Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome—a single-centre experience and review of the literature
Identifieur interne : 001A86 ( Istex/Corpus ); précédent : 001A85; suivant : 001A87Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome—a single-centre experience and review of the literature
Auteurs : Stefan M. Weiner ; Lorenz Sellin ; Oliver Vonend ; Peter Schenker ; Nikolaus J. Buchner ; Markus Flecken ; Richard Viebahn ; Lars C. RumpSource :
- Nephrology Dialysis Transplantation [ 0931-0509 ] ; 2007-12.
Abstract
Background. The introduction of sirolimus as an immunosuppressive drug for renal transplantation has lead to an increase of unexplained interstitial pneumonitis. Methods. Out of a cohort of 115 patients receiving sirolimus for prophylaxis of renal and/or pancreas transplant rejection, 11 patients with interstitial pneumonitis were identified. Medical records and published case series were reviewed to identify risk factors associated with the occurrence of pneumonitis. Results. Eleven out of 80 patients (14%) with late switch to sirolimus developed pneumonitis, in contrast to none of the 35 patients with de novo use of sirolimus. The mean sirolimus trough level at presentation was 16.7 μg/l (range: 6.2–38.7 μg/l). Glomerular filtration rate (GFR) was significantly lower in patients with pneumonitis compared to controls (mean 21.3 ± 3.9 ml/min vs 38.65 ± 2.14 ml/min P = 0.002). Two patients needed haemodialysis shortly before pneumonitis was diagnosed. In a multivariate analysis only serum creatinine and GFR were independent predictors for pneumonitis. Sirolimus was discontinuated in five patients and the dose reduced in the other patients. Pneumonitis resolved within 14–28 days in all patients. One patient who had continued low-dose sirolimus treatment relapsed after 5 months, the other five patients had no relapse over a period of 15–48 months. Pooled analysis of our data and other published case series showed that the frequency of pneumonitis in patients with de novo use of sirolimus is significantly lower than in patients with late switch [5/133 (4%) vs 46/326 (14%) patients, P = 0.0024]. Conclusions. Late switch to sirolimus and impaired renal function are risk factors for pneumonitis. A sirolimus blood trough level above 12 μg/l may increase the risk, but pneumonitis may also occur at blood trough levels as low as 6 μg/l. Since pneumonitis may recur during low-dose sirolimus treatment, discontinuation of sirolimus appears to be the safest treatment option.
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DOI: 10.1093/ndt/gfm420
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Weiner</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: stefan.weiner@ruhr-uni-bochum.de</mods:affiliation></affiliation></author><author><name sortKey="Sellin, Lorenz" sort="Sellin, Lorenz" uniqKey="Sellin L" first="Lorenz" last="Sellin">Lorenz Sellin</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Vonend, Oliver" sort="Vonend, Oliver" uniqKey="Vonend O" first="Oliver" last="Vonend">Oliver Vonend</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Schenker, Peter" sort="Schenker, Peter" uniqKey="Schenker P" first="Peter" last="Schenker">Peter Schenker</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Buchner, Nikolaus J" sort="Buchner, Nikolaus J" uniqKey="Buchner N" first="Nikolaus J." last="Buchner">Nikolaus J. Buchner</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Flecken, Markus" sort="Flecken, Markus" uniqKey="Flecken M" first="Markus" last="Flecken">Markus Flecken</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Viebahn, Richard" sort="Viebahn, Richard" uniqKey="Viebahn R" first="Richard" last="Viebahn">Richard Viebahn</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Rump, Lars C" sort="Rump, Lars C" uniqKey="Rump L" first="Lars C." last="Rump">Lars C. Rump</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:4CE86746E82E638D86C03998FD14A619EA573E67</idno><date when="2007" year="2007">2007</date><idno type="doi">10.1093/ndt/gfm420</idno><idno type="url">https://api.istex.fr/document/4CE86746E82E638D86C03998FD14A619EA573E67/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001A86</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001A86</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome—a single-centre experience and review of the literature</title><author><name sortKey="Weiner, Stefan M" sort="Weiner, Stefan M" uniqKey="Weiner S" first="Stefan M." last="Weiner">Stefan M. Weiner</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: stefan.weiner@ruhr-uni-bochum.de</mods:affiliation></affiliation></author><author><name sortKey="Sellin, Lorenz" sort="Sellin, Lorenz" uniqKey="Sellin L" first="Lorenz" last="Sellin">Lorenz Sellin</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Vonend, Oliver" sort="Vonend, Oliver" uniqKey="Vonend