Epidemiology of and Risk Factors for BK Polyomavirus Replication and Nephropathy in Pediatric Renal Transplant Recipients

An International CERTAIN Registry Study

Britta Höcker, Lukas Schneble, Luisa Murer, Andrea Carraro, Lars Pape, Birgitta Kranz, Jun Oh, Matthias Zirngibl, Luca Dello Strologo, Anja Büscher, Lutz T Weber, Atif Awan, Martin Pohl, Martin Bald, Nikoleta Printza, Krisztina Rusai, Licia Peruzzi, Rezan Topaloglu, Alexander Fichtner, Kai Krupka & 5 others Lennart Köster, Thomas Bruckner, Paul Schnitzler, Hans H Hirsch, Burkhard Tönshoff

Research output: Contribution to journalArticle

Abstract

BACKGROUND: BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking.

METHODS: We analyzed data of 313 patients in the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, with an observation period of 3.3 years (range, 1 - 5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score.

RESULTS: Presumptive BKPyVAN (defined as sustained (>3 weeks) high-level BK viremia >10 copies/mL) within 5 years posttransplant occurred in 49/311 (15.8%) of patients, and biopsy-proven BKPyVAN in 14/313 (4.5%). BKPyV viremia was observed in 115/311 patients (36.7%), of whom 11 of 115 (9.6%) developed viremia late, ie, after the second year posttransplant. In 6/48 patients (12.5%) with high-level viremia and in 3/14 (21.4%) with BKPyVAN this respective event occurred late. According to multivariable analysis, BKPyV viremia and/or BKPyVAN were associated with a higher net state of immunosuppression (OR 1.3, p<0.01) and with tacrolimus- vs. ciclosporin-based immunosuppression (OR 3.6, p<0.01), but also with younger recipient age (OR 1.1 per year younger, p<0.001) and obstructive uropathy (OR 12.4, p<0.01) as primary renal disease.

CONCLUSIONS: Uncontrolled BKPyV replication affects a significant proportion of pediatric renal transplant recipients, and is associated with unique features of epidemiology and risk factors such as young recipient age, obstructive uropathy and overall intensity of immunosuppressive therapy. BKPyV surveillance should be considered beyond 2 years posttransplant in pediatric patients at higher risk.

Original languageEnglish
JournalTransplantation
DOIs
Publication statusE-pub ahead of print - Aug 20 2018

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BK Virus
Viremia
Registries
Epidemiology
Pediatrics
Transplants
Kidney
Immunosuppressive Agents
Immunosuppression
Tacrolimus
Cyclosporine
Renal Insufficiency
Allografts
Observation
Transplant Recipients
Biopsy
Therapeutics

Cite this

Epidemiology of and Risk Factors for BK Polyomavirus Replication and Nephropathy in Pediatric Renal Transplant Recipients : An International CERTAIN Registry Study. / Höcker, Britta; Schneble, Lukas; Murer, Luisa; Carraro, Andrea; Pape, Lars; Kranz, Birgitta; Oh, Jun; Zirngibl, Matthias; Dello Strologo, Luca; Büscher, Anja; Weber, Lutz T; Awan, Atif; Pohl, Martin; Bald, Martin; Printza, Nikoleta; Rusai, Krisztina; Peruzzi, Licia; Topaloglu, Rezan; Fichtner, Alexander; Krupka, Kai; Köster, Lennart; Bruckner, Thomas; Schnitzler, Paul; Hirsch, Hans H; Tönshoff, Burkhard.

In: Transplantation, 20.08.2018.

