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BK-virus nephropathy in renal transplants—tubular necrosis, MHC-class II expression and rejection in a puzzling game

Published on Mar 1, 2000in Nephrology Dialysis Transplantation4.20
· DOI :10.1093/ndt/15.3.324
Volker Nickeleit11
Estimated H-index: 11
,
Hans H. Hirsch60
Estimated H-index: 60
(University of Basel)
+ 4 AuthorsMichael J. Mihatsch71
Estimated H-index: 71
(University of Basel)
Cite
Abstract
We review BK-virus nephropathy (BKN ) as Introduction a new complication that increasingly aVects renal allo- grafts and causes dysfunction. Since starting in 1996, Manifest polyomavirus infection of renal allografts we have seen 11 cases. Currently, the prevalence of with the BK-virus strain, i.e. BK-virus nephropathy BKN is 3% in our graft biopsies. The diagnosis can (BKN ), is an unusual complication that has recently only be made histologically. The virus aVects tubular been described (1-3). BKN causes severe graft dysfunc- epithelial cells that show characteristic intranuclear tion and contributes to graft loss (3-5). inclusion bodies. The major reason for impaired graft Polyomavirus (PV ), a subgroup of the papovavirus function and a possible way for viral particles to gain family, is a double stranded non-enveloped DNA virus access to the blood via peritubular capillaries is necrosis (6 ). Primary infection usually occurs early in life of infected epithelial cells. BK-virus DNA in the without clinical symptoms (6 ). PV frequently remains plasma, which can be detected by PCR, is closely in a dormant state in the kidneys and ureters of healthy, associated with nephropathy. BK-virus does not stimu- immunocompetent individuals (7-9). Immuno- late tubular MHC-class II expression as judged by compromised patients, however, have an increased immunofluorescence double labelling. The inflamma- risk of developing clinically manifest PV infection. tory response is inconsistent and the frequency of Human disease can be caused by two PV strains: JC rejection episodes is not increased during disease. and BK. JC-virus causes progressive multifocal leuko- Clinical manifestation of viral nephropathy evolves in encephalopathy (6,10). BK-virus is associated with several stages. (i) Initial, asymptomatic and reversible changes in the kidney (2,11) and, as proposed by some activation of the virus, judged by the presence of authors, with haemorrhagic cystitis and ureteral sten- inclusion bearing cells in the urine. (ii) High dose osis (12,13). Although immunosuppression increases immunosuppressive drug regimens, often including tac- the probability of latent BK-virus reactivation, clinical rolimus. (iii) Tubular injury and viraemia as additional manifestation of disease is rare. promoting conditions. BKN nephropathy was associ- In Basel we did not diagnose a single case of BKN ated with graft loss in 45% of our patients. The before 1996, even during previous high-dose cyclospo- remaining patients with persistent viral nephropathy rin therapy protocols (personal observation). However, showed renal dysfunction (serum creatinine levels on 10 patients with a total of 23 tissue samples were average 150% above baseline readings). Currently, no encountered in the following 3 years (current preval- established antiviral therapy is available. We discuss ence in transplant biopsies 3.1%, current prevalence in attempts to lower immunosuppression as a means to transplant recipients 4.5%). The prevalence in our control viral replication. We propose a diagnostic centre is similar to that recently reported by algorithm for screening and monitoring the disease. Drachenberg et al. (4). In comparison, a manifest CMV infection had been diagnosed in only 11 patients with a total of 16 graft biopsies over the past 32 years
  • References (23)
  • Citations (268)
Cite
References23
Newest
Published on Aug 1, 1999in Human Pathology2.74
Cinthia B. Drachenberg54
Estimated H-index: 54
(UMB: University of Maryland, Baltimore),
Christian O. Beskow2
Estimated H-index: 2
(UMB: University of Maryland, Baltimore)
+ 7 AuthorsJohn C. Papadimitriou47
Estimated H-index: 47
(UMB: University of Maryland, Baltimore)
Human polyoma virus (PV) interstitial nephritis occurs in immunosuppressed patients after reactivation of latent virus in renal epithelium. Currently, there is neither general consensus about the incidence of clinically significant PV infection in renal transplants nor conclusive evidence determining its significance in the long-term graft outcome. We evaluated 601 renal transplant biopsy specimens (from 365 patients) by routine light microscopy and immunoperoxidase stains with antibody against ...
