scholarly journals Innate Immunity Response to BK Virus Infection in Polyomavirus-Associated Nephropathy in Kidney Transplant Recipients

2022 ◽  
Vol 3 (1) ◽  
pp. 20-32
Author(s):  
Wiwat Chancharoenthana ◽  
Asada Leelahavanichkul
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Kidney Transplantation ◽  
Hemorrhagic Cystitis ◽  
Graft Loss ◽  
Clinical Manifestations ◽  
Bk Virus ◽  
Kidney Transplant Recipients ◽  
Wide Range ◽  
Novel Strategy

BK polyomavirus (BKV) mainly causes infection in uroepithelial and renal tubular epithelial cells of either immunocompetent or immunocompromised hosts. Despite asymptomatic or mild clinical features in immunocompetent hosts with BK infection, serious complications are frequently found in immunocompromised patients, especially patients with kidney transplantation. Accordingly, BKV-associated nephropathy (BKVN) demonstrates a wide range of clinical manifestations, including ureteric stenosis and hemorrhagic cystitis. In addition, BKV re-infection in post-kidney transplantation is also a main cause of kidney allograft dysfunction and graft loss. Since the direct anti-BKV is unavailable, immune response against BKV infection is the main mechanism for organism control and might be a novel strategy to treat or suppress BKV. As such, the innate immunity, consisting of immune cells and soluble molecules, does not only suppress BKV but also enhances the subsequent adaptive immunity to eradicate the virus. Furthermore, the re-activation of BKV in BKVN of kidney-transplanted recipients seems to be related to the status of innate immunity. Therefore, this review aims to collate the most recent knowledge of innate immune response against BKV and the association between the innate immunity status of kidney-transplanted recipients and BKV re-activation.

scholarly journals Survey of BK Virus in Renal Transplant Recipients in Iran: A Systematic Review and Meta-Analysis

Intervirology ◽  
2020 ◽  
pp. 1-9
Author(s):  
Somayeh Shatizadeh Malekshahi ◽  
Hoorieh Soleimanjahi ◽  
Fariba Dorostkar ◽  
Vahid Salimi ◽  
Mohammad Farahmand
Keyword(s):  
Renal Transplant ◽  
Meta Analysis ◽  
Hemorrhagic Cystitis ◽  
Random Effect ◽  
Graft Loss ◽  
Epidemiological Studies ◽  
Bk Virus ◽  
Iranian Population ◽  
Renal Transplant Recipients ◽  
Plasma Samples

<b><i>Introduction:</i></b> BK virus (BKV) infection in renal transplant (RT) recipients can cause hemorrhagic cystitis, transient renal dysfunction, and BKV nephropathy (BKVN). The prevalence and significance of BKV in RT recipients remain to be clarified in the Iranian population. The purpose of this review is to summarize the overall prevalence of BKV infection in RT recipients from previously published studies in Iran. <b><i>Methods:</i></b> We systematically reviewed articles through a comprehensive search of the main electronic and Persian national databases up to November 2019. <b><i>Results:</i></b> The overall pooled prevalence of BKV infection among the Iranian population was 23% (95% CI; 15–33%). Comparing these studies revealed that the prevalence of BKV in plasma samples ranges from 3 to 40%, in renal biopsies 1–13%, and in urine samples 10–49%. Due to substantial heterogeneity among reported studies (<i>I</i><sup>2</sup> = 93%, <i>p</i> &#x3c; 0.01), random-effect meta-analysis was performed. BKV infection rate was slightly higher in women than men (16%, <i>p</i> = 0.04 vs. 14%, <i>p</i> &#x3c; 0.01, respectively). The majority of the studies employed real-time PCR (24%, <i>I</i><sup>2</sup> = 93, <i>p</i> &#x3c; 0.01) and analyzed plasma samples alone or in combination with other types of specimens. BKV prevalence from 5 cities among the Iranian population showed a higher prevalence rate in Guilan. <b><i>Conclusion:</i></b> Our analysis provides a preliminary estimate of the epidemiology of BKV infection in RT recipients in Iran. These results arouse a need for more epidemiological studies of BKV infection in different unanalyzed regions in Iran. Early detection of BKV in RT recipients helps timely nephropathy diagnosis and prevents graft loss.

