Oedema, solid organ transplantation and mammalian target of rapamycin inhibitor/proliferation signal inhibitors (mTOR-I/PSIs)
Identifieur interne : 000507 ( Pmc/Corpus ); précédent : 000506; suivant : 000508Oedema, solid organ transplantation and mammalian target of rapamycin inhibitor/proliferation signal inhibitors (mTOR-I/PSIs)
Auteurs : Chems Gharbi ; Victor Gueutin ; Hassan IzzedineSource :
- Clinical Kidney Journal [ 2048-8505 ] ; 2014.
Abstract
Mammalian target of rapamycin inhibitor (mTOR-I)/proliferation signal inhibitors (PSI) including sirolimus and everolimus represent a new class of drugs increasingly used in solid-organ transplantation as alternatives to calcineurin inhibitors for patients with renal dysfunction, transplant coronary arterial vasculopathy or malignancy. The most frequently occurring mTOR-I/PSI-related adverse events are similar to those associated with other immunosuppressive therapies, but some side effects are more characteristic of proliferation signal inhibitors (e.g. lymphocele, arthralgia, oedema and hyperlipidaemia). The present paper review incidence, clinical presentation and mechanism of oedema within the clinical experience of mTOR-I/PSI in solid organ transplantation.
Url:
DOI: 10.1093/ckj/sfu001
PubMed: 25852858
PubMed Central: 4377777
Links to Exploration step
PMC:4377777Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Oedema, solid organ transplantation and mammalian target of rapamycin inhibitor/proliferation signal inhibitors (mTOR-I/PSIs)</title><author><name sortKey="Gharbi, Chems" sort="Gharbi, Chems" uniqKey="Gharbi C" first="Chems" last="Gharbi">Chems Gharbi</name></author><author><name sortKey="Gueutin, Victor" sort="Gueutin, Victor" uniqKey="Gueutin V" first="Victor" last="Gueutin">Victor Gueutin</name></author><author><name sortKey="Izzedine, Hassan" sort="Izzedine, Hassan" uniqKey="Izzedine H" first="Hassan" last="Izzedine">Hassan Izzedine</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25852858</idno><idno type="pmc">4377777</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377777</idno><idno type="RBID">PMC:4377777</idno><idno type="doi">10.1093/ckj/sfu001</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000507</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000507</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Oedema, solid organ transplantation and mammalian target of rapamycin inhibitor/proliferation signal inhibitors (mTOR-I/PSIs)</title><author><name sortKey="Gharbi, Chems" sort="Gharbi, Chems" uniqKey="Gharbi C" first="Chems" last="Gharbi">Chems Gharbi</name></author><author><name sortKey="Gueutin, Victor" sort="Gueutin, Victor" uniqKey="Gueutin V" first="Victor" last="Gueutin">Victor Gueutin</name></author><author><name sortKey="Izzedine, Hassan" sort="Izzedine, Hassan" uniqKey="Izzedine H" first="Hassan" last="Izzedine">Hassan Izzedine</name></author></analytic><series><title level="j">Clinical Kidney Journal</title><idno type="ISSN">2048-8505</idno><idno type="eISSN">2048-8513</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Mammalian target of rapamycin inhibitor (mTOR-I)/proliferation signal inhibitors (PSI) including sirolimus and everolimus represent a new class of drugs increasingly used in solid-organ transplantation as alternatives to calcineurin inhibitors for patients with renal dysfunction, transplant coronary arterial vasculopathy or malignancy. The most frequently occurring mTOR-I/PSI-related adverse events are similar to those associated with other immunosuppressive therapies, but some side effects are more characteristic of proliferation signal inhibitors (e.g. lymphocele, arthralgia, oedema and hyperlipidaemia). The present paper review incidence, clinical presentation and mechanism of oedema within the clinical experience of mTOR-I/PSI in solid organ transplantation.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Valantine, H" uniqKey="Valantine H">H Valantine</name></author><author><name sortKey="Zuckermann, A" uniqKey="Zuckermann A">A Zuckermann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rostaing, L" uniqKey="Rostaing L">L Rostaing</name></author><author><name sortKey="Kamar, N" uniqKey="Kamar N">N Kamar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lehmkuhl, H" uniqKey="Lehmkuhl H">H Lehmkuhl</name></author><author><name sortKey="Ross, H" uniqKey="Ross H">H Ross</name></author><author><name sortKey="Arizon, J" uniqKey="Arizon J">J Arizon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gullestad, L" uniqKey="Gullestad L">L Gullestad</name></author><author><name sortKey="Iversen, M" uniqKey="Iversen M">M Iversen</name></author><author><name sortKey="Mortensen, Sa" uniqKey="Mortensen S">SA Mortensen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gullestad, L" uniqKey="Gullestad L">L Gullestad</name></author><author><name sortKey="Mortensen, Sa" uniqKey="Mortensen S">SA Mortensen</name></author><author><name sortKey="Eiskj R, H" uniqKey="Eiskj R H">H Eiskjær</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roman, A" uniqKey="Roman