Cytomegalovirus Infection in Pediatric Renal Transplantation and the Impact of Chemoprophylaxis With (Val-)Ganciclovir

Britta Höcker; Sebastian Zencke; Kai Krupka; Alexander Fichtner; Lars Pape; Luca Dello Strologo; Isabella Guzzo; Rezan Topaloglu; Birgitta Kranz; Jens König; Martin Bald; Nicholas Webb; Aytül Noyan; Hasan Dursun; Stephen Marks; Fatos Yalcinkaya; Florian Thiel; Heiko Billing; Martin Pohl; Henry Fehrenbach; Thomas Bruckner; Burkhard Tönshoff

doi:10.1097/TP.0000000000000888

Cytomegalovirus Infection in Pediatric Renal Transplantation and the Impact of Chemoprophylaxis With (Val-)Ganciclovir

Britta Höcker, Sebastian Zencke, Kai Krupka, Alexander Fichtner, Lars Pape, Luca Dello Strologo, Isabella Guzzo, Rezan Topaloglu, Birgitta Kranz, Jens König, Martin Bald, Nicholas Webb, Aytül Noyan, Hasan Dursun, Stephen Marks, Fatos Yalcinkaya, Florian Thiel, Heiko Billing, Martin Pohl, Henry FehrenbachThomas Bruckner, Burkhard Tönshoff

Division of Cell Matrix Biology & Regenerative Medicine (L5)

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Cytomegalovirus (CMV) replication and disease, with its associated morbidity and poor transplant outcome, represents a serious threat to transplant recipients. The pediatric kidney transplant population is at a particularly increased risk of CMV infection.

METHODS: We therefore analyzed CMV epidemiology in a large cohort of pediatric renal transplant recipients (n = 242) and assessed the impact of antiviral chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) on CMV replication and morbidity.

RESULTS: While antiviral chemoprophylaxis with VGCV or GCV in patients with a high (D+/R-) or intermediate (D+/R+) CMV risk (n = 82) compared to preemptive therapy (n = 47) had no significant effect on the incidence of CMV syndrome or tissue-invasive disease, chemoprophylaxis was associated with a better preservation of transplant function at 3 years posttransplant (loss of estimated glomerular filtration rate in the chemoprophylaxis cohort, 16.0 ± 3.4 vs. 30.1 ± 4.7 mL/min per 1.73 m(2) in the preemptive therapy cohort, P < 0.05).CMV replication was associated with a more pronounced decline of graft function (difference in estimated glomerular filtration rate of 9.6 mL/min per 1.73 m(2) at 3 years) compared to patients without CMV replication. However, patients undergoing VGCV or GCV chemoprophylaxis had more leukocytopenia.

CONCLUSION: Antiviral chemoprophylaxis with VGCV or GCV in recipients with a high or moderate CMV risk is associated with a better preservation of transplant function. Hence, the prevention of CMV replication in this patient population has the potential to improve transplant outcome.

Original language	English
Pages (from-to)	862-870
Number of pages	9
Journal	Transplantation
Volume	100
Issue number	4
DOIs	https://doi.org/10.1097/TP.0000000000000888
Publication status	Published - Apr 2016

Keywords

Adolescent
Age Factors
Antiviral Agents
Child
Child, Preschool
Cytomegalovirus
Cytomegalovirus Infections
Drug Administration Schedule
Europe
Female
Ganciclovir
Graft Survival
Humans
Immunocompromised Host
Immunosuppressive Agents
Incidence
Kidney Transplantation
Male
Opportunistic Infections
Registries
Retrospective Studies
Risk Assessment
Risk Factors
Time Factors
Treatment Outcome
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

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10.1097/TP.0000000000000888

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Höcker, B., Zencke, S., Krupka, K., Fichtner, A., Pape, L., Dello Strologo, L., Guzzo, I., Topaloglu, R., Kranz, B., König, J., Bald, M., Webb, N., Noyan, A., Dursun, H., Marks, S., Yalcinkaya, F., Thiel, F., Billing, H., Pohl, M., ... Tönshoff, B. (2016). Cytomegalovirus Infection in Pediatric Renal Transplantation and the Impact of Chemoprophylaxis With (Val-)Ganciclovir. Transplantation, 100(4), 862-870. https://doi.org/10.1097/TP.0000000000000888