O" first="Oliver" last="Vonend">Oliver Vonend</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Schenker, Peter" sort="Schenker, Peter" uniqKey="Schenker P" first="Peter" last="Schenker">Peter Schenker</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Buchner, Nikolaus J" sort="Buchner, Nikolaus J" uniqKey="Buchner N" first="Nikolaus J." last="Buchner">Nikolaus J. Buchner</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Flecken, Markus" sort="Flecken, Markus" uniqKey="Flecken M" first="Markus" last="Flecken">Markus Flecken</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Viebahn, Richard" sort="Viebahn, Richard" uniqKey="Viebahn R" first="Richard" last="Viebahn">Richard Viebahn</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Rump, Lars C" sort="Rump, Lars C" uniqKey="Rump L" first="Lars C." last="Rump">Lars C. Rump</name><affiliation><mods:affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Nephrology Dialysis Transplantation</title><idno type="ISSN">0931-0509</idno><idno type="eISSN">1460-2385</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2007-12">2007-12</date><biblScope unit="volume">22</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="3631">3631</biblScope><biblScope unit="page" to="3637">3637</biblScope></imprint><idno type="ISSN">0931-0509</idno></series><idno type="istex">4CE86746E82E638D86C03998FD14A619EA573E67</idno><idno type="DOI">10.1093/ndt/gfm420</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0931-0509</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Background. The introduction of sirolimus as an immunosuppressive drug for renal transplantation has lead to an increase of unexplained interstitial pneumonitis. Methods. Out of a cohort of 115 patients receiving sirolimus for prophylaxis of renal and/or pancreas transplant rejection, 11 patients with interstitial pneumonitis were identified. Medical records and published case series were reviewed to identify risk factors associated with the occurrence of pneumonitis. Results. Eleven out of 80 patients (14%) with late switch to sirolimus developed pneumonitis, in contrast to none of the 35 patients with de novo use of sirolimus. The mean sirolimus trough level at presentation was 16.7 μg/l (range: 6.2–38.7 μg/l). Glomerular filtration rate (GFR) was significantly lower in patients with pneumonitis compared to controls (mean 21.3 ± 3.9 ml/min vs 38.65 ± 2.14 ml/min P = 0.002). Two patients needed haemodialysis shortly before pneumonitis was diagnosed. In a multivariate analysis only serum creatinine and GFR were independent predictors for pneumonitis. Sirolimus was discontinuated in five patients and the dose reduced in the other patients. Pneumonitis resolved within 14–28 days in all patients. One patient who had continued low-dose sirolimus treatment relapsed after 5 months, the other five patients had no relapse over a period of 15–48 months. Pooled analysis of our data and other published case series showed that the frequency of pneumonitis in patients with de novo use of sirolimus is significantly lower than in patients with late switch [5/133 (4%) vs 46/326 (14%) patients, P = 0.0024]. Conclusions. Late switch to sirolimus and impaired renal function are risk factors for pneumonitis. A sirolimus blood trough level above 12 μg/l may increase the risk, but pneumonitis may also occur at blood trough levels as low as 6 μg/l. Since pneumonitis may recur during low-dose sirolimus treatment, discontinuation of sirolimus appears to be the safest treatment option.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Stefan M. Weiner</name><affiliations><json:string>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</json:string><json:string>E-mail: stefan.weiner@ruhr-uni-bochum.de</json:string></affiliations></json:item><json:item><name>Lorenz Sellin</name><affiliations><json:string>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</json:string></affiliations></json:item><json:item><name>Oliver Vonend</name><affiliations><json:string>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</json:string></affiliations></json:item><json:item><name>Peter Schenker</name><affiliations><json:string>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</json:string></affiliations></json:item><json:item><name>Nikolaus J. Buchner</name><affiliations><json:string>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</json:string></affiliations></json:item><json:item><name>Markus Flecken</name><affiliations><json:string>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</json:string></affiliations></json:item><json:item><name>Richard Viebahn</name><affiliations><json:string>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</json:string></affiliations></json:item><json:item><name>Lars C. Rump</name><affiliations><json:string>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</json:string></affiliations></json:item></author><subject><json:item><value>II. Scientific