A">A Roman</name></author><author><name sortKey="Ussetti, P" uniqKey="Ussetti P">P Ussetti</name></author><author><name sortKey="Zurbano, F" uniqKey="Zurbano F">F Zurbano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Simone, P" uniqKey="De Simone P">P De Simone</name></author><author><name sortKey="Metselaar, Hj" uniqKey="Metselaar H">HJ Metselaar</name></author><author><name sortKey="Fischer, L" uniqKey="Fischer L">L Fischer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alegre, C" uniqKey="Alegre C">C Alegre</name></author><author><name sortKey="Jimenez, C" uniqKey="Jimenez C">C Jiménez</name></author><author><name sortKey="Manrique, A" uniqKey="Manrique A">A Manrique</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saliba, F" uniqKey="Saliba F">F Saliba</name></author><author><name sortKey="De Simone, P" uniqKey="De Simone P">P De Simone</name></author><author><name sortKey="Nevens, F" uniqKey="Nevens F">F Nevens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lorber, Mi" uniqKey="Lorber M">MI Lorber</name></author><author><name sortKey="Mulgaonkar, S" uniqKey="Mulgaonkar S">S Mulgaonkar</name></author><author><name sortKey="Butt, Km" uniqKey="Butt K">KM Butt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cotovio, P" uniqKey="Cotovio P">P Cotovio</name></author><author><name sortKey="Neves, M" uniqKey="Neves M">M Neves</name></author><author><name sortKey="Santos, L" uniqKey="Santos L">L Santos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shihab, Fs" uniqKey="Shihab F">FS Shihab</name></author><author><name sortKey="Cibrik, D" uniqKey="Cibrik D">D Cibrik</name></author><author><name sortKey="Chan, L" uniqKey="Chan L">L Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takahashi, K" uniqKey="Takahashi K">K Takahashi</name></author><author><name sortKey="Uchida, K" uniqKey="Uchida K">K Uchida</name></author><author><name sortKey="Yoshimura, N" uniqKey="Yoshimura N">N Yoshimura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moro, Ja" uniqKey="Moro J">JA Moro</name></author><author><name sortKey="Almenar, L" uniqKey="Almenar L">L Almenar</name></author><author><name sortKey="Martinez Dolz, L" uniqKey="Martinez Dolz L">L Martínez-Dolz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fukushima, N" uniqKey="Fukushima N">N Fukushima</name></author><author><name sortKey="Saito, S" uniqKey="Saito S">S Saito</name></author><author><name sortKey="Sakata, Y" uniqKey="Sakata Y">Y Sakata</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ersoy, A" uniqKey="Ersoy A">A Ersoy</name></author><author><name sortKey="Koca, N" uniqKey="Koca N">N Koca</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fuchs, U" uniqKey="Fuchs U">U Fuchs</name></author><author><name sortKey="Zittermann, A" uniqKey="Zittermann A">A Zittermann</name></author><author><name sortKey="Berthold, Hk" uniqKey="Berthold H">HK Berthold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aboujaoude, W" uniqKey="Aboujaoude W">W Aboujaoude</name></author><author><name sortKey="Milgrom, Ml" uniqKey="Milgrom M">ML Milgrom</name></author><author><name sortKey="Govani, Mv" uniqKey="Govani M">MV Govani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Romagnoli, J" uniqKey="Romagnoli J">J Romagnoli</name></author><author><name sortKey="Citterio, F" uniqKey="Citterio F">F Citterio</name></author><author><name sortKey="Nanni, G" uniqKey="Nanni G">G Nanni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Otaibi, T" uniqKey="Al Otaibi T">T Al-Otaibi</name></author><author><name sortKey="Ahamed, N" uniqKey="Ahamed N">N Ahamed</name></author><author><name sortKey="Nampoory, Mr" uniqKey="Nampoory M">MR Nampoory</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Bartolomeis, C" uniqKey="De Bartolomeis C">C De Bartolomeis</name></author><author><name sortKey="Collini, A" uniqKey="Collini A">A Collini</name></author><author><name sortKey="Rumberger, B" uniqKey="Rumberger B">B Rumberger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wadei, H" uniqKey="Wadei H">H Wadei</name></author><author><name sortKey="Gruber, Sa" uniqKey="Gruber S">SA Gruber</name></author><author><name sortKey="El Amm, Jm" uniqKey="El Amm J">JM El-Amm</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mohaupt, Mg" uniqKey="Mohaupt M">MG Mohaupt</name></author><author><name sortKey="Vogt, B" uniqKey="Vogt B">B Vogt</name></author><author><name sortKey="Frey, Fj" uniqKey="Frey F">FJ Frey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Papali, A" uniqKey="Papali A">A Papali</name></author><author><name sortKey="Giannetti, N" uniqKey="Giannetti N">N Giannetti</name></author><author><name sortKey="Cantarovich, M" uniqKey="Cantarovich M">M Cantarovich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amante, Aj" uniqKey="Amante A">AJ Amante</name></author><author><name sortKey="Kahan, Bd" uniqKey="Kahan B">BD Kahan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khauli, Rb" uniqKey="Khauli R">RB Khauli</name></author><author><name sortKey="Stoff, Js" uniqKey="Stoff J">JS