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title = "Cytomegalovirus Infection in Pediatric Renal Transplantation and the Impact of Chemoprophylaxis With (Val-)Ganciclovir",

abstract = "BACKGROUND: Cytomegalovirus (CMV) replication and disease, with its associated morbidity and poor transplant outcome, represents a serious threat to transplant recipients. The pediatric kidney transplant population is at a particularly increased risk of CMV infection.METHODS: We therefore analyzed CMV epidemiology in a large cohort of pediatric renal transplant recipients (n = 242) and assessed the impact of antiviral chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) on CMV replication and morbidity.RESULTS: While antiviral chemoprophylaxis with VGCV or GCV in patients with a high (D+/R-) or intermediate (D+/R+) CMV risk (n = 82) compared to preemptive therapy (n = 47) had no significant effect on the incidence of CMV syndrome or tissue-invasive disease, chemoprophylaxis was associated with a better preservation of transplant function at 3 years posttransplant (loss of estimated glomerular filtration rate in the chemoprophylaxis cohort, 16.0 ± 3.4 vs. 30.1 ± 4.7 mL/min per 1.73 m(2) in the preemptive therapy cohort, P < 0.05).CMV replication was associated with a more pronounced decline of graft function (difference in estimated glomerular filtration rate of 9.6 mL/min per 1.73 m(2) at 3 years) compared to patients without CMV replication. However, patients undergoing VGCV or GCV chemoprophylaxis had more leukocytopenia.CONCLUSION: Antiviral chemoprophylaxis with VGCV or GCV in recipients with a high or moderate CMV risk is associated with a better preservation of transplant function. Hence, the prevention of CMV replication in this patient population has the potential to improve transplant outcome.",

keywords = "Adolescent, Age Factors, Antiviral Agents, Child, Child, Preschool, Cytomegalovirus, Cytomegalovirus Infections, Drug Administration Schedule, Europe, Female, Ganciclovir, Graft Survival, Humans, Immunocompromised Host, Immunosuppressive Agents, Incidence, Kidney Transplantation, Male, Opportunistic Infections, Registries, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't",

author = "Britta H{\"o}cker and Sebastian Zencke and Kai Krupka and Alexander Fichtner and Lars Pape and {Dello Strologo}, Luca and Isabella Guzzo and Rezan Topaloglu and Birgitta Kranz and Jens K{\"o}nig and Martin Bald and Nicholas Webb and Ayt{\"u}l Noyan and Hasan Dursun and Stephen Marks and Fatos Yalcinkaya and Florian Thiel and Heiko Billing and Martin Pohl and Henry Fehrenbach and Thomas Bruckner and Burkhard T{\"o}nshoff",

year = "2016",

month = apr,

doi = "10.1097/TP.0000000000000888",

language = "English",

volume = "100",

pages = "862--870",

journal = "Transplantation",

issn = "0041-1337",

publisher = "Lippincott Williams & Wilkins",

number = "4",

}

Höcker, B, Zencke, S, Krupka, K, Fichtner, A, Pape, L, Dello Strologo, L, Guzzo, I, Topaloglu, R, Kranz, B, König, J, Bald, M, Webb, N, Noyan, A, Dursun, H, Marks, S, Yalcinkaya, F, Thiel, F, Billing, H, Pohl, M, Fehrenbach, H, Bruckner, T & Tönshoff, B 2016, 'Cytomegalovirus Infection in Pediatric Renal Transplantation and the Impact of Chemoprophylaxis With (Val-)Ganciclovir', Transplantation, vol. 100, no. 4, pp. 862-870. https://doi.org/10.1097/TP.0000000000000888

TY - JOUR

T1 - Cytomegalovirus Infection in Pediatric Renal Transplantation and the Impact of Chemoprophylaxis With (Val-)Ganciclovir

