.01) in the SCI cohort. Conclusions: This well-matched case-control study suggests that ESW is associated with lower infectious outcomes, mortality, and graft failure without increasing rejection risk, supporting the potential benefits of ESW in kidney transplant patients. [ABSTRACT FROM AUTHOR]

Background: Currently, few literature reports document cases of decoy cells in the urine of umbilical cord blood transplant patients. The majority of the literature indicates that decoy cells are frequently identified in the urine of kidney transplant recipients. Case presentation: This case report describes a patient with Myelodysplastic Neoplasms featuring a complex karyotype who underwent umbilical cord blood transplantation. Postoperative urinary cytology revealed decoy cells, and subsequent BK virus nucleic acid testing was positive. However, the routine use of antiviral drugs by the physicians led to insufficient attention to the decoy cells and BK virus, culminating in hemorrhagic cystitis. Conclusions: Urine cytology is a simple, intuitive, rapid, and cost-effective analytical method. The presence of decoy cells in the urine can serve as an indicator for infection screening and provide a clue for clinical doctors: Detection of decoy cells in urine should prompt a more vigorous antiviral response to mitigate the risk of complications like hemorrhagic cystitis. [ABSTRACT FROM AUTHOR]

Background: BK-polyomavirus (BKpyV) nephropathy (BKVN) is associated with end-stage kidney disease in kidney and non-kidney solid organ transplantation, with no curative treatment. Case presentation: A 45-year-old woman with a past medical history of double lung transplantation subsequently developed end-stage kidney disease, of undetermined origin. One month after receiving a kidney transplant, a diagnosis of early BKVN was suspected, and in retrospect was a reasonable cause for the loss of her native kidneys. Minimisation of immunosuppression, achieved through extracorporeal photopheresis, allowed clearance of BKpyV and so prevented nephropathy. Both lung and kidney grafts had a satisfactory and stable function after one year of follow-up, with no rejection. Conclusions: Extracorporeal photopheresis may have facilitated minimisation of immunosuppression and BKpyV clearance without lung allograft rejection. [ABSTRACT FROM AUTHOR]

Background: Human Immunodeficiency Virus (HIV) and malaria are two major diseases in sub-Saharan Africa. Co-infection can significantly impact the clinical outcomes of both conditions. We assessed the proportion of HIV-infected children at Korle Bu Teaching Hospital (KBTH) and Princess Marie Louise Hospital (PML) with malaria parasites. The association between asymptomatic malaria parasitaemia and virological non-suppression was also determined in these children. Methods: This cross-sectional study of 277 asymptomatic malaria in children receiving care at paediatric HIV clinics at KBTH and PML was conducted from September to November 2022. Patients who had been on antiretroviral therapy (ART) for at least six months were eligible to participate. Structured questionnaires were used to collect socio-demographic information, malaria prevention behaviors, and ART-related data using in-person interviews. Microscopy and PCR were used to screen for malaria, and GeneXpert was used to determine viral load. To examine the determinants of malaria PCR positivity and virological non-suppression, chi-square tests and logistic regression were performed. Results: The median age of the participants was 9 years (range: 6–12 years). Males comprised 158 (57%) of the study population. We detected 10 (3.6%) and 21 (7.6%) malaria cases by microscopy and PCR, respectively. Virological non-suppression (VL > 1000 copies/ml) was observed in 82 (29.6%) of the 277 participants. Among the suppressed individuals, 62 (22.4%) exhibited low-level viraemia (VL level 40-1000 copies/ml) and 133 (48%) had undetectable viral load levels. No factors were associated with the presence of malaria PCR positivity carriage. Poor adherence to ART was associated with a five-fold increase in the risk of viral load non-suppression (AOR = 4.89 [CI = 2.00-11.98], p = 0.001). Conclusion: The proportion of children living with HIV with asymptomatic malaria parasitaemia was low. Approximately one-third of the study population had virological non-suppression. The interaction between malaria parasitemia and viral replication may not be the main cause for virological non-suppression in this low transmission area. [ABSTRACT FROM AUTHOR]

