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Hans H Hirsch - One of the best experts on this subject based on the ideXlab platform.
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Reducing calcineurin inhibitor first for treating BK polyomavirus replication after kidney transplantation: long-term outcomes.
Nephrology dialysis transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2018Co-Authors: Nicole Bischof, Hans H Hirsch, Michael Dickenmann, Jurg Steiger, Caroline Wehmeier, Patricia Amico, Patricia Hirt-minkowski, Thomas Menter, Hopfer Helmut, Stefan SchaubAbstract:Background Reducing immunosuppression is the mainstay of treating BK polyomavirus (BKPyV) viraemia after kidney transplantation, but the best approach, efficacy and impact are undefined. We established a standard operating procedure (SOP) treating BKPyV viraemia based on first reducing calcineurin inhibitor ('CNI first'). The aim of this study was to investigate long-term outcomes in 644 consecutive transplantations using this SOP. Methods Patients were monitored for active BKPyV infection by urinary Decoy Cells and, if positive, by BKPyV viraemia. In case of sustained BKPyV viraemia >1000 copies/mL, immunosuppression was reduced stepwise according to the SOP. Patients were classified as 'no Decoy Cells' [n = 432 (66%)], 'Decoy Cells/no viraemia' [n = 107 (17%)] and 'viraemia' [n = 105 (17%)]. Results At 6-years post-transplant, graft survival was ∼84%, the clinical rejection rate was ∼25% and they were not different among the three groups (P = 0.14; P = 0.91). The median estimated glomerular filtration rate at the last follow-up was similar (range 49-53 mL/min, P = 0.08). Of 105 viraemic patients, 101 (96%) cleared BKPyV viraemia. In 39% of patients, viraemia clearance followed a tacrolimus reduction. A reduction of mycophenolic acid was required in 43% and discontinuation in 3%. No short-term graft loss was directly attributable to BKPyV-associated nephropathy. After a median follow-up of 5 years after clearance of BKPyV viraemia, 11/101 patients (11%) developed clinical rejection: 7 (7%) T-cell-mediated rejection and 4 (4%) antibody-mediated rejection (ABMR). Conclusions Immunosuppression reduction based on 'CNI first' leads to similar long-term outcomes in patients with/without BKPyV viraemia and is associated with a low risk for ABMR after clearance of BKPyV viraemia. Randomized trials are needed to compare the risks and benefits of immunosuppression reduction strategies in kidney transplant patients with BKPyV viraemia.
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Co-incident BK and Epstein-Barr virus replication in a 3-year-old immunocompetent boy.
Clinical nephrology, 2014Co-Authors: Christian Breuer, Hans H Hirsch, Andrea Hinsch, Johannes Hiort, Peter DalquenAbstract:We present a unique case of infectious mononucleosis attended with transient asymptomatic BK virus (BKV) manifestation in the urine of an immunocompetent caucasian boy without kidney dysfunction. The urine sediment showed abundant Decoy Cells initially misdiagnosed as malignant cancer Cells. This case demonstrates that the occurrence of polyoma-BKV bearing Decoy Cells is self-limiting and not necessarily associated with overt kidney disease in an immunocompetent child. The shedding of Decoy Cells into the urine might be promoted by viral co-infections modulating the host's immune response such as infectious mononucleosis.
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reducing immunosuppression preserves allograft function in presumptive and definitive polyomavirus associated nephropathy
American Journal of Transplantation, 2010Co-Authors: Stefan Schaub, Hans H Hirsch, Michael Dickenmann, M J Mihatsch, Jurg Steiger, Helmut Hopfer, Michael MayrAbstract:Early detection of polyomavirus BK (BKV) viremia and reduction of immunosuppression is recommended for preventing polyomavirus-associated nephropathy (PyVAN), but systematic histological evaluations were not performed in previous studies. We routinely screen for Decoy Cells and, if positive, measure plasma BKV-loads. In a cohort of 203 consecutive renal transplantations performed from 2005-2008, 38 patients (19%) developed BKV-viremia and were treated with reduction of immunosuppression. Based on subsequent allograft biopsy results and peak BKV-viremia, patients were assigned to three groups: (i) definitive PyVAN (n = 13), (ii) presumptive PyVAN defined by plasma BKV-loads of ? 4 log(10) copies/ml (n = 17) and (iii) low BKV-viremia (n = 8). Clearance of BKV-viremia was achieved in 35/38 patients (92%) and subsequent clinical rejection occurred in 3/35 patients (8.6%), both without any difference among the groups. Patients with definitive PyVAN had higher peak plasma BKV-loads and required longer time for clearance (8.8 vs. 4.6 vs. 2.9 months; p = 0.001). However, allograft function remained stable from baseline to last follow-up at 34 months (range 18-60) in all three groups with median serum creatinine of 1.6 mg/dl, 1.6 mg/dl and 1.3 mg/dl, respectively. We conclude that screening for BKV-replication and reduction of immunosuppression is an effective strategy to preserve medium-term allograft function even in patients developing definitive PyVAN.