AU - Höcker, Britta

AU - Zencke, Sebastian

AU - Krupka, Kai

AU - Fichtner, Alexander

AU - Pape, Lars

AU - Dello Strologo, Luca

AU - Guzzo, Isabella

AU - Topaloglu, Rezan

AU - Kranz, Birgitta

AU - König, Jens

AU - Bald, Martin

AU - Webb, Nicholas

AU - Noyan, Aytül

AU - Dursun, Hasan

AU - Marks, Stephen

AU - Yalcinkaya, Fatos

AU - Thiel, Florian

AU - Billing, Heiko

AU - Pohl, Martin

AU - Fehrenbach, Henry

AU - Bruckner, Thomas

AU - Tönshoff, Burkhard

PY - 2016/4

Y1 - 2016/4

N2 - BACKGROUND: Cytomegalovirus (CMV) replication and disease, with its associated morbidity and poor transplant outcome, represents a serious threat to transplant recipients. The pediatric kidney transplant population is at a particularly increased risk of CMV infection.METHODS: We therefore analyzed CMV epidemiology in a large cohort of pediatric renal transplant recipients (n = 242) and assessed the impact of antiviral chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) on CMV replication and morbidity.RESULTS: While antiviral chemoprophylaxis with VGCV or GCV in patients with a high (D+/R-) or intermediate (D+/R+) CMV risk (n = 82) compared to preemptive therapy (n = 47) had no significant effect on the incidence of CMV syndrome or tissue-invasive disease, chemoprophylaxis was associated with a better preservation of transplant function at 3 years posttransplant (loss of estimated glomerular filtration rate in the chemoprophylaxis cohort, 16.0 ± 3.4 vs. 30.1 ± 4.7 mL/min per 1.73 m(2) in the preemptive therapy cohort, P < 0.05).CMV replication was associated with a more pronounced decline of graft function (difference in estimated glomerular filtration rate of 9.6 mL/min per 1.73 m(2) at 3 years) compared to patients without CMV replication. However, patients undergoing VGCV or GCV chemoprophylaxis had more leukocytopenia.CONCLUSION: Antiviral chemoprophylaxis with VGCV or GCV in recipients with a high or moderate CMV risk is associated with a better preservation of transplant function. Hence, the prevention of CMV replication in this patient population has the potential to improve transplant outcome.

AB - BACKGROUND: Cytomegalovirus (CMV) replication and disease, with its associated morbidity and poor transplant outcome, represents a serious threat to transplant recipients. The pediatric kidney transplant population is at a particularly increased risk of CMV infection.METHODS: We therefore analyzed CMV epidemiology in a large cohort of pediatric renal transplant recipients (n = 242) and assessed the impact of antiviral chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) on CMV replication and morbidity.RESULTS: While antiviral chemoprophylaxis with VGCV or GCV in patients with a high (D+/R-) or intermediate (D+/R+) CMV risk (n = 82) compared to preemptive therapy (n = 47) had no significant effect on the incidence of CMV syndrome or tissue-invasive disease, chemoprophylaxis was associated with a better preservation of transplant function at 3 years posttransplant (loss of estimated glomerular filtration rate in the chemoprophylaxis cohort, 16.0 ± 3.4 vs. 30.1 ± 4.7 mL/min per 1.73 m(2) in the preemptive therapy cohort, P < 0.05).CMV replication was associated with a more pronounced decline of graft function (difference in estimated glomerular filtration rate of 9.6 mL/min per 1.73 m(2) at 3 years) compared to patients without CMV replication. However, patients undergoing VGCV or GCV chemoprophylaxis had more leukocytopenia.CONCLUSION: Antiviral chemoprophylaxis with VGCV or GCV in recipients with a high or moderate CMV risk is associated with a better preservation of transplant function. Hence, the prevention of CMV replication in this patient population has the potential to improve transplant outcome.

KW - Adolescent

KW - Age Factors

KW - Antiviral Agents

KW - Child

KW - Child, Preschool

KW - Cytomegalovirus

KW - Cytomegalovirus Infections

KW - Drug Administration Schedule

KW - Europe

KW - Female

KW - Ganciclovir

KW - Graft Survival

KW - Humans

KW - Immunocompromised Host

KW - Immunosuppressive Agents

KW - Incidence

KW - Kidney Transplantation

KW - Male

KW - Opportunistic Infections

KW - Registries

KW - Retrospective Studies

KW - Risk Assessment

KW - Risk Factors

KW - Time Factors

KW - Treatment Outcome

KW - Journal Article

KW - Multicenter Study

KW - Research Support, Non-U.S. Gov't

U2 - 10.1097/TP.0000000000000888

DO - 10.1097/TP.0000000000000888

M3 - Article

C2 - 26736017

SN - 0041-1337

VL - 100

SP - 862

EP - 870

JO - Transplantation

JF - Transplantation

IS - 4

ER -

Cytomegalovirus Infection in Pediatric Renal Transplantation and the Impact of Chemoprophylaxis With (Val-)Ganciclovir

Abstract

Keywords

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