Published on May 1, 1999in Journal of The American Society of Nephrology8.55
Volker Nickeleit11
Estimated H-index: 11
,
Hans H. Hirsch60
Estimated H-index: 60
+ 5 AuthorsMichael J. Mihatsch71
Estimated H-index: 71
(University of Basel)
Abstract . Polyomavirus (PV) exceptionally causes a morphologically manifest renal allograft infection. Five such cases were encountered in this study, and were followed between 40 and 330 d during persistent PV renal allograft infection. Transplant (Tx) control groups without PV graft infection were analyzed for comparison. Tissue and urine samples were evaluated by light microscopy, immunohistochemistry, electron microscopy, and PCR. The initial diagnosis of PV infection with the BK strain was...
Published on Apr 1, 1999in American Journal of Pathology3.76
Mark A. van Gorder2
Estimated H-index: 2
(Harvard University),
Patricia Della Pelle10
Estimated H-index: 10
(Harvard University)
+ 3 AuthorsRobert B. Colvin99
Estimated H-index: 99
(Harvard University)
Polyoma virus infection causes acute interstitial nephritis and ureteral stenosis in humans but has rarely been noted in other species. In the present study, a hitherto unknown polyoma virus was detected in 12 of 57 cynomolgus monkeys after 3 to 11 weeks of immunosuppression given to promote acceptance of renal allografts or xenografts. This virus, termed cynomolgus polyoma virus (CPV), is antigenically and genomically related to simian virus 40 (SV40). The tubular epithelial nuclei of the colle...
Published on Mar 1, 1999in Transplantation4.59
Isabelle Binet19
Estimated H-index: 19
(University of Basel),
Volker Nickeleit11
Estimated H-index: 11
+ 5 AuthorsThiel G34
Estimated H-index: 34
(University of Basel)
Background. Manifest polyomavirus (PV) renal graft infection is a rare complication. We diagnosed 5 cases among 70 kidney recipients undergoing transplants since December 1995; however, there were no cases at our institution before December 1995. Method. To identify risk factors promoting manifest PV graft infection, we compared those 5 patients with kidney recipients who had signs of PV replication but no manifest graft infection (n=23, control group). PV replication was judged by the presence ...
Published on Jan 1, 1999in Transplantation4.59
Parmjeet Randhawa62
Estimated H-index: 62
,
Sydney D. Finkelstein50
Estimated H-index: 50
+ 5 AuthorsAnthony J. Demetris92
Estimated H-index: 92
Background. Asymptomatic polyoma virus infection documented by urine cytology or serology is well known, but the clinical course of biopsy-proven interstitial nephritis is not well defined. Methods. Twenty-two cases were identified by histology, immunostaining, in situ hybridization, electron microscopy, or polymerase chain reaction. Results. The clinical features mimicked acute rejection (n=19), chronic rejection with incidental diagnosis at nephrectomy (n=2), or drug toxicity (n=1). Histology ...
Published on Jan 1, 1999in Journal of Nephrology3.70
S Boubenider5
Estimated H-index: 5
,
Christian Hiesse23
Estimated H-index: 23
+ 3 AuthorsBernard Charpentier45
Estimated H-index: 45
Published on Jan 1, 1998in Kidney & Blood Pressure Research2.12
Volker Nickeleit11
Estimated H-index: 11
(University of Basel),
Matthias Zeiler53
Estimated H-index: 53
(University of Basel)
+ 2 AuthorsMichael J. Mihatsch71
Estimated H-index: 71
(University of Basel)
Published on Dec 1, 1997in The Journal of Infectious Diseases5.04
Keerti V. Shah77
Estimated H-index: 77
(NIH: National Institutes of Health),
Richard W. Daniel34
Estimated H-index: 34
(NIH: National Institutes of Health)
+ 1 AuthorsJames J. Goedert94
Estimated H-index: 94
(NIH: National Institutes of Health)
Recent reports of the detection of simian virus 40 (SV40) nucleotide sequences in ependymomas, choroid plexus tumors, osteosarcomas, and mesotheliomas have raised the possibility that SV40, which naturally infects Asian macaques, is circulating among humans. This possibility was examined by performing polymerase chain reaction assays on urine samples of 166 homosexual men, 88 of them human immunodeficiency virus (HIV)-seropositive, for genomic sequences of SV40 as well as of human polyomaviruses...