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Polyomavirus BK versus JC replication and nephropathy in renal transplant recipients: a prospective evaluation.
Transplantation, 2007Co-Authors: Cinthia B. Drachenberg, Hans H Hirsch, John C. Papadimitriou, Rainer Gosert, Ravinder K. Wali, R. Munivenkatappa, J Nogueira, Charles B. Cangro, Abdolreza Haririan, Susan R. MendleyAbstract:BACKGROUND JC virus (JCV) viruria is more common than BK virus (BKV) viruria in healthy individuals but in kidney transplants (KT), polyomavirus nephropathy (PVAN) is primarily caused by BKV. Few cases of PVAN have been attributed to JCV. Systematic studies on JCV replication in KT are lacking. METHODS Out of a cohort of KT patients screened with urine cytology, patients shedding Decoy Cells were studied (n=103). Molecular studies demonstrated BKV, JCV, or BKV+JCV shedding in 58 (56.3%), 28 (27.2%), and 17 (16.5%), respectively. Biopsy was performed when Decoy Cells persisted 2 months or serum creatinine increased >20%. RESULTS BKV viruria was strongly associated with BKV viremia (93%), PVAN (48%, P=0.01) and graft loss (P=0.03). Higher BKV viremia correlated with graft dysfunction (P=0.01), more advanced histological pattern of PVAN (P or =10,000 copies/mL was significantly associated with histologically confirmed PVAN (P=0.0001). Reduction of immunosuppression lead to disappearance of Decoy Cells in patients shedding BK (>93%). JCV viruria, was more often asymptomatic (P=0.002) and affected older patients (P=0.02). JCV PVAN was less common (21.4%) and was characterized by sparse cytopathic changes but significant inflammation and fibrosis. JCV viremia was rare (14.2%), transient, and low (mean 2.0E+03/mL). After reduction of immunosuppression Decoy Cells persisted in >50% of patients with JCV (P=0.0001), but no graft loss occurred. During the period of the current study, the incidence of BKV-PVAN was 5.5% and the incidence of JCV-PVAN was 0.9%. CONCLUSIONS The data point to significant differences of BKV and JCV biology regarding replication and disease in KT patients, with important implications for screening and management.
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polyomavirus bk versus jc replication and nephropathy in renal transplant recipients a prospective evaluation
Transplantation, 2007Co-Authors: Cinthia B. Drachenberg, Hans H Hirsch, John C. Papadimitriou, Rainer Gosert, Ravinder K. Wali, R. Munivenkatappa, J Nogueira, Charles B. Cangro, Abdolreza Haririan, Susan R. MendleyAbstract:Background. JC virus (JCV) viruria is more common than BK virus (BKV) viruria in healthy individuals but in kidney transplants (KT), polyomavirus nephropathy (PVAN) is primarily caused by BKV. Few cases of PVAN have been attributed to JCV. Systematic studies on JCV replication in KT are lacking. Methods. Out of a cohort of KT patients screened with urine cytology, patients shedding Decoy Cells were studied (n=103). Molecular studies demonstrated BKV, JCV, or BKV+JCV shedding in 58 (56.3%), 28 (27.2%), and 17 (16.5%), respectively. Biopsy was performed when Decoy Cells persisted 2 months or serum creatinine increased >20%. Results. BKV viruria was strongly associated with BKV viremia (93%), PVAN (48%, P=0.01) and graft loss (P=0.03). Higher BKV viremia correlated with graft dysfunction (P=0.01), more advanced histological pattern of PVAN (P 93%). JCV viruria, was more often asymptomatic (P=0.002) and affected older patients (P=0.02). JCV PVAN was less common (21.4%) and was characterized by sparse cytopathic changes but significant inflammation and fibrosis. JCV viremia was rare (14.2%), transient, and low (mean 2.0E+03/mL). After reduction of immunosuppression Decoy Cells persisted in >50% of patients with JCV (P=0.0001), but no graft loss occurred. During the period of the current study, the incidence of BKV-PVAN was 5.5% and the incidence of JCV-PVAN was 0.9%. Conclusions. The data point to significant differences of BKV and JCV biology regarding replication and disease in KT patients, with important implications for screening and management.
