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 |
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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. |
doi_str_mv | 10.1111/tid.12929 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2046603941</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2116817274</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3539-f8a77cb90bb7ad63f45966d3c41cc58fdd6aa28c897836ffb8869a38af18be5b3</originalsourceid><addsrcrecordid>eNp1kctu1TAQhiMEoqWw4AWQJTawSOtLjmOzQ4dbpaJuCtto4supi2MH2zmQt-FRcXsKCyS88Xj06Rt5_qZ5TvApqeesOH1KqKTyQXNMmJQtw5w-vKtFS2nPjponOd9gTHrZycfNEZUCS4blcfNru5Y4mR34uHdpyWhOcb5ePfx0GbmAsqnvmF1xe4OSCeBRSRDy7CGU2lBudiaUfFsat3dhh8r1OsWdj-Piq8AFvajiYqh9k2Be36DLpag6E0HQKLn8DVlQJaaMbEzIQzFo-_kr0i4byOZp88iCz-bZ_X3SfPnw_mr7qb24_Hi-fXvRKrZhsrUC-l6NEo9jD5oz220k55qpjii1EVZrDkCFErIXjFs7CsElMAGWiNFsRnbSvDp46wK-LyaXYXJZGV__aeKSB4o7zjGTHanoy3_Qm7ikuppKEcIF6WnfVer1gVIp5pyMHebkJkjrQPBwG9tQYxvuYqvsi3vjMk5G_yX_5FSBswPww3mz_t80XJ2_Oyh_A7RRppU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2116817274</pqid></control><display><type>article</type><title>Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: Outcome and risk factors for late CMV disease</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Reusing, Jose O. ; Feitosa, Emanoela B. ; Agena, Fabiana ; Pierrotti, Lígia C. ; Azevedo, Luiz S. 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 & 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</subject><ispartof>Transplant infectious disease, 2018-10, Vol.20 (5), p.e12929-n/a</ispartof><rights>2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>2018 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3539-f8a77cb90bb7ad63f45966d3c41cc58fdd6aa28c897836ffb8869a38af18be5b3</citedby><cites>FETCH-LOGICAL-c3539-f8a77cb90bb7ad63f45966d3c41cc58fdd6aa28c897836ffb8869a38af18be5b3</cites><orcidid>0000-0001-9860-5339</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Ftid.12929$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Ftid.12929$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29809309$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reusing, Jose O.</creatorcontrib><creatorcontrib>Feitosa, Emanoela B.</creatorcontrib><creatorcontrib>Agena, Fabiana</creatorcontrib><creatorcontrib>Pierrotti, Lígia C.</creatorcontrib><creatorcontrib>Azevedo, Luiz S. 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 & purification</subject><subject>cytomegalovirus disease</subject><subject>Cytomegalovirus Infections - blood</subject><subject>Cytomegalovirus Infections - epidemiology</subject><subject>Cytomegalovirus Infections - prevention & 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 & 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 & 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. F.</creator><creator>Kotton, Camille N.</creator><creator>David‐Neto, Elias</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9860-5339</orcidid></search><sort><creationdate>201810</creationdate><title>Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: Outcome and risk factors for late CMV disease</title><author>Reusing, Jose O. ; Feitosa, Emanoela B. ; Agena, Fabiana ; Pierrotti, Lígia C. ; Azevedo, Luiz S. F. ; Kotton, Camille N. ; David‐Neto, Elias</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3539-f8a77cb90bb7ad63f45966d3c41cc58fdd6aa28c897836ffb8869a38af18be5b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Adults</topic><topic>Age Factors</topic><topic>Antibiotic Prophylaxis - methods</topic><topic>Antilymphocyte Serum - adverse effects</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Cell number</topic><topic>Cytomegalovirus</topic><topic>Cytomegalovirus - isolation & purification</topic><topic>cytomegalovirus disease</topic><topic>Cytomegalovirus Infections - blood</topic><topic>Cytomegalovirus Infections - epidemiology</topic><topic>Cytomegalovirus Infections - prevention & control</topic><topic>Cytomegalovirus Infections - virology</topic><topic>Epidermal growth factor receptors</topic><topic>Female</topic><topic>Globulins</topic><topic>Glomerular Filtration Rate</topic><topic>Graft rejection</topic><topic>Graft Rejection - immunology</topic><topic>Graft Rejection - prevention & control</topic><topic>Health risk assessment</topic><topic>Humans</topic><topic>Immunosuppressive agents</topic><topic>Immunosuppressive Agents - adverse effects</topic><topic>Induction therapy</topic><topic>Kidney transplantation</topic><topic>Kidney Transplantation - adverse effects</topic><topic>Kidney transplants</topic><topic>late CMV</topic><topic>Lymphocyte Count</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Patients</topic><topic>Prophylaxis</topic><topic>Regression analysis</topic><topic>renal transplantation</topic><topic>Retrospective Studies</topic><topic>Risk analysis</topic><topic>Risk Factors</topic><topic>Serologic Tests</topic><topic>Therapy</topic><topic>Thymoglobulin</topic><topic>Time Factors</topic><topic>Transplant Recipients - statistics & numerical data</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reusing, Jose O.</creatorcontrib><creatorcontrib>Feitosa, Emanoela B.</creatorcontrib><creatorcontrib>Agena, Fabiana</creatorcontrib><creatorcontrib>Pierrotti, Lígia C.</creatorcontrib><creatorcontrib>Azevedo, Luiz S. 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 & 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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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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