Papers</value></json:item><json:item><value>pancreas transplantation</value></json:item><json:item><value>pneumonitis</value></json:item><json:item><value>rapamycin</value></json:item><json:item><value>renal transplantation</value></json:item><json:item><value>risk factor</value></json:item><json:item><value>sirolimus</value></json:item></subject><language><json:string>unknown</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>Background. The introduction of sirolimus as an immunosuppressive drug for renal transplantation has lead to an increase of unexplained interstitial pneumonitis. Methods. Out of a cohort of 115 patients receiving sirolimus for prophylaxis of renal and/or pancreas transplant rejection, 11 patients with interstitial pneumonitis were identified. Medical records and published case series were reviewed to identify risk factors associated with the occurrence of pneumonitis. Results. Eleven out of 80 patients (14%) with late switch to sirolimus developed pneumonitis, in contrast to none of the 35 patients with de novo use of sirolimus. The mean sirolimus trough level at presentation was 16.7 μg/l (range: 6.2–38.7 μg/l). Glomerular filtration rate (GFR) was significantly lower in patients with pneumonitis compared to controls (mean 21.3 ± 3.9 ml/min vs 38.65 ± 2.14 ml/min P = 0.002). Two patients needed haemodialysis shortly before pneumonitis was diagnosed. In a multivariate analysis only serum creatinine and GFR were independent predictors for pneumonitis. Sirolimus was discontinuated in five patients and the dose reduced in the other patients. Pneumonitis resolved within 14–28 days in all patients. One patient who had continued low-dose sirolimus treatment relapsed after 5 months, the other five patients had no relapse over a period of 15–48 months. Pooled analysis of our data and other published case series showed that the frequency of pneumonitis in patients with de novo use of sirolimus is significantly lower than in patients with late switch [5/133 (4%) vs 46/326 (14%) patients, P = 0.0024]. Conclusions. Late switch to sirolimus and impaired renal function are risk factors for pneumonitis. A sirolimus blood trough level above 12 μg/l may increase the risk, but pneumonitis may also occur at blood trough levels as low as 6 μg/l. Since pneumonitis may recur during low-dose sirolimus treatment, discontinuation of sirolimus appears to be the safest treatment option.</abstract><qualityIndicators><score>8.342</score><pdfVersion>1.4</pdfVersion><pdfPageSize>612 x 791 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>7</keywordCount><abstractCharCount>1994</abstractCharCount><pdfWordCount>3342</pdfWordCount><pdfCharCount>22913</pdfCharCount><pdfPageCount>7</pdfPageCount><abstractWordCount>296</abstractWordCount></qualityIndicators><title>Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome—a single-centre experience and review of the literature</title><refBibs><json:item><author><json:item><name>PT Pham</name></json:item><json:item><name>PC Pham</name></json:item><json:item><name>GM 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management</title></json:item></refBibs><genre><json:string>research-article</json:string></genre><host><volume>22</volume><publisherId><json:string>ndt</json:string></publisherId><pages><last>3637</last><first>3631</first></pages><issn><json:string>0931-0509</json:string></issn><issue>12</issue><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-2385</json:string></eissn><title>Nephrology Dialysis Transplantation</title></host><categories><wos><json:string>science</json:string><json:string>urology & nephrology</json:string><json:string>transplantation</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>urology & nephrology</json:string></scienceMetrix></categories><publicationDate>2007</publicationDate><copyrightDate>2007</copyrightDate><doi><json:string>10.1093/ndt/gfm420</json:string></doi><id>4CE86746E82E638D86C03998FD14A619EA573E67</id><score>0.39886826</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/4CE86746E82E638D86C03998FD14A619EA573E67/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/4CE86746E82E638D86C03998FD14A619EA573E67/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/4CE86746E82E638D86C03998FD14A619EA573E67/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome—a single-centre experience and review of the literature</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><p>© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</p></availability><date>2007-07-04</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome—a single-centre experience and review of the literature</title><author xml:id="author-1" corresp="yes"><persName><forename type="first">Stefan M.