Renzo Boldorini - One of the best experts on this subject based on the ideXlab platform.
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Primary trichodysplasia spinulosa polyomavirus infection in a kidney transplant child displaying virus-infected Decoy Cells in the urine.
Journal of medical virology, 2019Co-Authors: Cinzia Borgogna, Silvia Albertini, Elisa Zavattaro, Federica Veronese, Licia Peruzzi, Els Van Der Meijden, Mariet C.w. Feltkamp, Antonella Tosoni, Alessandro Volpe, Renzo BoldoriniAbstract:We report a case of primary trichodysplasia spinulosa (TS) infection in a kidney transplant child and describe for the first time the presence of degenerated TS-associated polyomavirus (TSPyV)-infected Cells in a TS patient's urine that are morphologically different from BK or JC polyomavirus-infected Decoy Cells.
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Latent human polyomavirus infection in pregnancy: investigation of possible transplacental transmission.
Pathology, 2008Co-Authors: Renzo Boldorini, Claudia Veggiani, Elena Amoruso, Sara Allegrini, Umberto Miglio, Alessia Paganotti, Raffaella Ribaldone, Guido MongaAbstract:Summary Aims The purpose of the study was to investigate the transplacental transmission of the human polyomaviruses JCV and BKV. Methods Urine and blood samples from 300 pregnant women underwent cytological analysis to search for 'Decoy Cells', nested PCR to identify presence and genotype of isolated polyomaviruses, and sequence analysis of the transcription control region. Nested PCR was also used to study the umbilical cord blood of all their newborns. Results Decoy Cells were identified in only one urine sample (1/300; 0.33%); polyomavirus DNA was detected in 80 urine samples (26.6%) corresponding to BKV alone in 28 samples (9.3%), JCV alone in 49 samples (16.3%) and both JCV-BKV in three samples (1%). Blood samples were positive in 17 cases (5.6%), corresponding to BKV alone in 10 (3.3%), and JCV alone in 7 (2.3%). Rearrangements of the transcription control region were found in only one urinary JCV strain, consisting of the insertion of 13 bp at D block, whereas point mutations were identified in 11 BKV and 11 JCV strains detected from urine. Sequence analysis of the BKV strains detected in blood samples revealed a 20 bp insertion of P block (P42–61) in human chromosomes 20 (five cases) and 14 (three cases); two JCV strains had single bp point mutations. The search for polyomavirus DNA in umbilical cord blood samples was always negative. Conclusions Polyomavirus DNA was frequently detected in pregnancy, whereas genomic rearrangements were rare, and no evidence of transplacental transmission of polyomavirus was obtained.
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Are Sequence Variations in the BK Virus Control Region Essential for the Development of Polyomavirus Nephropathy
American journal of clinical pathology, 2005Co-Authors: Renzo Boldorini, Claudia Veggiani, Diana Barco, Ernesto Turello, Guido MongaAbstract:BK virus replication is regulated by the noncoding control region (NCCR); major NCCR rearrangements could modify the strength of viral replication, having a role in the development of polyomavirus-associated nephropathy (PAN). Urine (n = 34), blood (n = 32), and renal biopsy samples (n = 13) from 5 transplant recipients with PAN underwent nested polymerase chain reaction to search for the NCCR region. Sequence analysis was performed on all NCCR fragments obtained. Decoy Cells were evaluated semiquantitatively in urine and PAN staged in renal biopsy specimens; the results were related to the presence and type of NCCR sequence variations. Major NCCR rearrangements were found in urine (9/75 [12%]), blood (7/30 [23%]), and renal biopsy (4/15 [27%]) samples in 3 cases; 2 cases had only unrearranged strains. Neither the detection and number of Decoy Cells nor the PAN stage were related to the specific type of NCCR sequence rearrangements. NCCR rearrangements do not seem essential for the development of PAN.