Stoff</name></author><author><name sortKey="Lovewell, T" uniqKey="Lovewell T">T Lovewell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Malovrh, M" uniqKey="Malovrh M">M Malovrh</name></author><author><name sortKey="Kandus, A" uniqKey="Kandus A">A Kandus</name></author><author><name sortKey="Buturovic Ponikvar, J" uniqKey="Buturovic Ponikvar J">J Buturovic-Ponikvar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bry, J" uniqKey="Bry J">J Bry</name></author><author><name sortKey="Hull, D" uniqKey="Hull D">D Hull</name></author><author><name sortKey="Bartus, Sa" uniqKey="Bartus S">SA Bartus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schweizer, Rt" uniqKey="Schweizer R">RT Schweizer</name></author><author><name sortKey="Cho, S" uniqKey="Cho S">S Cho</name></author><author><name sortKey="Koutz, Sl" uniqKey="Koutz S">SL Koutz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Braun, We" uniqKey="Braun W">WE Braun</name></author><author><name sortKey="Banowsky, Lh" uniqKey="Banowsky L">LH Banowsky</name></author><author><name sortKey="Straffon, Ra" uniqKey="Straffon R">RA Straffon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zincke, H" uniqKey="Zincke H">H Zincke</name></author><author><name sortKey="Woods, Je" uniqKey="Woods J">JE Woods</name></author><author><name sortKey="Leary, Fj" uniqKey="Leary F">FJ Leary</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pollak, R" uniqKey="Pollak R">R Pollak</name></author><author><name sortKey="Veremis, Sa" uniqKey="Veremis S">SA Veremis</name></author><author><name sortKey="Maddux, Ms" uniqKey="Maddux M">MS Maddux</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vitko, S" uniqKey="Vitko S">S Vitko</name></author><author><name sortKey="Tedesco, H" uniqKey="Tedesco H">H Tedesco</name></author><author><name sortKey="Eris, J" uniqKey="Eris J">J Eris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kahan, Bd" uniqKey="Kahan B">BD Kahan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sansalone, Cv" uniqKey="Sansalone C">CV Sansalone</name></author><author><name sortKey="Aseni, P" uniqKey="Aseni P">P Aseni</name></author><author><name sortKey="Minetti, E" uniqKey="Minetti E">E Minetti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kay, R" uniqKey="Kay R">R Kay</name></author><author><name sortKey="Fuchs, E" uniqKey="Fuchs E">E Fuchs</name></author><author><name sortKey="Barry, Jm" uniqKey="Barry J">JM Barry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rashid, A" uniqKey="Rashid A">A Rashid</name></author><author><name sortKey="Posen, G" uniqKey="Posen G">G Posen</name></author><author><name sortKey="Couture, R" uniqKey="Couture R">R Couture</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bischof, G" uniqKey="Bischof G">G Bischof</name></author><author><name sortKey="Rockenschaub, S" uniqKey="Rockenschaub S">S Rockenschaub</name></author><author><name sortKey="Berlakovich, G" uniqKey="Berlakovich G">G Berlakovich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stephanian, E" uniqKey="Stephanian E">E Stephanian</name></author><author><name sortKey="Matas, Aj" uniqKey="Matas A">AJ Matas</name></author><author><name sortKey="Gores, P" uniqKey="Gores P">P Gores</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martinez Ocana, Jc" uniqKey="Martinez Ocana J">JC Martinez-Ocana</name></author><author><name sortKey="Lauzurica, R" uniqKey="Lauzurica R">R Lauzurica</name></author><author><name sortKey="Castellote, E" uniqKey="Castellote E">E Castellote</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Teruel, Jl" uniqKey="Teruel J">JL Teruel</name></author><author><name sortKey="Escobar, Em" uniqKey="Escobar E">EM Escobar</name></author><author><name sortKey="Quereda, C" uniqKey="Quereda C">C Quereda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Langer, Rm" uniqKey="Langer R">RM Langer</name></author><author><name sortKey="Kahan, Bd" uniqKey="Kahan B">BD Kahan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pascual, J" uniqKey="Pascual J">J Pascual</name></author><author><name sortKey="Marcen, R" uniqKey="Marcen R">R Marcén</name></author><author><name sortKey="Ortu O, J" uniqKey="Ortu O J">J Ortuño</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Greager, Ma" uniqKey="Greager M">MA Greager</name></author><author><name sortKey="Dzay" uniqKey="Dzay">Dzay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stoeltzing, O" uniqKey="Stoeltzing O">O Stoeltzing</name></author><author><name sortKey="Meric Bernstam, F" uniqKey="Meric Bernstam F">F Meric-Bernstam</name></author><author><name sortKey="Ellis, Lm" uniqKey="Ellis L">LM Ellis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karkkainen, Mj" uniqKey="Karkkainen M">MJ Karkkainen</name></author><author><name sortKey="Ferrell, Re" uniqKey="Ferrell R">RE Ferrell</name></author><author><name sortKey="Lawrence, Ec" uniqKey="Lawrence E">EC Lawrence</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="M Kinen, T" uniqKey="M Kinen T">T Mäkinen</name></author><author><name sortKey="Jussila, L" uniqKey="Jussila L">L