scholarly journals The EKiTE network (epidemiology in kidney transplantation - a European validated database): an initiative epidemiological and translational European collaborative research

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
M. Lorent ◽  
◽  
Y. Foucher ◽  
K. Kerleau ◽  
S. Brouard ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Clinical Epidemiology ◽  
Main Body ◽  
Large Set ◽  
Kidney Transplant Recipients ◽  
Clinical Practices ◽  
Post Transplantation ◽  
Wide Range ◽  
Epidemiology Studies ◽  
Transplantation Outcomes

Abstract Background Kidney transplantation is considered to be the treatment of choice for people with end-stage renal disease (ESRD). However, due to the shortage of available organs and the increase in the ESRD prevalence in Europe, it is essential to improve transplantation outcomes by studying the related prognostic factors. Today, there is no European registry collecting data to perform such clinical epidemiology studies. Main body Entitled EKiTE, for European cohort for Kidney Transplantation Epidemiology, this prospective and multicentric cohort includes patients from Spanish (Barcelona), Belgian (Leuven), Norwegian (Oslo) and French (Paris Necker, Lyon, Nantes, Nancy, Montpellier, Nice and Paris Saint Louis) transplantation centers and currently contains 13,394 adult recipients of kidney (only) transplantation from 2005 and updated annually. A large set of parameters collected from transplantation until graft failure or death with numbers of post-transplantation outcomes. The long-term follow-up and the collected data enable a wide range of possible survival and longitudinal analyses. Conclusion EKiTE is a multicentric cohort aiming to better assess the natural history of the ESRD in European kidney transplant recipients and perform benchmarking of clinical practices. The data are available for clinical epidemiology studies and open for external investigators upon request to the scientific council. Short-term perspectives are to extend EKITE network to other European countries and collect additional parameters in respect of the common thesaurus.

scholarly journals 2658. Meningitis in Kidney Transplant Recipients: TransMéninges, a French Multicentric Retrospective Cohort Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S930-S930
Author(s):  
Yanis Tamzali ◽  
Anne Scemla ◽  
Pierre Taupin ◽  
Sunny Randhawa ◽  
Valérie Moal ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Immunosuppressive Treatment ◽  
Induction Treatment ◽  
High Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Specific Population ◽  
Gram Negative ◽  
Wide Range

Abstract Background The management of meningitis requires the prompt introduction of high-dose probabilistic anti-infectious therapy. The literature reporting on meningitis in kidney transplant recipients (KTR) is scarce and no recommendation exists for this specific population. Methods We retrospectively included all adult KTRs diagnosed with meningitis (cerebro-spinal fluid (CSF) cell count >10/mm3 or positive fungal antigen or direct examination) between 2007 and 2018 in 16 French hospitals. Clinical, biological, and therapeutic data, and 1-year kidney and patient survival were collected. Results Meningitis occurred in 134 KTRs (mean age 57+/11.8 years, 56% male), after a median time of 27 months (IQR 8–65); 25% of patients received an immunosuppressive treatment before kidney transplantation, induction treatment included lymphocyte-depleting antibodies in 63%, and 53% presented diabetes (34% before and 19% after the transplantation). The etiologies included Cryptococcus neoformans (30%), Herpesviridae (22%, including Varicella-Zoster Virus 15%), idiopathic forms (11%), Gram-negative bacilli (8% of which 20% produced an extended spectrum β-lactamase), %), infusion of intravenous immunoglobulins (6%), post-transplant lymphoproliferative disorders (5%), Aspergillus fumigatus (4%), Listeria monocytogenes (4%), Enterovirus (4%), and Mycobacterium tuberculosis (3%). The most common symptoms were fever (82.5%), headaches (75%), encephalitis (55%), and convulsion (22.5%). CSF hypercellularity (found in 92% of the cases) was lymphocytic in 65% of the cases and neutrophilic in 35%. Initial anti-infectious therapy was inappropriate in 27% of the cases. One-year patient, graft, and death-censored graft survival rates were 84%, 76%, and 89%, respectively. Conclusion Meningitis after kidney transplantation encompasses a wide range of causes, with C. neoformans and VZV explaining more than 50% of the cases. Gram-negative bacilli are the most represented bacteria with a high rate of antimicrobial resistance. Treatment guidelines should be reconsidered in the specific population of KTRs as the etiology greatly differs from what is observed in the general population. Disclosures All authors: No reported disclosures.

