Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: Outcome and risk factors for late CMV disease

Background Anti‐thymocyte globulin (ATG) therapy is a risk factor for cytomegalovirus (CMV) disease in renal transplant (RTx) recipients and therefore antiviral prophylaxis is commonly used. We evaluated the outcome of our current policy of 90 days of CMV prophylaxis in seropositive recipients given...

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Veröffentlicht in:Transplant infectious disease 2018-10, Vol.20 (5), p.e12929-n/a
Hauptverfasser: Reusing, Jose O., Feitosa, Emanoela B., Agena, Fabiana, Pierrotti, Lígia C., Azevedo, Luiz S. F., Kotton, Camille N., David‐Neto, Elias
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container_issue 5
container_start_page e12929
container_title Transplant infectious disease
container_volume 20
creator Reusing, Jose O.
Feitosa, Emanoela B.
Agena, Fabiana
Pierrotti, Lígia C.
Azevedo, Luiz S. F.
Kotton, Camille N.
David‐Neto, Elias
description Background Anti‐thymocyte globulin (ATG) therapy is a risk factor for cytomegalovirus (CMV) disease in renal transplant (RTx) recipients and therefore antiviral prophylaxis is commonly used. We evaluated the outcome of our current policy of 90 days of CMV prophylaxis in seropositive recipients given ATG and the risk factors for the occurrence of CMV disease after prophylaxis. Methods We studied a retrospective cohort of 423 RTx (2010‐2014) CMV‐seropositive adults given ATG induction therapy. Results 54 (13%) patients developed CMV disease at a median of 163 days after transplant, of which 29 (54%) had viral syndrome and 25 (46%) had invasive disease. Median prophylaxis time (94 days) and immunosuppressive drugs were similar between groups (CMV vs no‐CMV). Those with CMV disease had more deceased donors and higher donor age, lower lymphocyte count, and lower median eGFR at day 90. Multivariable logistic regression analysis at day 90 and 180 found that eGFR ≤40 ml/min/1.73 m2 (but not acute rejection) was associated with late CMV disease. In a separate validation cohort of 124 patients with 8% late CMV disease, eGFR ≤45 and lymphocyte count ≤800 cells/mm3 at the end of prophylaxis remained predictive of late CMV disease occurrence. Conclusions These data indicate that antiviral prophylaxis adequately prevented CMV in seropositive recipients given ATG, but late disease still occurred. Low eGFR and low lymphocyte count at the end of prophylaxis may help identify patients at higher risk of CMV disease.
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F. ; Kotton, Camille N. ; David‐Neto, Elias</creator><creatorcontrib>Reusing, Jose O. ; Feitosa, Emanoela B. ; Agena, Fabiana ; Pierrotti, Lígia C. ; Azevedo, Luiz S. F. ; Kotton, Camille N. ; David‐Neto, Elias</creatorcontrib><description>Background Anti‐thymocyte globulin (ATG) therapy is a risk factor for cytomegalovirus (CMV) disease in renal transplant (RTx) recipients and therefore antiviral prophylaxis is commonly used. We evaluated the outcome of our current policy of 90 days of CMV prophylaxis in seropositive recipients given ATG and the risk factors for the occurrence of CMV disease after prophylaxis. Methods We studied a retrospective cohort of 423 RTx (2010‐2014) CMV‐seropositive adults given ATG induction therapy. Results 54 (13%) patients developed CMV disease at a median of 163 days after transplant, of which 29 (54%) had viral syndrome and 25 (46%) had invasive disease. Median prophylaxis time (94 days) and immunosuppressive drugs were similar between groups (CMV vs no‐CMV). Those with CMV disease had more deceased donors and higher donor age, lower lymphocyte count, and lower median eGFR at day 90. Multivariable logistic regression analysis at day 90 and 180 found that eGFR ≤40 ml/min/1.73 m2 (but not acute rejection) was associated with late CMV disease. In a separate validation cohort of 124 patients with 8% late CMV disease, eGFR ≤45 and lymphocyte count ≤800 cells/mm3 at the end of prophylaxis remained predictive of late CMV disease occurrence. Conclusions These data indicate that antiviral prophylaxis adequately prevented CMV in seropositive recipients given ATG, but late disease still occurred. Low eGFR and low lymphocyte count at the end of prophylaxis may help identify patients at higher risk of CMV disease.