Aims: This study aims to evaluate the presence of EBV, HCMV, and BKV genomic sequences in the plasma samples (active infection/viremia) of kidney transplant recipients suspected of rejection and to investigate host and risk factors related to the activation of these viruses in these patients. Methods: In this cross-sectional single-center study, plasma samples were collected from 98 suspected kidney transplant rejection patients at Labafinejad Hospital, Tehran, Iran, between December 2022 and June 2023. Quantitative real-time PCR assays for HCMV, EBV, and BK were performed using GeneProof Real-time PCR kits. ROC curve analysis was used to determine the viral load cutoff point for each virus. Findings: HCMV active viremia was detected in 18 (18.36%) recipients, EBV active viremia in 7 (7.14%), and BKV active viremia in 5 (5.10%). ROC results indicated viral load cutoff points of 778, 661, and 457 points for HCMV, EBV, and BKV, respectively. The duration of time after transplantation significantly differed between active viremia and no viremia groups (120.5 vs. 46 months, P = 0.014). In the BKV active viremia group, the increase in creatinine compared to baseline creatinine was significantly higher than in the no viremia group (2.7 vs. 0.8, P = 0.017). The odds ratio of HCMV active viremia in patients taking tacrolimus was 2.84 times higher, and the odds of HCMV active viremia in patients taking antithymocyte globulin was 3.01 times higher than in patients not taking these drugs. Conclusion: Rapid and timely diagnosis of viral active infections in kidney transplant patients is crucial for effective disease management and implementation of appropriate treatment strategies. Identifying potential risk factors, including host and treatment-related factors that influence transplantation, can facilitate the development of suitable preventive strategies. [ABSTRACT FROM AUTHOR]

Posttransplantation complications pose a major challenge to the long‐term survival and quality of life of organ transplant recipients. These complications encompass immune‐mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft‐versus‐host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients. [ABSTRACT FROM AUTHOR]

Summary: Background: BK polyomavirus (BKV) DNAaemia occurs in 10% of recipients of kidney transplants, contributing to premature allograft failure. Evidence suggests disease is donor derived. Hypothetically, recipient infection with a different BKV serotype increases risk due to poorer immunological control. Thus, understanding the composition and activity of the humoral anti-BKV responses in donor/recipient (D/R) pairs is critical. Methods: Using 224 paired pre-transplant D/R samples, BKV VP1 genotype-specific pseudoviruses were employed to define the breadth of the antibody response against different serotypes (ELISA) and, to characterise specific neutralising activity (nAb) using the 50% inhibitory concentration (LogIC50). Mismatch (MM) ratios were calculated using the ratio of recipient ELISA or nAb reactive BKV serotypes relative to the number of donor reactive serotypes. Findings: BKV DNAaemia was observed in 28/224 recipients of kidney transplants. These recipients had lower nAb titres against all the serotypes, with median logIC50 values of 1.19–2.91, compared to non-viraemic recipients’ median logIC50 values of 2.13–3.30. nAb D/R MM ratios >0.67 associated with significantly higher risk of BKV viraemia, with an adjusted odds ratio of 5.12 (95% CI 2.07 to 13.04; p

The article discusses the validation of a model for noninvasive diagnosis of acute rejection in kidney transplant recipients using urinary chemokines CXCL9 and CXCL10. The study aimed to validate the model in an independent cohort of patients and found that the model slightly overestimated the risk of acute rejection, particularly in patients at higher risk. Despite this, the model showed good discriminatory capacity and may be useful for identifying patients at low risk of acute rejection who can safely avoid biopsies. The findings support the utility of this model in clinical decision-making for kidney transplant recipients. [Extracted from the article]

Introduction: JC-polyomavirus-associated nephropathy (JC-PVAN) is a rare cause of allograft dysfunction with only a few cases described in the literature. Case Presentation: We present 2 cases of JC-PVAN, both of which occurred >5 years after kidney transplantation. In both cases, transplant biopsies were performed because of worsening of kidney function. We found tubulitis and interstitial inflammation; immunohistochemistry was positive for SV40, but BK virus was not detected. The presence of JC virus confirmed the diagnosis of JC-PVAN. Immunosuppressive therapy was adopted, but in both cases graft function progressively deteriorated. Conclusions: Our cases show that JC-PVAN, although much rarer than BK-PVAN, should be considered a possible cause of graft dysfunction even years after transplantation. Complete diagnostic workup, including kidney biopsy, is crucial for correct diagnosis and treatment.