Research output: Contribution to journalArticle

Höcker, B, Schneble, L, Murer, L, Carraro, A, Pape, L, Kranz, B, Oh, J, Zirngibl, M, Dello Strologo, L, Büscher, A, Weber, LT, Awan, A, Pohl, M, Bald, M, Printza, N, Rusai, K, Peruzzi, L, Topaloglu, R, Fichtner, A, Krupka, K, Köster, L, Bruckner, T, Schnitzler, P, Hirsch, HH & Tönshoff, B 2018, 'Epidemiology of and Risk Factors for BK Polyomavirus Replication and Nephropathy in Pediatric Renal Transplant Recipients: An International CERTAIN Registry Study', Transplantation. https://doi.org/10.1097/TP.0000000000002414
Höcker, Britta ; Schneble, Lukas ; Murer, Luisa ; Carraro, Andrea ; Pape, Lars ; Kranz, Birgitta ; Oh, Jun ; Zirngibl, Matthias ; Dello Strologo, Luca ; Büscher, Anja ; Weber, Lutz T ; Awan, Atif ; Pohl, Martin ; Bald, Martin ; Printza, Nikoleta ; Rusai, Krisztina ; Peruzzi, Licia ; Topaloglu, Rezan ; Fichtner, Alexander ; Krupka, Kai ; Köster, Lennart ; Bruckner, Thomas ; Schnitzler, Paul ; Hirsch, Hans H ; Tönshoff, Burkhard. / Epidemiology of and Risk Factors for BK Polyomavirus Replication and Nephropathy in Pediatric Renal Transplant Recipients : An International CERTAIN Registry Study. In: Transplantation. 2018.
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title = "Epidemiology of and Risk Factors for BK Polyomavirus Replication and Nephropathy in Pediatric Renal Transplant Recipients: An International CERTAIN Registry Study",
abstract = "BACKGROUND: BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking.METHODS: We analyzed data of 313 patients in the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, with an observation period of 3.3 years (range, 1 - 5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score.RESULTS: Presumptive BKPyVAN (defined as sustained (>3 weeks) high-level BK viremia >10 copies/mL) within 5 years posttransplant occurred in 49/311 (15.8{\%}) of patients, and biopsy-proven BKPyVAN in 14/313 (4.5{\%}). BKPyV viremia was observed in 115/311 patients (36.7{\%}), of whom 11 of 115 (9.6{\%}) developed viremia late, ie, after the second year posttransplant. In 6/48 patients (12.5{\%}) with high-level viremia and in 3/14 (21.4{\%}) with BKPyVAN this respective event occurred late. According to multivariable analysis, BKPyV viremia and/or BKPyVAN were associated with a higher net state of immunosuppression (OR 1.3, p<0.01) and with tacrolimus- vs. ciclosporin-based immunosuppression (OR 3.6, p<0.01), but also with younger recipient age (OR 1.1 per year younger, p<0.001) and obstructive uropathy (OR 12.4, p<0.01) as primary renal disease.CONCLUSIONS: Uncontrolled BKPyV replication affects a significant proportion of pediatric renal transplant recipients, and is associated with unique features of epidemiology and risk factors such as young recipient age, obstructive uropathy and overall intensity of immunosuppressive therapy. BKPyV surveillance should be considered beyond 2 years posttransplant in pediatric patients at higher risk.",
author = "Britta H{\"o}cker and Lukas Schneble and Luisa Murer and Andrea Carraro and Lars Pape and Birgitta Kranz and Jun Oh and Matthias Zirngibl and {Dello Strologo}, Luca and Anja B{\"u}scher and Weber, {Lutz T} and Atif Awan and Martin Pohl and Martin Bald and Nikoleta Printza and Krisztina Rusai and Licia Peruzzi and Rezan Topaloglu and Alexander Fichtner and Kai Krupka and Lennart K{\"o}ster and Thomas Bruckner and Paul Schnitzler and Hirsch, {Hans H} and Burkhard T{\"o}nshoff",
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publisher = "Lippincott Williams and Wilkins",

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TY - JOUR

T1 - Epidemiology of and Risk Factors for BK Polyomavirus Replication and Nephropathy in Pediatric Renal Transplant Recipients