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Periodic Assessment of Urine and Serum by Cytology and Molecular Biology as a Diagnostic Tool for BK Virus Nephropathy in Renal Transplant Patients
Acta cytologica, 2005Co-Authors: Renzo Boldorini, Maddalena Brustia, Claudia Veggiani, Diana Barco, Silvano Andorno, Guido MongaAbstract:OBJECTIVE To investigate the significance of polyomavirus (PV) viruria and viremia by morphologic, immunohistochemical and molecular analysis (multiplex nested-polymerase chain reaction) in renal transplant patients. STUDY DESIGN Urine (n=328), serum (n= 53) and renal biopsies (n=24) from renal transplant patients (n=106) were studied. RESULTS Decoy Cells were found in 53 samples (16%) from 19 patients (18%); viral DNA was amplified in all urinary samples and disclosed BK virus (BKV) (n=24), JC virus (JCV) (n=16), and JCV and BKV DNA (n=13). BKV was the prevailing genotype in patients with a high frequency of Decoy cell excretion (p = 0.001). JCV excretion correlated with a low number (p = 0.01) and BKV with a high number of Decoy Cells (p=0.003). PV DNA was amplified from 30/53 serum samples (56.6%); BKV was the prevailing genotype (p = 0.04). On 24 renal biopsies (18 from the Decoy cell-negative and 6 from the Decoy cell-positive group) PV nephropathy (PVN) was identified and BKV DNA amplified in 4 biopsies, all from the group with a high frequency of Decoy cell excretion. PVN was not identified in renal biopsies from the Decoy cell-negative group. CONCLUSION PV infection is frequent in renal transplant patients. The BKV genotype in urine and serum is significantly related to a high frequency and high number of Decoy Cells. PVN occurs only in patients with BKV viremia and a high number and frequency of Decoy cell excretion in urine. In the absence of Decoy Cells, PVN can be excluded. Cytologic analysis of urine is an important diagnostic tool for screening renal transplant patients at risk of PVN.
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Molecular characterization and sequence analysis of polyomavirus BKV-strain in a renal-allograft recipient
Human pathology, 2001Co-Authors: Renzo Boldorini, Guido Monga, Elisabetta Omodeo Zorini, Mirella Fortunato, Monica Bernardi, Anna Suno, Elisabetta Benigni, Gianna MazzuccoAbstract:The significance of polyomavirus (PV) infection was investigated in a 53-year-old patient who underwent renal transplantation and was treated with triple immunosuppressive therapy (tacrolimus, prednisone, and azathioprine). A renal biopsy taken because of the suspicion of acute rejection showed focal inflammatory interstitial infiltration, tubulitis, and tubular cell nuclear changes consistent with the hypothesis of viral infection. Both the tubular and Decoy Cells identified by means of urinalysis positively stained for anti-SV40 antibody. Polymerase chain reaction performed on the DNA extracted from renal tissue and isolated from urine showed the presence of an antigenic variant (AS) of the BKV archetype after sequence analysis of the transcription control region (TCR). On the basis of the diagnosis of BKV infection, immunosuppressive therapy was reduced. The patient's renal function improved and was still stable 8 months later when urinalysis showed only a few Decoy Cells, which were found to be infected by JC but not BK virus. These data suggest that only the BKV, probably favoured by immunosuppressive therapy (tacrolimus), causes renal damage. It is worth underlining that even small and sporadic viral genome mutations may lead to pathologic effects.
Guido Monga - One of the best experts on this subject based on the ideXlab platform.
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Latent human polyomavirus infection in pregnancy: investigation of possible transplacental transmission.
Pathology, 2008Co-Authors: Renzo Boldorini, Claudia Veggiani, Elena Amoruso, Sara Allegrini, Umberto Miglio, Alessia Paganotti, Raffaella Ribaldone, Guido MongaAbstract:Summary Aims The purpose of the study was to investigate the transplacental transmission of the human polyomaviruses JCV and BKV. Methods Urine and blood samples from 300 pregnant women underwent cytological analysis to search for 'Decoy Cells', nested PCR to identify presence and genotype of isolated polyomaviruses, and sequence analysis of the transcription control region. Nested PCR was also used to study the umbilical cord blood of all their newborns. Results Decoy Cells were identified in only one urine sample (1/300; 0.33%); polyomavirus DNA was detected in 80 urine samples (26.6%) corresponding to BKV alone in 28 samples (9.3%), JCV alone in 49 samples (16.3%) and both JCV-BKV in three samples (1%). Blood samples were positive in 17 cases (5.6%), corresponding to BKV alone in 10 (3.3%), and JCV alone in 7 (2.3%). Rearrangements of the transcription control region were found in only one urinary JCV strain, consisting of the insertion of 13 bp at D block, whereas point mutations were identified in 11 BKV and 11 JCV strains detected from urine. Sequence analysis of the BKV strains detected in blood samples revealed a 20 bp insertion of P block (P42–61) in human chromosomes 20 (five cases) and 14 (three cases); two JCV strains had single bp point mutations. The search for polyomavirus DNA in umbilical cord blood samples was always negative. Conclusions Polyomavirus DNA was frequently detected in pregnancy, whereas genomic rearrangements were rare, and no evidence of transplacental transmission of polyomavirus was obtained.