Polyomaviruses, particularly BK virus, are ubiquitous latent infections that may reactivate with immunosuppression during kidney transplantation, resulting in polyomavirus nephropathy (PVN). The levels of viruria and viremia serve as tools for screening and making a presumptive diagnosis of PVN, respectively, while a definitive diagnosis requires a kidney biopsy. There are histologic classifications of PVN based on the extent of tubular cell viral infection, interstitial fibrosis, and interstitial inflammation. These classifications correlate to some degree with graft function and loss, aiding in determining treatment efficacy and prognostication. PVN has histologic overlap with acute cell-mediated rejection, making the differential diagnosis challenging, although there are suggestive features for these different causes of graft dysfunction. This article reviews the diagnosis, histologic findings, and classifications of PVN, and discusses how to differentiate viral nephropathy from acute rejection.

A small percentage of bladder cancers in the general population have been found to harbor DNA viruses. In contrast, up to 25% of tumors of solid organ transplant recipients, who are at an increased risk of developing bladder cancer and have an overall poorer outcomes, harbor BK polyomavirus (BKPyV). To better understand the biology of the tumors and the mechanisms of carcinogenesis from potential oncoviruses, we performed whole genome and transcriptome sequencing on bladder cancer specimens from 43 transplant patients. Nearly half of the tumors from this patient population contained viral sequences. The most common were from BKPyV (N=9, 21%), JC polyomavirus (N=7, 16%), carcinogenic human papillomaviruses (N=3, 7%), and torque teno viruses (N=5, 12%). Immunohistochemistry revealed variable Large T antigen expression in BKPyV-positive tumors ranging from 100% positive staining of tumor tissue to less than 1%. In most cases of BKPyV-positive tumors, the viral genome appeared to be clonally integrated into the host chromosome consistent with microhomology-mediated end joining and coincided with focal amplifications of the tumor genome similar to other virus-mediated cancers. Significant changes in host gene expression consistent with the functions of BKPyV Large T antigen were also observed in these tumors. Lastly, we identified four mutation signatures in our cases, with those attributable to APOBEC3 and SBS5 being the most abundant. Mutation signatures associated with an antiviral drug, ganciclovir, and aristolochic acid, a nephrotoxic compound found in some herbal medicines, were also observed. The results suggest multiple pathways to carcinogenesis in solid organ transplant recipients with a large fraction being virus-associated.

Despite the high prevalence of BK polyomavirus (BKPyV) and the associated risk for BKPyV-associated nephropathy (BKPyVAN) in kidney transplant (KTX) recipients, many details on viral processes such as replication, maturation, assembly and virion release from host cells have not been fully elucidated. VP1 is a polyomavirus-specific protein that is expressed in the late phase of its replicative cycle with important functions in virion assembly and infectious particle release. This study investigated the localization and time-dependent changes in the distribution of VP1-positive viral particles and their association within the spectrum of differing cell morphologies that are observed in the urine of KTX patients upon active BKPyV infection. We found highly differing recognition patterns of two anti-VP1 antibodies with respect to intracellular and extracellular VP1 localization, pointing towards independent binding sites that were seemingly associated with differing stages of virion maturation. Cells originating from single clones were stably cultured out of the urine sediment of KTX recipients with suspected BKPyVAN. The cell morphology, polyploidy, virus replication and protein production were investigated by confocal microscopy using both a monoclonal (mAb 4942) and a polyclonal rabbit anti-VP1-specific antibody (RantiVP1 Ab). Immunoblotting was performed to investigate changes in the VP1 protein. Both antibodies visualized VP1 and the mAb 4942 recognized VP1 in cytoplasmic vesicles exhibiting idiomorphic sizes when released from the cells. In contrast, the polyclonal antibody detected VP1 within the nucleus and in cytoplasm in colocalization with the endoplasmic reticulum marker CNX. At the nuclear rim, VP1 was recognized by both antibodies. Immunoblotting revealed two smaller versions of VP1 in urinary decoy cell extracts, potentially from different translation start sites as evaluated by in silico analysis. Oxford Nanopore sequencing showed integration of BKPyV DNA in chromosomes 3, 4 and 7 in one of the five tested primary cell lines which produced high viral copies throughout four passages before transcending into senescence. The different staining with two VP1-specific antibodies emphasizes the modification of VP1 during the process of virus maturation and cellular exit. The integration of BKPyV into the human genome leads to high virus production; however, this alone does not transform the cell line into a permanently cycling and indefinitely replicating one. [ABSTRACT FROM AUTHOR]