Published on Dec 1, 1997in Journal of The American Society of Nephrology8.55
Robert B. Colvin99
Estimated H-index: 99
,
Arthur H. Cohen32
Estimated H-index: 32
+ 12 AuthorsAnne S. Lindblad5
Estimated H-index: 5
This study was designed to evaluate the pathologic criteria used for acute renal allograft rejection that were devel- oped by a panel of renal pathologists participating in the Cooperative Clinical Trials in Transplantation, a National In- stitutes of Health-supported, multicenter research group. The panel defined three categories of acute rejection. (1) Type I: mononuclear infiltrate in �5% of cortex, a total of at least three tubules with tubulitis in 10 consecutive high-power fields from the ...
Published on Feb 1, 1996in Modern Pathology6.37
Orit Pappo43
Estimated H-index: 43
,
A. J. Demetris28
Estimated H-index: 28
+ 1 AuthorsParmjeet Randhawa62
Estimated H-index: 62
Abstract Human polyoma virus infection was diagnosed by a needle biopsy of the allograft in two kidney transplant recipients. Viral infection was initially suggested by the occurrence of markedly enlarged tubular epithelial cells with nuclear atypia and chromatin basophilia. Confirmatory evidence was obtained by immunohistochemistry in both cases, and electron microscopy in one instance. Case 1 presented as a refractory interstitial nephritis and underwent allograft nephrectomy. Case 2 showed vi...
Cited By268
Newest
Published on Jun 1, 2019in Diagnostic Microbiology and Infectious Disease2.31
Tong Her1
Estimated H-index: 1
,
Ted Elliott Schutzbank1
Estimated H-index: 1
Abstract BK virus (BKV) nephropathy is a serious complication in renal transplant recipients due to the need for immunosuppression. Nearly 50% of renal transplant patients with BKV nephropathy experience a significant loss of function of the transplanted kidney. It is routine practice to screen renal transplant recipients regularly for BK viremia. In this study, we compared the performance of BKV quantitative polymerase chain reaction analyte specific reagents by ELITech and Luminex for measurin...
Published on May 1, 2019
Emrah Günay (UHSA: University of Health Sciences Antigua), Aysin Zeytinoglu9
Estimated H-index: 9
(Ege University)
+ 5 AuthorsHuseyin Toz24
Estimated H-index: 24
(Ege University)
Abstract Introduction BK virus nephropathy is a serious complication that can lead to allograft kidney loss. Excessive immunosuppression increases the risk. We aimed to evaluate whether there is an increased risk of BK viremia and nephropathy in patients who underwent high-dose immunosuppression because of the development of acute rejection in the early period after kidney transplantation. Methods This retrospective cohort study was performed between April 2015 and March 2016. Twenty-nine patien...
Published on Nov 1, 2018in Seminars in Diagnostic Pathology2.08
Helen P. Cathro18
Estimated H-index: 18
(UVA: University of Virginia),
Steven S. Shen19
Estimated H-index: 19
(Houston Methodist Hospital),
Luan D. Truong51
Estimated H-index: 51
(BCM: Baylor College of Medicine)
Abstract The value of histochemical analysis in the diagnosis of medical renal diseases has long been known, and its use continues currently. Depending on the particular disorder in question, a variety of “special” stains may be applied to renal biopsies. These include the periodic acid-Schiff, Masson trichrome, Jones, von Kossa, Verhoeff-van Gieson, Congo Red, and toluidine blue methods, among others. This review considers the application of such techniques in the assessment of vascular, glomer...
Published on Jun 1, 2019in Diagnostic Microbiology and Infectious Disease2.31
Tong Her1
Estimated H-index: 1
,
Ted Elliott Schutzbank1
Estimated H-index: 1
Abstract BK virus (BKV) nephropathy is a serious complication in renal transplant recipients due to the need for immunosuppression. Nearly 50% of renal transplant patients with BKV nephropathy experience a significant loss of function of the transplanted kidney. It is routine practice to screen renal transplant recipients regularly for BK viremia. In this study, we compared the performance of BKV quantitative polymerase chain reaction analyte specific reagents by ELITech and Luminex for measurin...
Published on Dec 26, 2017in Journal of The American Society of Nephrology8.55
Volker Nickeleit32
Estimated H-index: 32
(UNC: University of North Carolina at Chapel Hill),
Harsharan K. Singh16
Estimated H-index: 16
(UNC: University of North Carolina at Chapel Hill)
+ 14 AuthorsVicki G. Davis12
Estimated H-index: 12
(UNC: University of North Carolina at Chapel Hill)
Polyomavirus nephropathy (PVN) is a common viral infection of renal allografts, with biopsy-proven incidence of approximately 5%. A generally accepted morphologic classification of definitive PVN that groups histologic changes, reflects clinical presentation, and facilitates comparative outcome analyses is lacking. Here, we report a morphologic classification scheme for definitive PVN from the Banff Working Group on Polyomavirus Nephropathy, comprising nine transplant centers in the United State...