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Are Sequence Variations in the BK Virus Control Region Essential for the Development of Polyomavirus Nephropathy
American journal of clinical pathology, 2005Co-Authors: Renzo Boldorini, Claudia Veggiani, Diana Barco, Ernesto Turello, Guido MongaAbstract:BK virus replication is regulated by the noncoding control region (NCCR); major NCCR rearrangements could modify the strength of viral replication, having a role in the development of polyomavirus-associated nephropathy (PAN). Urine (n = 34), blood (n = 32), and renal biopsy samples (n = 13) from 5 transplant recipients with PAN underwent nested polymerase chain reaction to search for the NCCR region. Sequence analysis was performed on all NCCR fragments obtained. Decoy Cells were evaluated semiquantitatively in urine and PAN staged in renal biopsy specimens; the results were related to the presence and type of NCCR sequence variations. Major NCCR rearrangements were found in urine (9/75 [12%]), blood (7/30 [23%]), and renal biopsy (4/15 [27%]) samples in 3 cases; 2 cases had only unrearranged strains. Neither the detection and number of Decoy Cells nor the PAN stage were related to the specific type of NCCR sequence rearrangements. NCCR rearrangements do not seem essential for the development of PAN.
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Periodic Assessment of Urine and Serum by Cytology and Molecular Biology as a Diagnostic Tool for BK Virus Nephropathy in Renal Transplant Patients
Acta cytologica, 2005Co-Authors: Renzo Boldorini, Maddalena Brustia, Claudia Veggiani, Diana Barco, Silvano Andorno, Guido MongaAbstract:OBJECTIVE To investigate the significance of polyomavirus (PV) viruria and viremia by morphologic, immunohistochemical and molecular analysis (multiplex nested-polymerase chain reaction) in renal transplant patients. STUDY DESIGN Urine (n=328), serum (n= 53) and renal biopsies (n=24) from renal transplant patients (n=106) were studied. RESULTS Decoy Cells were found in 53 samples (16%) from 19 patients (18%); viral DNA was amplified in all urinary samples and disclosed BK virus (BKV) (n=24), JC virus (JCV) (n=16), and JCV and BKV DNA (n=13). BKV was the prevailing genotype in patients with a high frequency of Decoy cell excretion (p = 0.001). JCV excretion correlated with a low number (p = 0.01) and BKV with a high number of Decoy Cells (p=0.003). PV DNA was amplified from 30/53 serum samples (56.6%); BKV was the prevailing genotype (p = 0.04). On 24 renal biopsies (18 from the Decoy cell-negative and 6 from the Decoy cell-positive group) PV nephropathy (PVN) was identified and BKV DNA amplified in 4 biopsies, all from the group with a high frequency of Decoy cell excretion. PVN was not identified in renal biopsies from the Decoy cell-negative group. CONCLUSION PV infection is frequent in renal transplant patients. The BKV genotype in urine and serum is significantly related to a high frequency and high number of Decoy Cells. PVN occurs only in patients with BKV viremia and a high number and frequency of Decoy cell excretion in urine. In the absence of Decoy Cells, PVN can be excluded. Cytologic analysis of urine is an important diagnostic tool for screening renal transplant patients at risk of PVN.
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Molecular characterization and sequence analysis of polyomavirus BKV-strain in a renal-allograft recipient
Human pathology, 2001Co-Authors: Renzo Boldorini, Guido Monga, Elisabetta Omodeo Zorini, Mirella Fortunato, Monica Bernardi, Anna Suno, Elisabetta Benigni, Gianna MazzuccoAbstract:The significance of polyomavirus (PV) infection was investigated in a 53-year-old patient who underwent renal transplantation and was treated with triple immunosuppressive therapy (tacrolimus, prednisone, and azathioprine). A renal biopsy taken because of the suspicion of acute rejection showed focal inflammatory interstitial infiltration, tubulitis, and tubular cell nuclear changes consistent with the hypothesis of viral infection. Both the tubular and Decoy Cells identified by means of urinalysis positively stained for anti-SV40 antibody. Polymerase chain reaction performed on the DNA extracted from renal tissue and isolated from urine showed the presence of an antigenic variant (AS) of the BKV archetype after sequence analysis of the transcription control region (TCR). On the basis of the diagnosis of BKV infection, immunosuppressive therapy was reduced. The patient's renal function improved and was still stable 8 months later when urinalysis showed only a few Decoy Cells, which were found to be infected by JC but not BK virus. These data suggest that only the BKV, probably favoured by immunosuppressive therapy (tacrolimus), causes renal damage. It is worth underlining that even small and sporadic viral genome mutations may lead to pathologic effects.