A recent study published in Transplant International explores the use of stem cell-derived islet transplantation as a potential treatment for type 2 diabetes. The study details the successful transplantation of islet tissue derived from induced pluripotent stem cells into a patient with type 2 diabetes, which resulted in improved islet function. However, the study also acknowledges the need for more information on quality control and the limitations of diagnosing the patient's diabetes. The authors suggest that further research is necessary to fully understand the safety and effectiveness of this treatment. The document provides a summary of the study, including information on its focus, findings, and the authors' contributions and funding. [Extracted from the article]

This article examines the effectiveness of monoclonal antibodies (mAbs) in neutralizing SARS-CoV-2 variants in kidney transplant recipients. The study found that certain mAbs had low levels of neutralizing activity against specific variants, but in vivo neutralization showed slightly increased activity after administration. The article suggests that even though these variants are no longer circulating, there is still residual antiviral activity. The study also discusses the potential benefits of increasing the dosage of mAbs to enhance their efficacy against COVID-19 variants. However, the study has limitations, and further research is needed to better understand antibody activity and optimize patient care. Funding for the research was received from various sources, and some authors have declared potential conflicts of interest. [Extracted from the article]

Objective: To evaluate the efficacy and safety of hydroxychloroquine sulfate (HCQ) in the treatment of low risk phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN). Methods: A total of 110 patients with low risk PLA2R-associated MN were included in the study. Patients who met the inclusion and exclusion criteria were assigned randomly to two groups: the HCQ treatment group and the control group. The control group received standard supportive treatment according to the guidelines, while the HCQ treatment group received HCQ in addition to the supportive treatment. The clinical data of the patients were analyzed, with comparisons made at baseline and during the six-month follow-up period. Any adverse reactions were recorded. Results: The baseline data were comparable between the HCQ treatment group and the control group. At the end of the six-month follow-up period, the reductions in urine protein excretion and serum PLA2R antibody titer were more notable in the HCQ treatment group than those in the control group, with these differences being statistically significant (p < 0.05). Compared to the control group, the HCQ treatment group had fewer patients who were converted from low risk to moderate-to-high risk (p = 0.084). There were also no severe adverse reactions in the HCQ treatment group. Conclusion: In patients with low risk PLA2R-associated MN, adequate supportive therapy combined with HCQ is superior to supportive therapy alone in controlling proteinuria and reducing serum PLA2R antibody titers. Additionally, our study demonstrated that the incidence of adverse reactions did not increase. Trial registration: This study was registered in the Chinese Clinical Trial Registry (Registration No.: ChiCTR1900021757, Date of registration: 2019-03-08). [ABSTRACT FROM AUTHOR]