Jussila</name></author><author><name sortKey="Veikkola, T" uniqKey="Veikkola T">T Veikkola</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huber, S" uniqKey="Huber S">S Huber</name></author><author><name sortKey="Bruns, Cj" uniqKey="Bruns C">CJ Bruns</name></author><author><name sortKey="Schmid, G" uniqKey="Schmid G">G Schmid</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Keogh, A" uniqKey="Keogh A">A Keogh</name></author><author><name sortKey="Richardson, M" uniqKey="Richardson M">M Richardson</name></author><author><name sortKey="Ruygrok, P" uniqKey="Ruygrok P">P Ruygrok</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Steele, Gh" uniqKey="Steele G">GH Steele</name></author><author><name sortKey="Adamkovic, Ab" uniqKey="Adamkovic A">AB Adamkovic</name></author><author><name sortKey="Demopoulos, La" uniqKey="Demopoulos L">LA Demopoulos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bouzas Mosquera, A" uniqKey="Bouzas Mosquera A">A Bouzas-Mosquera</name></author><author><name sortKey="Crespo Leiro, Mg" uniqKey="Crespo Leiro M">MG Crespo-Leiro</name></author><author><name sortKey="Paniagua, Mj" uniqKey="Paniagua M">MJ Paniagua</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agostoni, A" uniqKey="Agostoni A">A Agostoni</name></author><author><name sortKey="Cicardi, M" uniqKey="Cicardi M">M Cicardi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Israili, Zh" uniqKey="Israili Z">ZH Israili</name></author><author><name sortKey="Hall, Wd" uniqKey="Hall W">WD Hall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abbosh, J" uniqKey="Abbosh J">J Abbosh</name></author><author><name sortKey="Anderson, Ja" uniqKey="Anderson J">JA Anderson</name></author><author><name sortKey="Levine, Ab" uniqKey="Levine A">AB Levine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lykavieris, P" uniqKey="Lykavieris P">P Lykavieris</name></author><author><name sortKey="Frauger, E" uniqKey="Frauger E">E Frauger</name></author><author><name sortKey="Habes, D" uniqKey="Habes D">D Habes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Burdese, M" uniqKey="Burdese M">M Burdese</name></author><author><name sortKey="Rossetti, M" uniqKey="Rossetti M">M Rossetti</name></author><author><name sortKey="Guarena, C" uniqKey="Guarena C">C Guarena</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stallone, G" uniqKey="Stallone G">G Stallone</name></author><author><name sortKey="Infante, B" uniqKey="Infante B">B Infante</name></author><author><name sortKey="Di Paolo, S" uniqKey="Di Paolo S">S Di Paolo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Montalbano, M" uniqKey="Montalbano M">M Montalbano</name></author><author><name sortKey="Neff, Gw" uniqKey="Neff G">GW Neff</name></author><author><name sortKey="Yamashiki, N" uniqKey="Yamashiki N">N Yamashiki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mahe, E" uniqKey="Mahe E">E Mahé</name></author><author><name sortKey="Morelon, E" uniqKey="Morelon E">E Morelon</name></author><author><name sortKey="Lechaton, S" uniqKey="Lechaton S">S Lechaton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Krikorian, Rk" uniqKey="Krikorian R">RK Krikorian</name></author><author><name sortKey="Quick, A" uniqKey="Quick A">A Quick</name></author><author><name sortKey="Tal, A" uniqKey="Tal A">A Tal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gainer, Jv" uniqKey="Gainer J">JV Gainer</name></author><author><name sortKey="Nadeau, Jh" uniqKey="Nadeau J">JH Nadeau</name></author><author><name sortKey="Ryder, D" uniqKey="Ryder D">D Ryder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morimoto, T" uniqKey="Morimoto T">T Morimoto</name></author><author><name sortKey="Gandhi, Tk" uniqKey="Gandhi T">TK Gandhi</name></author><author><name sortKey="Fiskio, Jm" uniqKey="Fiskio J">JM Fiskio</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Flockhart, Da" uniqKey="Flockhart D">DA Flockhart</name></author><author><name sortKey="Tanus Santos, Je" uniqKey="Tanus Santos J">JE Tanus-Santos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lemahieu, Wp" uniqKey="Lemahieu W">WP Lemahieu</name></author><author><name sortKey="Maes, Bd" uniqKey="Maes B">BD Maes</name></author><author><name sortKey="Verbeke, K" uniqKey="Verbeke K">K Verbeke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barshes, Nr" uniqKey="Barshes N">NR Barshes</name></author><author><name sortKey="Goodpastor, Se" uniqKey="Goodpastor S">SE Goodpastor</name></author><author><name sortKey="Goss, Ja" uniqKey="Goss J">JA Goss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jeanmart, H" uniqKey="Jeanmart H">H Jeanmart</name></author><author><name sortKey="Malo, O" uniqKey="Malo O">O Malo</name></author><author><name sortKey="Carrier, M" uniqKey="Carrier M">M Carrier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mahe, E" uniqKey="Mahe E">E Mahé</name></author><author><name sortKey="Morelon, E" uniqKey="Morelon E">E Morelon</name></author><author><name sortKey="Lechaton, S" uniqKey="Lechaton S">S Lechaton</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Clin Kidney