T2 - An International CERTAIN Registry Study

AU - Höcker, Britta

AU - Schneble, Lukas

AU - Murer, Luisa

AU - Carraro, Andrea

AU - Pape, Lars

AU - Kranz, Birgitta

AU - Oh, Jun

AU - Zirngibl, Matthias

AU - Dello Strologo, Luca

AU - Büscher, Anja

AU - Weber, Lutz T

AU - Awan, Atif

AU - Pohl, Martin

AU - Bald, Martin

AU - Printza, Nikoleta

AU - Rusai, Krisztina

AU - Peruzzi, Licia

AU - Topaloglu, Rezan

AU - Fichtner, Alexander

AU - Krupka, Kai

AU - Köster, Lennart

AU - Bruckner, Thomas

AU - Schnitzler, Paul

AU - Hirsch, Hans H

AU - Tönshoff, Burkhard

PY - 2018/8/20

Y1 - 2018/8/20

N2 - BACKGROUND: BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking.METHODS: We analyzed data of 313 patients in the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, with an observation period of 3.3 years (range, 1 - 5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score.RESULTS: Presumptive BKPyVAN (defined as sustained (>3 weeks) high-level BK viremia >10 copies/mL) within 5 years posttransplant occurred in 49/311 (15.8%) of patients, and biopsy-proven BKPyVAN in 14/313 (4.5%). BKPyV viremia was observed in 115/311 patients (36.7%), of whom 11 of 115 (9.6%) developed viremia late, ie, after the second year posttransplant. In 6/48 patients (12.5%) with high-level viremia and in 3/14 (21.4%) with BKPyVAN this respective event occurred late. According to multivariable analysis, BKPyV viremia and/or BKPyVAN were associated with a higher net state of immunosuppression (OR 1.3, p<0.01) and with tacrolimus- vs. ciclosporin-based immunosuppression (OR 3.6, p<0.01), but also with younger recipient age (OR 1.1 per year younger, p<0.001) and obstructive uropathy (OR 12.4, p<0.01) as primary renal disease.CONCLUSIONS: Uncontrolled BKPyV replication affects a significant proportion of pediatric renal transplant recipients, and is associated with unique features of epidemiology and risk factors such as young recipient age, obstructive uropathy and overall intensity of immunosuppressive therapy. BKPyV surveillance should be considered beyond 2 years posttransplant in pediatric patients at higher risk.

AB - BACKGROUND: BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking.METHODS: We analyzed data of 313 patients in the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, with an observation period of 3.3 years (range, 1 - 5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score.RESULTS: Presumptive BKPyVAN (defined as sustained (>3 weeks) high-level BK viremia >10 copies/mL) within 5 years posttransplant occurred in 49/311 (15.8%) of patients, and biopsy-proven BKPyVAN in 14/313 (4.5%). BKPyV viremia was observed in 115/311 patients (36.7%), of whom 11 of 115 (9.6%) developed viremia late, ie, after the second year posttransplant. In 6/48 patients (12.5%) with high-level viremia and in 3/14 (21.4%) with BKPyVAN this respective event occurred late. According to multivariable analysis, BKPyV viremia and/or BKPyVAN were associated with a higher net state of immunosuppression (OR 1.3, p<0.01) and with tacrolimus- vs. ciclosporin-based immunosuppression (OR 3.6, p<0.01), but also with younger recipient age (OR 1.1 per year younger, p<0.001) and obstructive uropathy (OR 12.4, p<0.01) as primary renal disease.CONCLUSIONS: Uncontrolled BKPyV replication affects a significant proportion of pediatric renal transplant recipients, and is associated with unique features of epidemiology and risk factors such as young recipient age, obstructive uropathy and overall intensity of immunosuppressive therapy. BKPyV surveillance should be considered beyond 2 years posttransplant in pediatric patients at higher risk.

U2 - 10.1097/TP.0000000000002414

DO - 10.1097/TP.0000000000002414

M3 - Article

JO - Transplantation

JF - Transplantation

SN - 0041-1337

ER -