</forename><surname>Weiner</surname></persName><email>stefan.weiner@ruhr-uni-bochum.de</email><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation></author><author xml:id="author-2"><persName><forename type="first">Lorenz</forename><surname>Sellin</surname></persName><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation></author><author xml:id="author-3"><persName><forename type="first">Oliver</forename><surname>Vonend</surname></persName><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation></author><author xml:id="author-4"><persName><forename type="first">Peter</forename><surname>Schenker</surname></persName><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation></author><author xml:id="author-5"><persName><forename type="first">Nikolaus J.</forename><surname>Buchner</surname></persName><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation></author><author xml:id="author-6"><persName><forename type="first">Markus</forename><surname>Flecken</surname></persName><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation></author><author xml:id="author-7"><persName><forename type="first">Richard</forename><surname>Viebahn</surname></persName><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation></author><author xml:id="author-8"><persName><forename type="first">Lars C.</forename><surname>Rump</surname></persName><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation></author></analytic><monogr><title level="j">Nephrology Dialysis Transplantation</title><idno type="pISSN">0931-0509</idno><idno type="eISSN">1460-2385</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2007-12"></date><biblScope unit="volume">22</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="3631">3631</biblScope><biblScope unit="page" to="3637">3637</biblScope></imprint></monogr><idno type="istex">4CE86746E82E638D86C03998FD14A619EA573E67</idno><idno type="DOI">10.1093/ndt/gfm420</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2007-07-04</date></creation><abstract><p>Background. The introduction of sirolimus as an immunosuppressive drug for renal transplantation has lead to an increase of unexplained interstitial pneumonitis. Methods. Out of a cohort of 115 patients receiving sirolimus for prophylaxis of renal and/or pancreas transplant rejection, 11 patients with interstitial pneumonitis were identified. Medical records and published case series were reviewed to identify risk factors associated with the occurrence of pneumonitis. Results. Eleven out of 80 patients (14%) with late switch to sirolimus developed pneumonitis, in contrast to none of the 35 patients with de novo use of sirolimus. The mean sirolimus trough level at presentation was 16.7 μg/l (range: 6.2–38.7 μg/l). Glomerular filtration rate (GFR) was significantly lower in patients with pneumonitis compared to controls (mean 21.3 ± 3.9 ml/min vs 38.65 ± 2.14 ml/min P = 0.002). Two patients needed haemodialysis shortly before pneumonitis was diagnosed. In a multivariate analysis only serum creatinine and GFR were independent predictors for pneumonitis. Sirolimus was discontinuated in five patients and the dose reduced in the other patients. Pneumonitis resolved within 14–28 days in all patients. One patient who had continued low-dose sirolimus treatment relapsed after 5 months, the other five patients had no relapse over a period of 15–48 months. Pooled analysis of our data and other published case series showed that the frequency of pneumonitis in patients with de novo use of sirolimus is significantly lower than in patients with late switch [5/133 (4%) vs 46/326 (14%) patients, P = 0.0024]. Conclusions. Late switch to sirolimus and impaired renal function are risk factors for pneumonitis. A sirolimus blood trough level above 12 μg/l may increase the risk, but pneumonitis may also occur at blood trough levels as low as 6 μg/l. Since pneumonitis may recur during low-dose sirolimus treatment, discontinuation of sirolimus appears to be the safest treatment option.</p></abstract><textClass><keywords scheme="keyword"><list><item><term>II. Scientific Papers</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>keywords</head><item><term>pancreas transplantation</term></item><item><term>pneumonitis</term></item><item><term>rapamycin</term></item><item><term>renal transplantation</term></item><item><term>risk factor</term></item><item><term>sirolimus</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2007-07-04">Created</change><change when="2007-12">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/4CE86746E82E638D86C03998FD14A619EA573E67/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="publisher-id">ndt</journal-id><journal-id journal-id-type="hwp">ndt</journal-id><journal-title>Nephrology Dialysis Transplantation</journal-title><issn pub-type="ppub">0931-0509</issn><issn pub-type="epub">1460-2385</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/ndt/gfm420</article-id><article-categories><subj-group><subject>II. Scientific Papers</subject><subj-group><subject>Original Articles: Dialysis and Transplantation</subject></subj-group></subj-group></article-categories><title-group><article-title>Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome—a single-centre experience and review of the literature</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Weiner</surname><given-names>Stefan M.