J</journal-id><journal-id journal-id-type="iso-abbrev">Clin Kidney J</journal-id><journal-id journal-id-type="publisher-id">ckj</journal-id><journal-id journal-id-type="hwp">ndtplus</journal-id><journal-title-group><journal-title>Clinical Kidney Journal</journal-title></journal-title-group><issn pub-type="ppub">2048-8505</issn><issn pub-type="epub">2048-8513</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25852858</article-id><article-id pub-id-type="pmc">4377777</article-id><article-id pub-id-type="doi">10.1093/ckj/sfu001</article-id><article-id pub-id-type="publisher-id">sfu001</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Contributions</subject><subj-group subj-group-type="heading"><subject>Minireviews</subject></subj-group></subj-group></article-categories><title-group><article-title>Oedema, solid organ transplantation and mammalian target of rapamycin inhibitor/proliferation signal inhibitors (mTOR-I/PSIs)</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Gharbi</surname><given-names>Chems</given-names></name></contrib><contrib contrib-type="author"><name><surname>Gueutin</surname><given-names>Victor</given-names></name></contrib><contrib contrib-type="author"><name><surname>Izzedine</surname><given-names>Hassan</given-names></name><xref ref-type="corresp" rid="cor1"></xref></contrib><aff><addr-line>Department of Nephrology</addr-line>,<institution>Pitié Salpetriere Hospital</institution>,<addr-line>Paris</addr-line>,<country>France</country></aff></contrib-group><author-notes><corresp id="cor1"><italic>Correspondence and offprint requests to:</italic> Hassan Izzedine; E-mail: <email>hassan.izzedine@psl.aphp.fr</email></corresp></author-notes><pub-date pub-type="ppub"><month>4</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>24</day><month>2</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>24</day><month>2</month><year>2014</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>7</volume><issue>2</issue><fpage>115</fpage><lpage>120</lpage><history><date date-type="received"><day>4</day><month>1</month><year>2014</year></date><date date-type="accepted"><day>16</day><month>1</month><year>2014</year></date></history><permissions><copyright-statement>© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For permissions, please email: journals.permissions@oup.com.</copyright-statement><copyright-year>2014</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<uri xlink:type="simple" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</uri>), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com</license-p></license></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="sfu001.pdf"></self-uri><abstract><p>Mammalian target of rapamycin inhibitor (mTOR-I)/proliferation signal inhibitors (PSI) including sirolimus and everolimus represent a new class of drugs increasingly used in solid-organ transplantation as alternatives to calcineurin inhibitors for patients with renal dysfunction, transplant coronary arterial vasculopathy or malignancy. The most frequently occurring mTOR-I/PSI-related adverse events are similar to those associated with other immunosuppressive therapies, but some side effects are more characteristic of proliferation signal inhibitors (e.g. lymphocele, arthralgia, oedema and hyperlipidaemia). The present paper review incidence, clinical presentation and mechanism of oedema within the clinical experience of mTOR-I/PSI in solid organ transplantation.</p></abstract><kwd-group><kwd>angio-oedema</kwd><kwd>oedema</kwd><kwd>everolimus</kwd><kwd>lymphoedema</kwd><kwd>proliferation signal inhibitor</kwd><kwd>sirolimus</kwd><kwd>VEGF-C</kwd></kwd-group><counts><page-count count="6"></page-count></counts></article-meta></front><body><p>Mammalian target of rapamycin inhibitor (mTOR-I)/proliferation signal inhibitors (PSI) including sirolimus (SRL) and everolimus (EVL) represent a new class of drugs increasingly used in solid organ transplantation as alternatives to calcineurin inhibitors for patients with renal dysfunction, transplant coronary arterial vasculopathy (TCAV) or malignancy [<xref rid="SFU001C1" ref-type="bibr">1</xref>]. Though generally well tolerated, the use of mTOR-I/PSI is associated with many side effects, which may account for the 20–40% drop-out rate for SRL/EVL in clinical Phase III trials. Some side effects are easily manageable, whereas others lead to drug discontinuation [<xref rid="SFU001C2" ref-type="bibr">2</xref>]. Oedema induced by mTOR-1/PSI takes different clinical forms ranging from the banal lymphocele to the dramatic angio-oedema (AE). This article reviews the incidence (Table <xref ref-type="table" rid="SFU001TB1">1</xref>) [<xref rid="SFU001C3" ref-type="bibr">3</xref>–<xref rid="SFU001C13" ref-type="bibr">13</xref>], clinical presentation (Table <xref ref-type="table" rid="SFU001TB2">2</xref>) [<xref rid="SFU001C14" ref-type="bibr">14</xref>–<xref rid="SFU001C24" ref-type="bibr">24</xref>] and mechanisms of oedema within the clinical experience of mTOR-I/PSI in solid organ transplantation.