Cinthia B. Drachenberg - One of the best experts on this subject based on the ideXlab platform.
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polyomavirus bk versus jc replication and nephropathy in renal transplant recipients a prospective evaluation
Transplantation, 2007Co-Authors: Cinthia B. Drachenberg, Hans H Hirsch, John C. Papadimitriou, Rainer Gosert, Ravinder K. Wali, R. Munivenkatappa, J Nogueira, Charles B. Cangro, Abdolreza Haririan, Susan R. MendleyAbstract:Background. JC virus (JCV) viruria is more common than BK virus (BKV) viruria in healthy individuals but in kidney transplants (KT), polyomavirus nephropathy (PVAN) is primarily caused by BKV. Few cases of PVAN have been attributed to JCV. Systematic studies on JCV replication in KT are lacking. Methods. Out of a cohort of KT patients screened with urine cytology, patients shedding Decoy Cells were studied (n=103). Molecular studies demonstrated BKV, JCV, or BKV+JCV shedding in 58 (56.3%), 28 (27.2%), and 17 (16.5%), respectively. Biopsy was performed when Decoy Cells persisted 2 months or serum creatinine increased >20%. Results. BKV viruria was strongly associated with BKV viremia (93%), PVAN (48%, P=0.01) and graft loss (P=0.03). Higher BKV viremia correlated with graft dysfunction (P=0.01), more advanced histological pattern of PVAN (P 93%). JCV viruria, was more often asymptomatic (P=0.002) and affected older patients (P=0.02). JCV PVAN was less common (21.4%) and was characterized by sparse cytopathic changes but significant inflammation and fibrosis. JCV viremia was rare (14.2%), transient, and low (mean 2.0E+03/mL). After reduction of immunosuppression Decoy Cells persisted in >50% of patients with JCV (P=0.0001), but no graft loss occurred. During the period of the current study, the incidence of BKV-PVAN was 5.5% and the incidence of JCV-PVAN was 0.9%. Conclusions. The data point to significant differences of BKV and JCV biology regarding replication and disease in KT patients, with important implications for screening and management.
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Polyomavirus BK versus JC replication and nephropathy in renal transplant recipients: a prospective evaluation.
Transplantation, 2007Co-Authors: Cinthia B. Drachenberg, Hans H Hirsch, John C. Papadimitriou, Rainer Gosert, Ravinder K. Wali, R. Munivenkatappa, J Nogueira, Charles B. Cangro, Abdolreza Haririan, Susan R. MendleyAbstract:BACKGROUND JC virus (JCV) viruria is more common than BK virus (BKV) viruria in healthy individuals but in kidney transplants (KT), polyomavirus nephropathy (PVAN) is primarily caused by BKV. Few cases of PVAN have been attributed to JCV. Systematic studies on JCV replication in KT are lacking. METHODS Out of a cohort of KT patients screened with urine cytology, patients shedding Decoy Cells were studied (n=103). Molecular studies demonstrated BKV, JCV, or BKV+JCV shedding in 58 (56.3%), 28 (27.2%), and 17 (16.5%), respectively. Biopsy was performed when Decoy Cells persisted 2 months or serum creatinine increased >20%. RESULTS BKV viruria was strongly associated with BKV viremia (93%), PVAN (48%, P=0.01) and graft loss (P=0.03). Higher BKV viremia correlated with graft dysfunction (P=0.01), more advanced histological pattern of PVAN (P or =10,000 copies/mL was significantly associated with histologically confirmed PVAN (P=0.0001). Reduction of immunosuppression lead to disappearance of Decoy Cells in patients shedding BK (>93%). JCV viruria, was more often asymptomatic (P=0.002) and affected older patients (P=0.02). JCV PVAN was less common (21.4%) and was characterized by sparse cytopathic changes but significant inflammation and fibrosis. JCV viremia was rare (14.2%), transient, and low (mean 2.0E+03/mL). After reduction of immunosuppression Decoy Cells persisted in >50% of patients with JCV (P=0.0001), but no graft loss occurred. During the period of the current study, the incidence of BKV-PVAN was 5.5% and the incidence of JCV-PVAN was 0.9%. CONCLUSIONS The data point to significant differences of BKV and JCV biology regarding replication and disease in KT patients, with important implications for screening and management.