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF1"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sellin</surname><given-names>Lorenz</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vonend</surname><given-names>Oliver</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Schenker</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="AFF1"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Buchner</surname><given-names>Nikolaus J.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Flecken</surname><given-names>Markus</given-names></name><xref ref-type="aff" rid="AFF1"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Viebahn</surname><given-names>Richard</given-names></name><xref ref-type="aff" rid="AFF1"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rump</surname><given-names>Lars C.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib></contrib-group><aff id="AFF1"><sup>1</sup>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, <sup>2</sup>Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and <sup>3</sup>Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</aff><author-notes><corresp><italic>Correspondence and offprint requests to:</italic> Stefan M. Weiner, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Nordallee 1, D-54292 Trier, Germany. Email: <email>stefan.weiner@ruhr-uni-bochum.de</email></corresp></author-notes><pub-date pub-type="ppub"><month>12</month><year>2007</year></pub-date><pub-date pub-type="epub"><day>4</day><month>7</month><year>2007</year></pub-date><volume>22</volume><issue>12</issue><fpage>3631</fpage><lpage>3637</lpage><history><date date-type="received"><day>10</day><month>12</month><year>2006</year></date><date date-type="accepted"><day>4</day><month>6</month><year>2007</year></date></history><copyright-statement>© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</copyright-statement><copyright-year>2007</copyright-year><abstract><p><bold>Background.</bold> The introduction of sirolimus as an immunosuppressive drug for renal transplantation has lead to an increase of unexplained interstitial pneumonitis.</p><p><bold>Methods.</bold> Out of a cohort of 115 patients receiving sirolimus for prophylaxis of renal and/or pancreas transplant rejection, 11 patients with interstitial pneumonitis were identified. Medical records and published case series were reviewed to identify risk factors associated with the occurrence of pneumonitis.</p><p><bold>Results.</bold> Eleven out of 80 patients (14%) with late switch to sirolimus developed pneumonitis, in contrast to none of the 35 patients with <italic>de novo</italic> use of sirolimus. The mean sirolimus trough level at presentation was 16.7 μg/l (range: 6.2–38.7 μg/l). Glomerular filtration rate (GFR) was significantly lower in patients with pneumonitis compared to controls (mean 21.3 ± 3.9 ml/min <italic>vs</italic> 38.65 ± 2.14 ml/min <italic>P</italic> = 0.002). Two patients needed haemodialysis shortly before pneumonitis was diagnosed. In a multivariate analysis only serum creatinine and GFR were independent predictors for pneumonitis.</p><p>Sirolimus was discontinuated in five patients and the dose reduced in the other patients. Pneumonitis resolved within 14–28 days in all patients. One patient who had continued low-dose sirolimus treatment relapsed after 5 months, the other five patients had no relapse over a period of 15–48 months.</p><p>Pooled analysis of our data and other published case series showed that the frequency of pneumonitis in patients with <italic>de novo</italic> use of sirolimus is significantly lower than in patients with late switch [5/133 (4%) <italic>vs</italic> 46/326 (14%) patients, <italic>P</italic> = 0.0024].</p><p><bold>Conclusions.</bold> Late switch to sirolimus and impaired renal function are risk factors for pneumonitis. A sirolimus blood trough level above 12 μg/l may increase the risk, but pneumonitis may also occur at blood trough levels as low as 6 μg/l. Since pneumonitis may recur during low-dose sirolimus treatment, discontinuation of sirolimus appears to be the safest treatment option.</p></abstract><kwd-group><kwd>pancreas transplantation</kwd><kwd>pneumonitis</kwd><kwd>rapamycin</kwd><kwd>renal transplantation</kwd><kwd>risk factor</kwd><kwd>sirolimus</kwd></kwd-group></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome—a single-centre experience and review of the literature</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome—a single-centre experience and review of the literature</title></titleInfo><name type="personal" displayLabel="corresp"><namePart type="given">Stefan M.