<table-wrap id="SFU001TB1" position="float"><label>Table 1.</label><caption><p>Incidence of oedema induced by EVL in solid organ transplantation</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="char" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><thead><tr><th align="left" rowspan="2" colspan="1">Author</th><th align="left" rowspan="2" colspan="1">Study</th><th align="left" rowspan="2" colspan="1">Organ transplant</th><th align="left" rowspan="2" colspan="1">Follow-up (months)</th><th align="left" rowspan="2" colspan="1">EVL mean level and/or mean dosage</th><th align="left" colspan="2" rowspan="1">Oedema incidence<hr></hr></th></tr><tr><th align="left" rowspan="1" colspan="1">EVL</th><th align="left" rowspan="1" colspan="1">Control</th></tr></thead><tbody><tr><td rowspan="1" colspan="1">Lehmkuhl <italic>et al</italic>. [<xref rid="SFU001C3" ref-type="bibr">3</xref>]</td><td rowspan="1" colspan="1">Multicentre open-label study RAD2411</td><td rowspan="1" colspan="1">Heart transplant</td><td rowspan="1" colspan="1">12</td><td rowspan="1" colspan="1">4.1 ± 1.8 ng/mL</td><td rowspan="1" colspan="1"><list list-type="simple"><list-item><p>EVL, 91 patients</p></list-item><list-item><p>Peripheral oedema, 39.6%</p></list-item><list-item><p>Pericardial effusion, 35.3%</p></list-item><list-item><p>Pleural effusion, 24.2%</p></list-item></list></td><td rowspan="1" colspan="1"><list list-type="simple"><list-item><p>MMF, 83 patients</p></list-item><list-item><p>Peripheral oedema, 34.9%</p></list-item><list-item><p>Pericardial effusion, 25.3%</p></list-item><list-item><p>Pleural effusion, 13.3%</p></list-item></list></td></tr><tr><td rowspan="1" colspan="1">Gullestad <italic>et al.</italic> [<xref rid="SFU001C4" ref-type="bibr">4</xref>]</td><td rowspan="1" colspan="1">Multicentre randomized trial</td><td rowspan="1" colspan="1">Heart (<italic>n</italic>=190) and lung (<italic>n</italic>=92) transplant</td><td rowspan="1" colspan="1">12</td><td rowspan="1" colspan="1">3–8 ng/mL</td><td rowspan="1" colspan="1">EVL+, 140 (29.3%)</td><td rowspan="1" colspan="1">EVL−, 142 (8.5%)</td></tr><tr><td rowspan="1" colspan="1">Gullestad <italic>et al.</italic> [<xref rid="SFU001C5" ref-type="bibr">5</xref>]</td><td rowspan="1" colspan="1">Multicentre randomized trial</td><td rowspan="1" colspan="1">Heart (<italic>n</italic>=190) and lung (<italic>n</italic>=92) transplant</td><td rowspan="1" colspan="1">24</td><td rowspan="1" colspan="1">4.5 ± 1.4 ng/mL</td><td rowspan="1" colspan="1">EVL+, 103 (8.3%)</td><td rowspan="1" colspan="1">EVL−, 119 (8.7%)</td></tr><tr><td rowspan="1" colspan="1">Roman <italic>et al.</italic> [<xref rid="SFU001C6" ref-type="bibr">6</xref>]</td><td rowspan="1" colspan="1">Retrospective, EVERODATA lung substudy</td><td rowspan="1" colspan="1">Lung transplant</td><td rowspan="1" colspan="1">12</td><td rowspan="1" colspan="1">6.4 ± 2.8 ng/mL</td><td rowspan="1" colspan="1">5/65 (7.7%</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">De Simone <italic>et al.</italic> [<xref rid="SFU001C7" ref-type="bibr">7</xref>]</td><td rowspan="1" colspan="1">Randomized controlled trail, H2304 study group</td><td rowspan="1" colspan="1">Liver transplant</td><td rowspan="1" colspan="1">12</td><td rowspan="1" colspan="1">6–10 ng/mL</td><td rowspan="1" colspan="1">EVL+ reduced TAK 43/245 (17.6%)</td><td rowspan="1" colspan="1"><list list-type="simple"><list-item><p>TAC elimination, 42/231 (18.3%)</p></list-item><list-item><p>TAC control, 26/243 (10.8%)</p></list-item></list></td></tr><tr><td rowspan="1" colspan="1">Alegre <italic>et al.</italic> [<xref rid="SFU001C8" ref-type="bibr">8</xref>]</td><td rowspan="1" colspan="1">Retrospective</td><td rowspan="1" colspan="1">Liver transplant</td><td rowspan="1" colspan="1">48</td><td rowspan="1" colspan="1">5.5 ± 2.2 ng/mL</td><td rowspan="1" colspan="1">EVL overall, 13/57 (28.8%)</td><td rowspan="1" colspan="1"><list list-type="simple"><list-item><p>EVL monotherapy,</p></list-item><list-item><p>5/24 (20.8%)</p></list-item><list-item><p>EVL combination</p></list-item><list-item><p>8/30 (24.2%)</p></list-item></list></td></tr><tr><td rowspan="1" colspan="1">Saliba <italic>et al.