scholarly journals P1706THE GRAFT SURVIVAL OF KIDNEY TRANSPLANTATION ACCORDING TO ETHNICITY IN KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yeonsoon Jung ◽  
Jisu Kim ◽  
Haesu Jeon ◽  
Ye Na Kim ◽  
Ho Sik Shin ◽  
...  
Keyword(s):  
African American ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Cox Regression ◽  
Patient Survival ◽  
Graft Loss ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Data Set

Abstract Background African American kidney transplant recipients experience disproportionately high rates of graft loss. The aim of this analysis was to use a UNOS data set that contains detailed baseline and longitudinal clinical data to establish and quantify the impact of the current overall graft loss definition on suppressing the true disparity magnitude in US AA kidney transplant outcomes. Methods Longitudinal cohort study of kidney transplant recipients using a data set created by United Network for Organ Sharing (UNOS), including 266,128 (African American 70,215, Non-African American 195,913) transplant patient between 1987 and December 2016. Multivariable analysis was conducted using 2-stage joint modeling of random and fixed effects of longitudinal data (linear mixed model) with time to event outcomes (Cox regression). Results 195,913 non-African American (AA) (73.6%) were compared with 70,215 AA (26.4%) recipients. 10-year-graft survival of AA in all era is lower than that of non-AA (31% in deceased kidney transplants (DKT) AA recipient and 42% in living kidney transplantation (LKT) non-AA recipient). 10-year-patient survival of AA with functioning graft in all era is similar that of non-AA. Multivariate Cox regression of factors associated with patient survival with functioning graft are acute rejection within 6 months, DM, hypertension and etc. Pre-transplant recipient BMI in AA show the trend as a protective factor in patient survival with functioning graft although not significantly in statistics Conclusions African American kidney transplant recipients experience a substantial disparity in graft loss, but not patient death with functioning graft.

scholarly journals PATTERN-RECOGNIZING RECEPTORS AND THE INNATE IMMUNE RESPONSE TO VIRAL INFECTION

2018 ◽  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Viral Infection ◽  
Innate Immune Response ◽  
English Literature ◽  
Innate Immune ◽  
Viral Pathogens ◽  
Antiviral Immune Response ◽  
Viral Antigens ◽  
Wide Range

The innate immune response to viral pathogens is crucial in mobilizing defensive reactions of an organism during the development of an acute viral infection. Cells of the innate immunity system detect viral antigens due to genetically programmed pattern-recognition receptors (PRRs), which are located either on the cell surface or inside the certain intracellular components. These image-recognizing receptors include Toll-like receptors (TLRs), retinoic acid-inducible gene I-like receptors (RIG-I-like receptors), nucleotide oligomerization domain-like receptors (NOD-like receptors), also known as NACHT, LRR and PYD domains of the protein, and cytosolic DNA sensors. The trigger mechanisms for these receptors are viral proteins, and nucleic acids serve as activators. The presence of PRRs that are responsible for the determination of viral antigens in cellular components allows the cells of innate immunity to recognize a wide range of viral agents that replicate in various cellular structures, and develop an immune response to them. This article summarizes the disparate data presented in modern English literature on the role of PRRs and the associated signaling pathways. Understanding the recognition of viral pathogens required triggering a cascade of cytokine and interferon production provides insights into how viruses activate the signal paths of PRRs and the effect of the interaction of viral antigens and these receptors on the formation of the antiviral immune response.

scholarly journals Recurrence of FSGS after Kidney Transplantation in Adults

2020 ◽  
Vol 15 (2) ◽  
pp. 247-256 ◽  
Author(s):  
Audrey Uffing ◽  
Maria José Pérez-Sáez ◽  
Marilda Mazzali ◽  
Roberto C. Manfro ◽  
Andrea Carla Bauer ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Loss ◽  
Small Sample ◽  
Glomerular Disease ◽  
Response To Treatment ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Native Kidney