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Urine Cytology Findings of Polyomavirus Infections
Advances in experimental medicine and biology, 2006Co-Authors: Harsharan K. Singh, Lukas Bubendorf, Michael J. Mihatsch, Cinthia B. Drachenberg, Volker NickeleitAbstract:Polyomaviruses of the BK- and JC-strains often remain latent within the transitional cell layer of the bladder, ureters and the renal pelvis as well as in tubular epithelial Cells of the kidney. Slight changes in the immune status and/or an immunocompromised condition can lead to the (re)activation of latent polyomaviruses, especially along the transitional cell layer, resulting in the shedding of viral particles and infected Cells into the urine. A morphologic sign of the (re)activation of polyomaviruses is the detection of typical intranuclear viral inclusion bearing epithelial Cells, so-called "Decoy Cells", in the urine. Decoy Cells often contain polyoma-BK-viruses. The inclusion bearing Cells are easily identified and quantifiable in routine Papanicolaou stained urine cytology specimens. With some experience, Decoy Cells can also be detected in the unstained urinary sediment by phase contrast microscopy. Different morphologic variants of Decoy Cells (types 1 through 4) are described and ancillary techniques (immunohistochemistry, electron microscopy (EM), and fluorescence-in-situ-hybridization (FISH)) for proper identification and characterization are discussed. Special emphasis is placed on the clinical significance of the detection of Decoy Cells as a parameter to assess the risk for disease, i.e., polyoma-BK-virus nephropathy (BKN) in kidney transplant recipients. The sensitivity and specificity of Decoy Cells for diagnosing BKN is 99% and 95%, respectively, the positive predictive value varies between 27% and more than 90%, and the negative predictive value is 99%. The detection of Decoy Cells is compared to other techniques applicable to assess the activation of polyomaviruses in the urine (polymerase chain reaction (PCR) and EM).
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histological patterns of polyomavirus nephropathy correlation with graft outcome and viral load
American Journal of Transplantation, 2004Co-Authors: Cinthia B. Drachenberg, Hans H Hirsch, John C. Papadimitriou, Ravinder K. Wali, J Nogueira, Charles B. Cangro, Susan R. Mendley, Clinton D Crowder, Ayesa N Mian, Emilio RamosAbstract:Polyomavirus-associated nephropathy (PVAN) is a significant cause of allograft loss. The diagnosis requires allograft biopsy, but the impact of the histological features on diagnosis and outcome has not been described. We studied the distribution and extent of PVAN in 90 patients. Viral cytopathic changes, tubular atrophy/fibrosis and inflammation were semi-quantitatively scored and classified into histological patterns. The histological findings were correlated with viruria, viremia and graft survival. PVAN lesions were random, (multi-)focal and affected both cortex and medulla. Areas with PVAN coexisted with areas of unaffected parenchyma. In 36.5% (15/41) of biopsies with multiple tissue cores, discordant findings with PVAN-positive and -negative cores were observed. However, all patients with PVAN had Decoy Cells in urine as well as significant viruria and viremia (mean of 2.5 × 108 and 2.32 × 107 viral copies, respectively). Biopsies showing lesser degrees of renal scarring at the time of diagnosis were associated with, more likely, resolution of the infection, in response to decrease of immunosuppression (p = 0.001). More advanced tubulointerstitial atrophy, active inflammation and higher creatinine level at diagnosis correlated with worse graft outcome (p = 0.0002, 0.0001 and 0.0006). Due to the focal nature of PVAN, correlation of biopsy results with viruria and viremia are required for diagnosis.
Susan R. Mendley - One of the best experts on this subject based on the ideXlab platform.
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Polyomavirus BK versus JC replication and nephropathy in renal transplant recipients: a prospective evaluation.
Transplantation, 2007Co-Authors: Cinthia B. Drachenberg, Hans H Hirsch, John C. Papadimitriou, Rainer Gosert, Ravinder K. Wali, R. Munivenkatappa, J Nogueira, Charles B. Cangro, Abdolreza Haririan, Susan R. MendleyAbstract:BACKGROUND JC virus (JCV) viruria is more common than BK virus (BKV) viruria in healthy individuals but in kidney transplants (KT), polyomavirus nephropathy (PVAN) is primarily caused by BKV. Few cases of PVAN have been attributed to JCV. Systematic studies on JCV replication in KT are lacking. METHODS Out of a cohort of KT patients screened with urine cytology, patients shedding Decoy Cells were studied (n=103). Molecular studies demonstrated BKV, JCV, or BKV+JCV shedding in 58 (56.3%), 28 (27.2%), and 17 (16.5%), respectively. Biopsy was performed when Decoy Cells persisted 2 months or serum creatinine increased >20%. RESULTS BKV viruria was strongly associated with BKV viremia (93%), PVAN (48%, P=0.01) and graft loss (P=0.03). Higher BKV viremia correlated with graft dysfunction (P=0.01), more advanced histological pattern of PVAN (P or =10,000 copies/mL was significantly associated with histologically confirmed PVAN (P=0.0001). Reduction of immunosuppression lead to disappearance of Decoy Cells in patients shedding BK (>93%). JCV viruria, was more often asymptomatic (P=0.002) and affected older patients (P=0.02). JCV PVAN was less common (21.4%) and was characterized by sparse cytopathic changes but significant inflammation and fibrosis. JCV viremia was rare (14.2%), transient, and low (mean 2.0E+03/mL). After reduction of immunosuppression Decoy Cells persisted in >50% of patients with JCV (P=0.0001), but no graft loss occurred. During the period of the current study, the incidence of BKV-PVAN was 5.5% and the incidence of JCV-PVAN was 0.9%. CONCLUSIONS The data point to significant differences of BKV and JCV biology regarding replication and disease in KT patients, with important implications for screening and management.