</italic> [<xref rid="SFU001C9" ref-type="bibr">9</xref>]</td><td rowspan="1" colspan="1">Randomized controlled trail, H2304 study group</td><td rowspan="1" colspan="1">Liver transplant</td><td rowspan="1" colspan="1">24</td><td rowspan="1" colspan="1">AE</td><td rowspan="1" colspan="1">EVL+ reduced TAC, 6/245 (2.4%)</td><td rowspan="1" colspan="1"><list list-type="simple"><list-item><p>TAC elimination, 4/231 (1.7%)</p></list-item><list-item><p>TAC control, 5/243 (2.1%)</p></list-item></list></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Ascites</td><td rowspan="1" colspan="1">EVL+ reduced TAC, 11/245 (4.5%)</td><td rowspan="1" colspan="1"><list list-type="simple"><list-item><p>TAC elimination, 14/231 (6.1%)</p></list-item><list-item><p>TAC control, 11/243 (4.5%)</p></list-item></list></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Peripheral oedema</td><td rowspan="1" colspan="1">EVL+ reduced TAC, 55/245 (22.4%)</td><td rowspan="1" colspan="1"><list list-type="simple"><list-item><p>TAC elimination, 45/231 (19.7%)</p></list-item><list-item><p>TAC control, 36/243 (14.9%)</p></list-item></list></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Pleural effusion</td><td rowspan="1" colspan="1">EVL+ reduced TAC, 15/245 (6.1%)</td><td rowspan="1" colspan="1"><list list-type="simple"><list-item><p>TAC elimination, 7/231 (3.1%)</p></list-item><list-item><p>TAC control, 13/243 (5.4%)</p></list-item></list></td></tr><tr><td rowspan="1" colspan="1">Lorber <italic>et al.</italic> [<xref rid="SFU001C10" ref-type="bibr">10</xref>]</td><td rowspan="1" colspan="1">Randomized, multicentre Phase III study</td><td rowspan="1" colspan="1">Kidney transplant</td><td rowspan="1" colspan="1">36</td><td rowspan="1" colspan="1">EVL 1.5 mg/d</td><td rowspan="1" colspan="1">101/193 (52.3%)</td><td rowspan="1" colspan="1">MMF, 82/196 (41.8%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">EVL 3 mg/d</td><td rowspan="1" colspan="1">92/191 (47.4%)</td><td rowspan="1" colspan="1">MMF, 82/196 (41.8%)</td></tr><tr><td rowspan="1" colspan="1">Cotovio <italic>et al.</italic> [<xref rid="SFU001C11" ref-type="bibr">11</xref>]</td><td rowspan="1" colspan="1">Retrospective register-based study</td><td rowspan="1" colspan="1">Kidney transplant</td><td rowspan="1" colspan="1">6</td><td rowspan="1" colspan="1">5.9 ± 2.6 ng/mL</td><td rowspan="1" colspan="1">8 (5.3%)</td><td rowspan="1" colspan="1">–</td></tr><tr><td rowspan="1" colspan="1">Shihab <italic>et al.</italic> [<xref rid="SFU001C12" ref-type="bibr">12</xref>]</td><td rowspan="1" colspan="1">Randomized controlled trial</td><td rowspan="1" colspan="1">Kidney transplant</td><td rowspan="1" colspan="1">12</td><td rowspan="1" colspan="1"><3 ng/mL</td><td rowspan="1" colspan="1">18/29 (62.1%)</td><td rowspan="1" colspan="1">–</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3–6 ng/mL</td><td rowspan="1" colspan="1">94/212 (44.3%)</td><td rowspan="1" colspan="1">–</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">6–8 ng/mL</td><td rowspan="1" colspan="1">55/105 (52.4%)</td><td rowspan="1" colspan="1">–</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">≥8 ng/mL</td><td rowspan="1" colspan="1">17/26 (65.4%)</td><td rowspan="1" colspan="1">–</td></tr><tr><td rowspan="1" colspan="1">Takahashi <italic>et al.</italic> [<xref rid="SFU001C13" ref-type="bibr">13</xref>]</td><td rowspan="1" colspan="1">Multicentre, open-label randomized study</td><td rowspan="1" colspan="1">Kidney transplant</td><td rowspan="1" colspan="1">12</td><td rowspan="1" colspan="1">1.5 mg/day</td><td rowspan="1" colspan="1">EVL, 20/61 (32.8%)</td><td rowspan="1" colspan="1">MMF, 8/61 (13.1%)</td></tr></tbody></table><table-wrap-foot><fn id="fn1"><p>MMF, mycophenolate mofetil; TAC, tacrolimus.</p></fn></table-wrap-foot></table-wrap><table-wrap id="SFU001TB2" position="float"><label>Table 2.</label><caption><p>Case reports of oedema induced by mTOR-I/PSIs: clinical features</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><thead><tr><th align="left" rowspan="2" colspan="1">Reference</th><th align="left" rowspan="2" colspan="1">Organ transplant</th><th align="left" colspan="2" rowspan="1">mTOR-I/PSI<hr></hr></th><th align="left" colspan="3" rowspan="1">Oedema<hr></hr></th><th align="left" rowspan="2" colspan="1">Follow-up</th></tr><tr><th align="left" rowspan="1" colspan="1">Dosage</th><th align="left" rowspan="1" colspan="1">Level</th><th align="left" rowspan="1" colspan="1">Onset</th><th align="left" rowspan="1" colspan="1">Clinical features</th><th align="left" rowspan="1" colspan="1">Action</th></tr></thead><tbody><tr><td rowspan="3" colspan="1">[<xref rid="SFU001C14" ref-type="bibr">14</xref>]</td><td rowspan="3" colspan="1">Heart</td><td rowspan="1" colspan="1">EVL, 0.75 mg/day</td><td rowspan="1" colspan="1">8 ng/mL</td><td rowspan="1" colspan="1">1 month</td><td rowspan="1" colspan="1">Hand and forearms</td><td rowspan="2" colspan="1">EVL dose reduction</td><td rowspan="1" colspan="1">Partial resolution</td></tr><tr><td rowspan="1" colspan="1">EVL, 0.5 mg/day</td><td rowspan="1" colspan="1">5 ng/mL</td><td rowspan="1" colspan="1">1 month</td><td rowspan="1" colspan="1">Hand and forearms</td><td rowspan="1" colspan="1">Partial resolution</td></tr><tr><td rowspan="1" colspan="1">Switch to SRL, 1 mg/day</td><td rowspan="1" colspan="1">10 ng/mL</td><td rowspan="1" colspan="1">Few days</td><td rowspan="1" colspan="1">Increase in the oedema</td><td rowspan="1" colspan="1">Stop</td><td rowspan="1" colspan="1">Complete resolution 2 months after</td></tr><tr><td