Introduction: Respiratory syncytial virus (RSV) can cause severe respiratory infections in adults; however, information on associated sequelae is limited. This systematic literature review aimed to identify sequelae in adults within 1 year following RSV-related hospitalization or resolution of acute infection. Methods: Studies were identified from Embase, MEDLINE, LILACS, SciELO, and grey literature. Random-effects meta-analyses using restricted maximum likelihood were used to calculate the proportions and relative risks of sequelae in patients with RSV compared with controls (patients with RSV-negative influenza-like illness, influenza, and parainfluenza) per follow-up period, population, and treatment setting, where possible. Results: Twenty-one relevant studies covering the period from 1990 to 2019 were included. Among the general population, the most frequent clinical sequela was sustained function loss (33.5% [95% CI 27.6–39.9]). Decline in lung function and cardiovascular event or congestive heart failure were also identified. Utilization sequelae were readmission (highest at > 6 months after discharge) and placement in a skilled nursing facility. The only subpopulation with data regarding sequelae was transplant patients. Among lung transplant patients, the most frequently reported clinical sequelae were decline in lung function, followed by graft dysfunction and bronchiolitis obliterans syndrome. Pooled relative risks were calculated for the following sequela with controls (primarily influenza-positive patients): cardiovascular event (general population) and pulmonary impairment (hematogenic-transplant patients) both 1.4 (95% CI 1.0–2.0) and for readmission (general population) 1.2 (95% CI 1.1–1.3). Conclusions: Although less data are available for RSV than for influenza or other lower respiratory tract infections, RSV infection among adults is associated with medically important sequelae, with a prevalence similar to other respiratory pathogens. RSV sequelae should be included in disease burden estimates. [ABSTRACT FROM AUTHOR]

Infection management in solid organ transplantation poses unique challenges, with a diverse array of potential pathogens and associated antimicrobial therapies. With limited high-quality randomized clinical trials to direct optimal care, therapeutic "myths" may propagate and contribute to suboptimal or excessive antimicrobial use. We discuss 6 therapeutic myths with particular relevance to solid organ transplantation and provide recommendations for infectious diseases clinicians involved in the care of this high-risk population. [ABSTRACT FROM AUTHOR]

Since the significance of viral infections in children and adolescents with nephrotic syndrome (NS) is yet to be defined, this study intended to estimate the occurrence, pattern, and outcomes of some DNA viral infections in children with NS. Methods: A prospective study was conducted to determine the genome identification of the viruses Epstein-Barr (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6 type A and type B) and 7 (HHV-7), polyomavirus (BKV), and human adenovirus (HAdV) in plasma and urine samples of pediatric patients with NS. Results: A total of 35 patients aged 1 to 18 years with NS and under immunosuppressant drugs participated in the study. Plasma and urine samples were collected at regular intervals during a median follow-up of 266 days (range 133–595), and DNA was analyzed to detect the selected DNA viruses. Eleven patients (31.4%) had active virus infections, and patterns were classified as coinfection, recurrent, and consecutive. Of these, six patients (54.5%) presented viral coinfection, six (54.5%) viral recurrence, and seven patients (63.3%) had viral consecutive infection. Ten of the eleven patients with active infection had a proteinuria relapse (91%) and eight (72.7%) were hospitalized (p = 0.0022). Active HCMV infection was the most frequent infection and was observed in six patients (54.5%), three of the eleven patients (27.2%) had suspected HCMV disease in the gastrointestinal tract, and one had HHV-7 coinfection. The frequency of other infections was: 9% for HHV-6, 45.5% for BKV, 27.3% for HHV-7, 18.2% for EBV, and 18.2% for HAdV. Conclusion: viral infections, especially HCMV, can be an important cause of morbidity and nephrotic syndrome relapse in children. [ABSTRACT FROM AUTHOR]

Background: Polyomavirus BK is one of the life-threatening infections in kidney transplant recipients. The activation of this virus can eventually lead to the loss of the graft. There are very few studies on the expression level of BK virus microRNAs. Therefore, in this study, we investigated the function of BK virus microRNAs and their effect on host cell microRNAs’ expression level. BK virus encodes two microRNAs, namely miR-B1-3p and miR-B1-5p. Therefore, it is crucial to study these microRNAs as markers of viral infection and their regulation. So far, there is no approved drug or vaccine to treat BK virus infection. Consequently, understanding the relationship between BK virus and host cell microRNAs is integral to the control of infection in kidney transplant patients. Materials and Methods: In this study, ten tissue samples from kidney transplant recipients with symptoms of BK virus nephropathy, ten urine samples from kidney transplant patients without active BK virus infection, and 20 healthy individuals were included. The expression level of the studied microRNAs was measured in all the samples using SYBR Green Real-time PCR. Results: The results showed that the expression level of the studied microRNAs, including miR-B1-3p, miR-B1-5p, miR-155, miR-520, miR-10b, miR-30a in the tissue samples of kidney transplant patients with BK virus nephropathy symptoms were significantly increased compared to kidney transplant patients without active BK virus infection. Conclusion: The assessment of some microRNAs, such as miR-520, miR-30a, and miR-B1-3p/5p, may assist in the prediction and prevention of BKPyV activation in KTRs, particularly in urine samples.