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polyomavirus bk versus jc replication and nephropathy in renal transplant recipients a prospective evaluation
Transplantation, 2007Co-Authors: Cinthia B. Drachenberg, Hans H Hirsch, John C. Papadimitriou, Rainer Gosert, Ravinder K. Wali, R. Munivenkatappa, J Nogueira, Charles B. Cangro, Abdolreza Haririan, Susan R. MendleyAbstract:Background. JC virus (JCV) viruria is more common than BK virus (BKV) viruria in healthy individuals but in kidney transplants (KT), polyomavirus nephropathy (PVAN) is primarily caused by BKV. Few cases of PVAN have been attributed to JCV. Systematic studies on JCV replication in KT are lacking. Methods. Out of a cohort of KT patients screened with urine cytology, patients shedding Decoy Cells were studied (n=103). Molecular studies demonstrated BKV, JCV, or BKV+JCV shedding in 58 (56.3%), 28 (27.2%), and 17 (16.5%), respectively. Biopsy was performed when Decoy Cells persisted 2 months or serum creatinine increased >20%. Results. BKV viruria was strongly associated with BKV viremia (93%), PVAN (48%, P=0.01) and graft loss (P=0.03). Higher BKV viremia correlated with graft dysfunction (P=0.01), more advanced histological pattern of PVAN (P 93%). JCV viruria, was more often asymptomatic (P=0.002) and affected older patients (P=0.02). JCV PVAN was less common (21.4%) and was characterized by sparse cytopathic changes but significant inflammation and fibrosis. JCV viremia was rare (14.2%), transient, and low (mean 2.0E+03/mL). After reduction of immunosuppression Decoy Cells persisted in >50% of patients with JCV (P=0.0001), but no graft loss occurred. During the period of the current study, the incidence of BKV-PVAN was 5.5% and the incidence of JCV-PVAN was 0.9%. Conclusions. The data point to significant differences of BKV and JCV biology regarding replication and disease in KT patients, with important implications for screening and management.
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histological patterns of polyomavirus nephropathy correlation with graft outcome and viral load
American Journal of Transplantation, 2004Co-Authors: Cinthia B. Drachenberg, Hans H Hirsch, John C. Papadimitriou, Ravinder K. Wali, J Nogueira, Charles B. Cangro, Susan R. Mendley, Clinton D Crowder, Ayesa N Mian, Emilio RamosAbstract:Polyomavirus-associated nephropathy (PVAN) is a significant cause of allograft loss. The diagnosis requires allograft biopsy, but the impact of the histological features on diagnosis and outcome has not been described. We studied the distribution and extent of PVAN in 90 patients. Viral cytopathic changes, tubular atrophy/fibrosis and inflammation were semi-quantitatively scored and classified into histological patterns. The histological findings were correlated with viruria, viremia and graft survival. PVAN lesions were random, (multi-)focal and affected both cortex and medulla. Areas with PVAN coexisted with areas of unaffected parenchyma. In 36.5% (15/41) of biopsies with multiple tissue cores, discordant findings with PVAN-positive and -negative cores were observed. However, all patients with PVAN had Decoy Cells in urine as well as significant viruria and viremia (mean of 2.5 × 108 and 2.32 × 107 viral copies, respectively). Biopsies showing lesser degrees of renal scarring at the time of diagnosis were associated with, more likely, resolution of the infection, in response to decrease of immunosuppression (p = 0.001). More advanced tubulointerstitial atrophy, active inflammation and higher creatinine level at diagnosis correlated with worse graft outcome (p = 0.0002, 0.0001 and 0.0006). Due to the focal nature of PVAN, correlation of biopsy results with viruria and viremia are required for diagnosis.