Background and objectivesFSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients.Design, setting, participants, & measurementsThe Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors.ResultsAmong 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0–8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival.ConclusionsIdiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.

scholarly journals BK Virus RNA in Renal Allograft Biopsies

2020 ◽  
Vol 68 (5) ◽  
pp. 319-325 ◽  
Author(s):  
Francesca Costigliolo ◽  
Kara Lombardo ◽  
Lois J. Arend ◽  
Avi Z. Rosenberg ◽  
Andres Matoso ◽  
...  
Keyword(s):  
Renal Allograft ◽  
Jc Virus ◽  
Graft Loss ◽  
T Antigen ◽  
Bk Virus ◽  
Kidney Transplant Recipients ◽  
Sv40 Large T Antigen ◽  
Virus Rna ◽  
Allograft Biopsy ◽  
Alternative Test

BK polyomavirus–associated nephropathy (BKpyVAN) remains a cause of graft loss in kidney transplant recipients on immunosuppressive therapy. Its diagnosis relies on the identification of BK virus (BKV) in the renal allograft biopsy by positive immunohistochemical (IHC) stain for the viral SV40 large T antigen, although in situ hybridization (ISH) for viral DNA is used in some centers. We examined tissue detection of BKV RNA by RNAscope, a novel, automated ISH test, in 61 allograft biopsies from 56 patients with BKpyVAN. We found good correlation between the estimate of BKV tissue load by RNAscope ISH and SV40 IHC ( R2 = 0.65, p<0.0001). RNAscope ISH showed 88% sensitivity and 79% specificity and, as an alternative test, could confirm the presence of BKV tissue in presumed BKpyVAN and rule out BKV as the causative agent in JC virus nephropathy. We also used tissue BK viral load estimates by both RNAscope ISH and SV40 IHC to examine the relation between tissue and plasma BK levels and found significant correlation only between BK viremia and tissue BK measured by RNAscope ISH. Our findings suggest that the RNAscope ISH assay could be a reliable test for BKV detection in allograft biopsies.

BK virus: microbiology, epidemiology, pathogenesis, clinical manifestations and treatment

2010 ◽  
Vol 4 (1) ◽  
pp. 3-18 ◽  
Author(s):  
Chakrapol Sriaroon ◽  
John N. Greene ◽  
Albert L. Vincent ◽  
Veronica T. Tucci ◽  
Mohamed A. Kharfan-Dabaja ◽  
...  
Keyword(s):  
Virus Infection ◽  
Treatment Guidelines ◽  
Current Knowledge ◽  
Virus Disease ◽  
Hemorrhagic Cystitis ◽  
Clinical Manifestations ◽  
Bk Virus ◽  
Molecular Diagnostic ◽  
Sufficient Information ◽  
Life Threatening

Abstract Background: BK virus infection is common but is usually asymptomatic. However, it can become life threatening as severe hemorrhagic cystitis (HC) or the polyomavirus-associated nephropathy (PVAN) particularly in immune compromised and transplant recipients. Some investigators have studied the pathophysiology and there are anecdotal and uncontrolled studies of therapy with few conclusions allowing treatment guidelines. Objectives: Summarize literature review of current knowledge concerning the nature, epidemiology, pathophysiology, diagnosis and treatment of this common virus infection. Results: HC is a not uncommon and often misdiagnosed infection from BK virus. It is usually self limited but can become life threatening in immune compromised patients. PVAN threatens survival of transplanted kidneys and is difficult to differentiate from rejection without sophisticated molecular diagnostic technology. We have sufficient information for making a diagnosis of BK virus disease by using clinical, serological and molecular technology. Studies using manipulation of immunosuppression and a variety of antiviral agents, including cidofovir, leflunomide, intravenous immunoglobulin, vidarabine, fluroquinolones, have been published but most were uncontrolled reports of few cases. Cidofovir offers some promise but more must be learned before there is hope for evidence-based treatment guidelines.

scholarly journals Recurrence of immunoglobulin A nephropathy after kidney transplantation: a narrative review of the incidence, risk factors, pathophysiology and management of immunosuppressive therapy