The article "A Hitchhiker's Guide to the BK Galaxy" published in Transplant International discusses the challenges posed by the BK polyomavirus in kidney transplant patients. It highlights the importance of following the Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation. The article suggests a lean approach to implementing the guidelines, focusing on an infographic, conceptual timeline, and flowchart for clinical translation. It emphasizes the need for a multidisciplinary team approach to harmonize and successfully implement the guidelines, with a focus on reducing immunosuppression guided by plasma BK polyomavirus DNA load. The article also identifies areas of uncertainty and the need for further research to improve outcomes for kidney transplant recipients. [Extracted from the article]

The article "Current Challenges and Advances on Infectious Diseases in Solid Organ Transplantation" discusses the impact of infections on solid-organ transplant recipients, highlighting the role of immunosuppressive drugs and surgical procedures in shaping infection epidemiology. Various topics such as managing infections, antibiotic approaches, and innovative strategies like fecal transplantation are covered. The article also delves into specific infections like cytomegalovirus and multidrug-resistant organisms, emphasizing the need for advanced diagnostics and access to new antibiotics to improve outcomes in transplant recipients. Overall, the article provides a comprehensive overview of transplant infectious diseases and underscores the importance of multidisciplinary management strategies for better patient outcomes. [Extracted from the article]

The article "Transplant Trial Watch" discusses a study on heart transplant recipients comparing outcomes of everolimus versus a standard regimen. The study followed participants for 12 years and found a significant benefit in renal function for the everolimus group. Another study in the article focuses on a novel monoclonal antibody, MAU868, targeting BK polyomavirus VP1, showing promising results in safety and tolerability. These studies offer potential advancements in heart transplantation and BK virus treatment, respectively. [Extracted from the article]

Background: Notice to the importance of BK virus infection in kidney transplant patients, the present study aimed to present a protocol related to design aspects and implement a registration system for kidney transplant patients with BK virus infection in Isfahan Province, Iran. Method: The design process and different aspects of implementation and preparation of the platform for the registration of kidney transplant patients with BK virus infection were presented in this study. Indices related to the diagnosis, monitoring of the course of the disease, and the most important criteria related to the disease caused by BK virus and treatment of BK virus infection in kidney transplant patients were searched in reliable scientific databases such as PubMed, Scopus, Up-To-Date, ScienceDirect, and Web of Science. A team consisting of experts in nephrology, biostatistics, and epidemiology evaluated the specified variables as an expert panel and evaluated the content validity of the checklists designed quantitatively and qualitatively to finalize them. Results: The checklist was finalized in three sections: 1) demographic variables (age, gender, education,…), 2) clinical variables (primary cause of kidney failure, disease history, history of kidney disease in the family, laboratory and diagnostic parameters, clinical manifestations…), and 3) microbiologic information of BK virus infection. This information can be used for the diagnosis, treatment, and follow-up of the patient. Conclusions: Our registry for kidney transplant patients with BK virus infection among the few ones in the world can provide a comprehensive valuable information collection about the risk factors and the course of changes in various indices in these patients and may improve the treatment process.