</namePart><namePart type="family">Weiner</namePart><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation><affiliation>E-mail: stefan.weiner@ruhr-uni-bochum.de</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lorenz</namePart><namePart type="family">Sellin</namePart><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Oliver</namePart><namePart type="family">Vonend</namePart><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter</namePart><namePart type="family">Schenker</namePart><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nikolaus J.</namePart><namePart type="family">Buchner</namePart><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Markus</namePart><namePart type="family">Flecken</namePart><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Richard</namePart><namePart type="family">Viebahn</namePart><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lars C.</namePart><namePart type="family">Rump</namePart><affiliation>Department of Nephrology, Marienhospital Herne, Hospital of the Ruhr-University of Bochum, Hölkeskampring 40, 44625 Herne, Department of Nephrology, Krankenhaus der Barmherzigen Brüder Trier, Academic Clinic of the University of Mainz, Nordallee 1, 54292 Trier and Chirurgische Klinik, Knappschaftskrankenhaus, Hospital of the Ruhr-University of Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><subject><topic>II. Scientific Papers</topic></subject><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2007-12</dateIssued><dateCreated encoding="w3cdtf">2007-07-04</dateCreated><copyrightDate encoding="w3cdtf">2007</copyrightDate></originInfo><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>Background. The introduction of sirolimus as an immunosuppressive drug for renal transplantation has lead to an increase of unexplained interstitial pneumonitis. Methods. Out of a cohort of 115 patients receiving sirolimus for prophylaxis of renal and/or pancreas transplant rejection, 11 patients with interstitial pneumonitis were identified. Medical records and published case series were reviewed to identify risk factors associated with the occurrence of pneumonitis. Results. Eleven out of 80 patients (14%) with late switch to sirolimus developed pneumonitis, in contrast to none of the 35 patients with de novo use of sirolimus. The mean sirolimus trough level at presentation was 16.7 μg/l (range: 6.2–38.7 μg/l). Glomerular filtration rate (GFR) was significantly lower in patients with pneumonitis compared to controls (mean 21.3 ± 3.9 ml/min vs 38.65 ± 2.14 ml/min P = 0.002). Two patients needed haemodialysis shortly before pneumonitis was diagnosed. In a multivariate analysis only serum creatinine and GFR were independent predictors for pneumonitis. Sirolimus was discontinuated in five patients and the dose reduced in the other patients. Pneumonitis resolved within 14–28 days in all patients. One patient who had continued low-dose sirolimus treatment relapsed after 5 months, the other five patients had no relapse over a period of 15–48 months. Pooled analysis of our data and other published case series showed that the frequency of pneumonitis in patients with de novo use of sirolimus is significantly lower than in patients with late switch [5/133 (4%) vs 46/326 (14%) patients, P = 0.0024]. Conclusions. Late switch to sirolimus and impaired renal function are risk factors for pneumonitis. A sirolimus blood trough level above 12 μg/l may increase the risk, but pneumonitis may also occur at blood trough levels as low as 6 μg/l. Since pneumonitis may recur during low-dose sirolimus treatment, discontinuation of sirolimus appears to be the safest treatment option.</abstract><subject><genre>keywords</genre><topic>pancreas transplantation</topic><topic>pneumonitis</topic><topic>rapamycin</topic><topic>renal transplantation</topic><topic>risk factor</topic><topic>sirolimus</topic></subject><relatedItem type="host"><titleInfo><title>Nephrology Dialysis Transplantation</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0931-0509</identifier><identifier type="eISSN">1460-2385</identifier><identifier type="PublisherID">ndt</identifier><identifier type="PublisherID-hwp">ndt</identifier><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>22</number></detail><detail type="issue"><caption>no.</caption><number>12</number></detail><extent unit="pages"><start>3631</start><end>3637</end></extent></part></relatedItem><identifier type="istex">4CE86746E82E638D86C03998FD14A619EA573E67</identifier><identifier type="DOI">10.1093/ndt/gfm420</identifier><accessCondition type="use and reproduction" contentType="copyright">© The Author [2007]. 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