2020 ◽  
Vol 13 (5) ◽  
pp. 758-767
Author(s):  
Barbara Infante ◽  
Michele Rossini ◽  
Adelaide Di Lorenzo ◽  
Nicola Coviello ◽  
Castellano Giuseppe ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Renal Disease ◽  
Immunosuppressive Treatment ◽  
Graft Loss ◽  
Immunoglobulin A ◽  
Supportive Therapy ◽  
Kidney Graft ◽  
Immunoglobulin A Nephropathy ◽  
Kidney Transplant Recipients ◽  
End Stage

Abstract Glomerulonephritis (GN) is the underlying cause of end-stage renal failure in 30–50% of kidney transplant recipients. It represents the primary cause of end-stage renal disease for 25% of the dialysis population and 45% of the transplant population. For patients with GN requiring renal replacement therapy, kidney transplantation is associated with superior outcomes compared with dialysis. Recurrent GN was previously considered to be a minor contributor to graft loss, but with the prolongation of graft survival, the effect of recurrent disease on graft outcome assumes increasing importance. Thus the extent of recurrence of original kidney disease after kidney transplantation has been underestimated for several reasons. This review aims to provide updated knowledge on one particular recurrent renal disease after kidney transplantation, immunoglobulin A nephropathy (IgAN). IgAN is one of the most common GNs worldwide. The pathogenesis of IgAN is complex and remains incompletely understood. Evidence to date is most supportive of a several hit hypothesis. Biopsy is mandatory not only to diagnose the disease in the native kidney, but also to identify and characterize graft recurrence of IgAN in the kidney graft. The optimal therapy for IgAN recurrence in the renal graft is unknown. Supportive therapy aiming to reduce proteinuria and control hypertension is the mainstream, with corticosteroids and immunosuppressive treatment tailored for certain subgroups of patients experiencing a rapidly progressive course of the disease with active lesions on renal biopsy and considering safety issues related to infectious complications.

P1776HLA TYPING BY NGS ENHANCES MISMATCH DETECTION IN LIVING KIDNEY TRANSPLANTATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sarah Pehnke ◽  
Tom H Lindner ◽  
Bernt Popp ◽  
Ilias Doxiadis ◽  
Ramona Landgraf ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Loss ◽  
Hla Typing ◽  
University Hospital ◽  
Kidney Transplant Recipients ◽  
Antibody Mediated Rejection ◽  
Typing Methods ◽  
Long Range Pcr ◽  
Hla Mismatches

Abstract Background and Aims Antibody mediated rejection (ABMR) due to the development of donor specific HLA antibodies is the most common cause for graft loss in kidney transplant recipients. Therefore, a low count of HLA mismatches is favorable in the course of transplantation. Hitherto, several techniques for HLA typing have been adapted in parallel, e.g. serological or low-resolution PCR. In this single-center study, we aimed to perform “HLA re-typing” by next generation sequencing (NGS) in a living kidney transplant cohort (n=143), in order to identify HLA mismatches in donor/recipient pairs, that were missed by previous HLA typing methods. Method We isolated DNA of 102 donor/recipient pairs, that received a living kidney transplantation at the University Hospital Leipzig (Germany) between 1998 and 2018, and performed long range PCR of all known HLA loci. Using these NGS results, we compiled a genomic HLA mismatch formula. We evaluated, if genomic HLA typing identifies more HLA mismatches compared to the results of previous HLA typing methods, that were recorded in the Eurotransplant database for our donor/recipient pairs. Results By genomic HLA typing, we were able to identify HLA mismatches in 10.2 % of donor/recipient pairs, that have been missed by previous methods. In our cohort, we recognized most mismatches in the DRB1 locus, that were missed with other HLA typing techniques. Conclusion Our results suggest, that genomic HLA typing can be more precise in detecting HLA mismatches in donor recipient/pairs. Especially in the course of living kidney transplantation, a higher accuracy in HLA typing might enhance donor selection. Furthermore, accurate HLA typing can influence graft management in the course of ABMR, as it may improve the detection of donor specific HLA directed antibodies.

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