BK viremia (BKPyV-DNAemia) and nephropathy (BKPyVAN) are significant causes of morbidity and mortality in kidney transplant recipients (KTRs). Vitamin D supports immune function, yet low 25-hydroxyvitamin D [25(OH)D] is common among KTRs. The association between serum 25(OH)D, measured 61 days to 2 years post-transplant, and subsequent incident BKPyV-DNAemia and BKPyVAN was examined in KTRs without previous BKPyV-DNAemia or BKPyVAN, respectively. Out of 3308 KTRs, 399 (12%) were vitamin D deficient [25(OH)D ≤ 20 ng/mL], and 916 (27.7%) were insufficient [25(OH)D 21–29 ng/mL]. A total of 184 KTRs developed BKPyV-DNAemia and 44 developed BKPyVAN. The incidence rate (/100 person-years) for BKPyV-DNAemia was 2.88 in the 25(OH)D sufficient group, 2.22 in the insufficient group, and 2.37 in the deficient group. The incidence rate (/100 person-years) for BKPyVAN was 0.30 in the 25(OH)D sufficient group, 0.75 in the insufficient group, and 1.28 in the deficient group. Vitamin D deficiency (adjusted hazard ratio [aHR] compared to 25(OH)D sufficiency: 3.92; 95% CI: 1.66–9.23) and insufficiency (aHR: 2.22; 95% CI: 1.11–4.45) remained significantly associated with the incidence of BKPyVAN after adjustment for baseline characteristics. Low serum 25(OH)D was associated with an increased risk of BKPyVAN but not BKPyV-DNAemia.

This article discusses the use of immune repertoire sequencing as a non-invasive and precise diagnostic method for kidney transplant rejection. The study enrolled 10 recipients with ambiguous diagnoses of transplant kidney dysfunction and used immune repertoire sequencing to classify patients into rejection and non-rejection categories. The sequencing results largely matched biopsy pathological results, with major clone expansions corresponding to rejection types. The study also demonstrated the potential of immune repertoire sequencing in monitoring treatment effectiveness and diagnosing refractory rejection. However, further research is needed to analyze patterns in immune repertoire changes associated with viral infections or calcineurin inhibitors toxicity. [Extracted from the article]

Introduction. 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. Methods. 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. Results. 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). Conclusion. 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. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Non‐lupus full house nephropathy is a rare entity that is still poorly understood. It can complicate post‐transplant kidneys and result in a de novo process. Treatment is difficult but can be possibly achieved with optimization of immune suppression. Non‐lupus full house nephropathy is a rare entity with an unclear incidence. It describes the kidney biopsy findings of positive deposits for IgG, IgA, IgM, C3, and C1q on immunofluorescence in the absence of the classical diagnostic features of systemic lupus nephritis. This disease entity is becoming more recognized but further studies are still needed to evaluate the incidence, etiologies, and management of this condition. Transplant glomerulopathy is a major cause for renal graft loss. It can present with a wide variety of manifestations; it can cause AKI, CKD, or glomerular inflammations through an immune complex or autoimmune‐mediated damage. [ABSTRACT FROM AUTHOR]

Purpose: The assessment of tear film and ocular surface conditions in patients with acquired immunodeficiency syndrome (AIDS) has been poorly studied thus far. We aim to assess tear film parameters, ocular surface characteristics, and dry eye disease (DED) symptoms of patients with AIDS who did not undergo highly active antiretroviral treatment (HAART). Methods: This case-control study included 154 age-, sex-, and ethnicity-matched healthy controls and patients with AIDS. All participants underwent comprehensive ocular surface assessment and subjective DED symptomology evaluation. Data were collected between March 2022 and July 2022. Results: HAART-naïve patients with AIDS had a shorter noninvasive tear film breakup time (median 3.76 vs. 8.54 s), thinner tear film lipid layer thickness (median 73.00 vs. 91.00 nm), and lower Schirmer I test values (median 5.00 mm/5 min vs. 12.00 mm/5 min) (all P < 0.001). Moreover, higher corneal fluorescein staining scores (median 1.00 vs. 0.00) and higher upper, lower, and total meibomian gland grades were observed in AIDS patients (all P < 0.05). Negative correlations between the blood viral load and the Ocular Surface Disease Index score (r = -3.50, P = 0.027) and the Schirmer I test score (r = -0.374, P = 0.017) were detected in patients with AIDS. Conclusion: Altered tear film status was observed in individuals with HAART-naïve AIDS, even when there were no other ocular symptoms present. Therefore, patients with AIDS should be encouraged to undergo comprehensive ocular surface examinations to detect any subclinical tear film alterations occurring. [ABSTRACT FROM AUTHOR]