Published on Dec 1, 2017in Renal Replacement Therapy
Ai Katsuma4
Estimated H-index: 4
(Jikei University School of Medicine),
Takafumi Yamakawa3
Estimated H-index: 3
(Jikei University School of Medicine)
+ 2 AuthorsTakashi Yokoo23
Estimated H-index: 23
(Jikei University School of Medicine)
Improvements in immunosuppression have reduced acute kidney allograft rejection and clinicians are now seeking ways to prolong allograft survival to 20 years and beyond. The primary cause of kidney allograft loss is still chronic rejection, followed by death with a functioning allograft and primary kidney disease recurrence. Thus, overcoming kidney allograft rejection remains the most important issue. Kidney allograft rejection can be classified into two types: T cell- and antibody-mediated reje...
Published on Dec 1, 2017in Scientific Reports4.01
Chia-Lin Shen1
Estimated H-index: 1
(NYMU: National Yang-Ming University),
An-Hang Yang10
Estimated H-index: 10
(NYMU: National Yang-Ming University)
+ 2 AuthorsChih-Yu Yang9
Estimated H-index: 9
(NYMU: National Yang-Ming University)
BK virus nephropathy (BKVN) and allograft rejection are two distinct disease entities which occur at opposite ends of the immune spectrum. However, they coexist in renal transplant recipients. Predisposing factors for this coexistence remain elusive. We identified nine biopsy-proven BKVN patients with coexisting acute rejection, and 21 patients with BKVN alone. We retrospectively analyzed the dosage and blood concentrations of immunosuppressants during the 3-month period prior to the renal biops...
Published on Dec 1, 2017in Journal of Medical Case Reports
Ana Luisa Figueira Gouvêa3
Estimated H-index: 3
(Federal Fluminense University),
Rachel Ingrid Juliboni Cosendey2
Estimated H-index: 2
(Federal Fluminense University)
+ 8 AuthorsJorge Reis Almeida5
Estimated H-index: 5
(Federal Fluminense University)
Background BK polyomavirus-associated nephropathy is an important cause of post-transplantation renal failure. We present two cases of BK polyomavirus-associated nephropathy who were submitted to contrasting strategies of clinical follow-up to BK polyomavirus reactivation, but progressed to a similar final outcome.
Published on Aug 1, 2017in American Journal of Transplantation7.16
B. J. Nankivell20
Estimated H-index: 20
(Westmead Hospital),
Jasveen Renthawa3
Estimated H-index: 3
+ 3 AuthorsJeremy R. Chapman58
Estimated H-index: 58
(Westmead Hospital)
Reactivation of BK virus in renal allografts causes a destructive chronic infection. This single-center retrospective cohort study describes the evolution of BK virus allograft nephropathy (BKVAN) from 63 kidneys (from 61 patients) using sequential histopathology (454 biopsies, averaging 7.8 ± 2.6 per kidney) followed for 60.1 mo. Uninfected protocol biopsies formulated time-matched control Banff scores (n = 975). Interstitial inflammation occurred in 73% at diagnosis, correlating with viral his...
Published on Apr 1, 2017in Cytopathology1.47
Alana Durayski Ranzi3
Estimated H-index: 3
(UFCSPA: Universidade Federal de Ciências da Saúde de Porto Alegre),
Gisele Orlandi Introíni1
Estimated H-index: 1
(UFCSPA: Universidade Federal de Ciências da Saúde de Porto Alegre)
+ 4 AuthorsClaudia Giuliano Bica4
Estimated H-index: 4
(UFCSPA: Universidade Federal de Ciências da Saúde de Porto Alegre)
Objective The purpose of the present, prospective, cohort study was to monitor urine cytology samples from recipients of renal transplants to search for the occurrence of decoy cells and degenerated inclusion-bearing cells with an aim to correlate the existence of these cells with molecular detection of polyomavirus BK (BKV) DNA in urine. Material and methods This study included patients who underwent renal transplantation. Patients had their urine tested quarterly, during the first year post-tr...
View next paperNew human papovavirus (B.K.) isolated from urine after renal transplantation.