</description><identifier>ISSN: 1398-2273</identifier><identifier>EISSN: 1399-3062</identifier><identifier>DOI: 10.1111/tid.12929</identifier><identifier>PMID: 29809309</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Adult ; Adults ; Age Factors ; Antibiotic Prophylaxis - methods ; Antilymphocyte Serum - adverse effects ; Antiviral agents ; Antiviral Agents - therapeutic use ; Cell number ; Cytomegalovirus ; Cytomegalovirus - isolation &amp; purification ; cytomegalovirus disease ; Cytomegalovirus Infections - blood ; Cytomegalovirus Infections - epidemiology ; Cytomegalovirus Infections - prevention &amp; control ; Cytomegalovirus Infections - virology ; Epidermal growth factor receptors ; Female ; Globulins ; Glomerular Filtration Rate ; Graft rejection ; Graft Rejection - immunology ; Graft Rejection - prevention &amp; control ; Health risk assessment ; Humans ; Immunosuppressive agents ; Immunosuppressive Agents - adverse effects ; Induction therapy ; Kidney transplantation ; Kidney Transplantation - adverse effects ; Kidney transplants ; late CMV ; Lymphocyte Count ; Lymphocytes ; Male ; Middle Aged ; Patients ; Prophylaxis ; Regression analysis ; renal transplantation ; Retrospective Studies ; Risk analysis ; Risk Factors ; Serologic Tests ; Therapy ; Thymoglobulin ; Time Factors ; Transplant Recipients - statistics &amp; numerical data ; Treatment Outcome</subject><ispartof>Transplant infectious disease, 2018-10, Vol.20 (5), p.e12929-n/a</ispartof><rights>2018 John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd</rights><rights>2018 John Wiley &amp; Sons A/S. 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F.</creatorcontrib><creatorcontrib>Kotton, Camille N.</creatorcontrib><creatorcontrib>David‐Neto, Elias</creatorcontrib><title>Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: Outcome and risk factors for late CMV disease</title><title>Transplant infectious disease</title><addtitle>Transpl Infect Dis</addtitle><description>Background Anti‐thymocyte globulin (ATG) therapy is a risk factor for cytomegalovirus (CMV) disease in renal transplant (RTx) recipients and therefore antiviral prophylaxis is commonly used. We evaluated the outcome of our current policy of 90 days of CMV prophylaxis in seropositive recipients given ATG and the risk factors for the occurrence of CMV disease after prophylaxis. Methods We studied a retrospective cohort of 423 RTx (2010‐2014) CMV‐seropositive adults given ATG induction therapy. Results 54 (13%) patients developed CMV disease at a median of 163 days after transplant, of which 29 (54%) had viral syndrome and 25 (46%) had invasive disease. Median prophylaxis time (94 days) and immunosuppressive drugs were similar between groups (CMV vs no‐CMV). Those with CMV disease had more deceased donors and higher donor age, lower lymphocyte count, and lower median eGFR at day 90. Multivariable logistic regression analysis at day 90 and 180 found that eGFR ≤40 ml/min/1.73 m2 (but not acute rejection) was associated with late CMV disease. In a separate validation cohort of 124 patients with 8% late CMV disease, eGFR ≤45 and lymphocyte count ≤800 cells/mm3 at the end of prophylaxis remained predictive of late CMV disease occurrence. Conclusions These data indicate that antiviral prophylaxis adequately prevented CMV in seropositive recipients given ATG, but late disease still occurred. Low eGFR and low lymphocyte count at the end of prophylaxis may help identify patients at higher risk of CMV disease.</description><subject>Adult</subject><subject>Adults</subject><subject>Age Factors</subject><subject>Antibiotic Prophylaxis - methods</subject><subject>Antilymphocyte Serum - adverse effects</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Cell number</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus - isolation &amp; purification</subject><subject>cytomegalovirus disease</subject><subject>Cytomegalovirus Infections - blood</subject><subject>Cytomegalovirus Infections - epidemiology</subject><subject>Cytomegalovirus Infections - prevention &amp; control</subject><subject>Cytomegalovirus Infections - virology</subject><subject>Epidermal growth factor receptors</subject><subject>Female</subject><subject>Globulins</subject><subject>Glomerular Filtration Rate</subject><subject>Graft rejection</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - prevention &amp; control</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Immunosuppressive agents</subject><subject>Immunosuppressive Agents - adverse effects</subject><subject>Induction therapy</subject><subject>Kidney transplantation</subject><subject>Kidney Transplantation - adverse effects</subject><subject>Kidney transplants</subject><subject>late CMV</subject><subject>Lymphocyte Count</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Patients</subject><subject>Prophylaxis</subject><subject>Regression analysis</subject><subject>renal transplantation</subject><subject>Retrospective Studies</subject><subject>Risk analysis</subject><subject>Risk Factors</subject><subject>Serologic Tests</subject><subject>Therapy</subject><subject>Thymoglobulin</subject><subject>Time Factors</subject><subject>Transplant Recipients - statistics &amp; numerical data</subject><subject>Treatment Outcome</subject><issn>1398-2273</issn><issn>1399-3062</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctu1TAQhiMEoqWw4AWQJTawSOtLjmOzQ4dbpaJuCtto4supi2MH2zmQt-FRcXsKCyS88Xj06Rt5_qZ5TvApqeesOH1KqKTyQXNMmJQtw5w-vKtFS2nPjponOd9gTHrZycfNEZUCS4blcfNru5Y4mR34uHdpyWhOcb5ePfx0GbmAsqnvmF1xe4OSCeBRSRDy7CGU2lBudiaUfFsat3dhh8r1OsWdj-Piq8AFvajiYqh9k2Be36DLpag6E0HQKLn8DVlQJaaMbEzIQzFo-_kr0i4byOZp88iCz-bZ_X3SfPnw_mr7qb24_Hi-fXvRKrZhsrUC-l6NEo9jD5oz220k55qpjii1EVZrDkCFErIXjFs7CsElMAGWiNFsRnbSvDp46wK-LyaXYXJZGV__aeKSB4o7zjGTHanoy3_Qm7ikuppKEcIF6WnfVer1gVIp5pyMHebkJkjrQPBwG9tQYxvuYqvsi3vjMk5G_yX_5FSBswPww3mz_t80XJ2_Oyh_A7RRppU</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Reusing, Jose O.</creator><creator>Feitosa, Emanoela B.</creator><creator>Agena, Fabiana</creator><creator>Pierrotti, Lígia C.</creator><creator>Azevedo, Luiz S. 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F.</creatorcontrib><creatorcontrib>Kotton, Camille N.</creatorcontrib><creatorcontrib>David‐Neto, Elias</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transplant infectious disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reusing, Jose O.</au><au>Feitosa, Emanoela B.</au><au>Agena, Fabiana</au><au>Pierrotti, Lígia C.</au><au>Azevedo, Luiz S. F.</au><au>Kotton, Camille N.</au><au>David‐Neto, Elias</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: Outcome and risk factors for late CMV disease</atitle><jtitle>Transplant infectious disease</jtitle><addtitle>Transpl Infect Dis</addtitle><date>2018-10</date><risdate>2018</risdate><volume>20</volume><issue>5</issue><spage>e12929</spage><epage>n/a</epage><pages>e12929-n/a</pages><issn>1398-2273</issn><eissn>1399-3062</eissn><abstract>Background Anti‐thymocyte globulin (ATG) therapy is a risk factor for cytomegalovirus (CMV) disease in renal transplant (RTx) recipients and therefore antiviral prophylaxis is commonly used. We evaluated the outcome of our current policy of 90 days of CMV prophylaxis in seropositive recipients given ATG and the risk factors for the occurrence of CMV disease after prophylaxis. Methods We studied a retrospective cohort of 423 RTx (2010‐2014) CMV‐seropositive adults given ATG induction therapy. Results 54 (13%) patients developed CMV disease at a median of 163 days after transplant, of which 29 (54%) had viral syndrome and 25 (46%) had invasive disease. Median prophylaxis time (94 days) and immunosuppressive drugs were similar between groups (CMV vs no‐CMV). Those with CMV disease had more deceased donors and higher donor age, lower lymphocyte count, and lower median eGFR at day 90. Multivariable logistic regression analysis at day 90 and 180 found that eGFR ≤40 ml/min/1.73 m2 (but not acute rejection) was associated with late CMV disease. In a separate validation cohort of 124 patients with 8% late CMV disease, eGFR ≤45 and lymphocyte count ≤800 cells/mm3 at the end of prophylaxis remained predictive of late CMV disease occurrence. Conclusions These data indicate that antiviral prophylaxis adequately prevented CMV in seropositive recipients given ATG, but late disease still occurred. Low eGFR and low lymphocyte count at the end of prophylaxis may help identify patients at higher risk of CMV disease.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29809309</pmid><doi>10.1111/tid.12929</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9860-5339</orcidid></addata></record>
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source MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Adult
Adults
Age Factors
Antibiotic Prophylaxis - methods
Antilymphocyte Serum - adverse effects
Antiviral agents
Antiviral Agents - therapeutic use
Cell number
Cytomegalovirus
Cytomegalovirus - isolation & purification
cytomegalovirus disease
Cytomegalovirus Infections - blood
Cytomegalovirus Infections - epidemiology
Cytomegalovirus Infections - prevention & control
Cytomegalovirus Infections - virology
Epidermal growth factor receptors
Female
Globulins
Glomerular Filtration Rate
Graft rejection
Graft Rejection - immunology
Graft Rejection - prevention & control
Health risk assessment
Humans
Immunosuppressive agents
Immunosuppressive Agents - adverse effects
Induction therapy
Kidney transplantation
Kidney Transplantation - adverse effects
Kidney transplants
late CMV
Lymphocyte Count
Lymphocytes
Male
Middle Aged
Patients
Prophylaxis
Regression analysis
renal transplantation
Retrospective Studies
Risk analysis
Risk Factors
Serologic Tests
Therapy
Thymoglobulin
Time Factors
Transplant Recipients - statistics & numerical data
Treatment Outcome
title Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: Outcome and risk factors for late CMV disease
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