rowspan="2" colspan="1">[<xref rid="SFU001C15" ref-type="bibr">15</xref>]</td><td rowspan="2" colspan="1">Heart</td><td rowspan="1" colspan="1">EVL,</td><td rowspan="1" colspan="1">NA</td><td rowspan="1" colspan="1">36 months</td><td rowspan="1" colspan="1">Bilateral chylothorax</td><td rowspan="1" colspan="1">Switch EVL to MMF</td><td rowspan="1" colspan="1">Complete resolution within 8 months</td></tr><tr><td rowspan="1" colspan="1">Reintroduction of EVL (TCAV progression)</td><td rowspan="1" colspan="1">NA</td><td rowspan="1" colspan="1">4 months</td><td rowspan="1" colspan="1">Pleural effusion</td><td rowspan="1" colspan="1">EVL discontinuation</td><td rowspan="1" colspan="1">Complete resolution</td></tr><tr><td rowspan="2" colspan="1">[<xref rid="SFU001C16" ref-type="bibr">16</xref>]</td><td rowspan="2" colspan="1">Kidney</td><td rowspan="2" colspan="1">EVL, 0.5–1 mg/day</td><td rowspan="2" colspan="1">>3 ng/mL</td><td rowspan="2" colspan="1">12 months</td><td rowspan="2" colspan="1">Feet oedema</td><td rowspan="1" colspan="1">No</td><td rowspan="1" colspan="1">Progression to upper extremities and left breast</td></tr><tr><td rowspan="1" colspan="1">EVL discontinuation</td><td rowspan="1" colspan="1">Complete resolution within 3 months</td></tr><tr><td rowspan="1" colspan="1">[<xref rid="SFU001C17" ref-type="bibr">17</xref>]</td><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">EVL, 1.5 mg/day (6 patients)</td><td rowspan="1" colspan="1">3–8 ng/mL</td><td rowspan="1" colspan="1">2–41 days</td><td rowspan="1" colspan="1">AE</td><td rowspan="1" colspan="1"><list list-type="simple"><list-item><p>Hospitalization</p></list-item><list-item><p>IV prednisone and clemastin</p></list-item><list-item><p>Acetyl-salicylic acid stopped</p></list-item></list></td><td rowspan="1" colspan="1">Five patients were free from recurrence despite EVL maintenance. One patient experienced two recurrent episodes before under EVL, stopped</td></tr><tr><td rowspan="3" colspan="1">[<xref rid="SFU001C18" ref-type="bibr">18</xref>]</td><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">SRL, dosage NA</td><td rowspan="1" colspan="1">NA</td><td rowspan="1" colspan="1">3 months</td><td rowspan="1" colspan="1">Mild oedema on both legs, LUE and left breast, recurrent lymphangitis</td><td rowspan="1" colspan="1">SRL discontinuation</td><td rowspan="1" colspan="1">Complete resolution within few months</td></tr><tr><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">SRL, dosage NA</td><td rowspan="1" colspan="1">NA</td><td rowspan="1" colspan="1">6 months</td><td rowspan="1" colspan="1">Mild oedema on both legs and redness of RUE and right breast,</td><td rowspan="1" colspan="1">SRL discontinuation</td><td rowspan="1" colspan="1">Partial resolution, 60–70% within few months</td></tr><tr><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">SRL, dosage NA</td><td rowspan="1" colspan="1">NA</td><td rowspan="1" colspan="1">4 months</td><td rowspan="1" colspan="1">Oedema both legs, nephrotic syndrome</td><td rowspan="1" colspan="1">SRL discontinuation</td><td rowspan="1" colspan="1">Partial resolution, 80–90% within few weeks</td></tr><tr><td rowspan="2" colspan="1">[<xref rid="SFU001C19" ref-type="bibr">19</xref>]</td><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">SRL, 9.5 mg/day</td><td rowspan="1" colspan="1">26.3 ng/mL</td><td rowspan="1" colspan="1">36 months</td><td rowspan="1" colspan="1">Severe oedema and redness of LUE and left breast,</td><td rowspan="1" colspan="1">Reduction of SRL dosage (trough levels of 5–10 ng/mL)</td><td rowspan="1" colspan="1">Partial resolution, 60–70%</td></tr><tr><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">SRL, 2 mg/day</td><td rowspan="1" colspan="1">5–10 ng/mL</td><td rowspan="1" colspan="1">6 months</td><td rowspan="1" colspan="1">Severe oedema of RUE and right breast, functioning access RUE</td><td rowspan="1" colspan="1">SRL withdrawal, conversion to CSA</td><td rowspan="1" colspan="1">Partial resolution, 70–80%</td></tr><tr><td rowspan="3" colspan="1">[<xref rid="SFU001C20" ref-type="bibr">20</xref>]</td><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">SRL, 3 mg/day</td><td rowspan="1" colspan="1">10–18 ng/mL</td><td rowspan="1" colspan="1">30 months</td><td rowspan="1" colspan="1">Lymphoedema of the left upper limb</td><td rowspan="1" colspan="1">SRL withdrawal</td><td rowspan="1" colspan="1">Significant improvement</td></tr><tr><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">SRL, 3 mg/day</td><td rowspan="1" colspan="1">10–15 ng/mL</td><td rowspan="1" colspan="1">30 months</td><td rowspan="1" colspan="1">Lymphoedema of the left lower limb</td><td rowspan="1" colspan="1">SRL withdrawal</td><td rowspan="1" colspan="1">Significant improvement within few months</td></tr><tr><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">SRL, 3 mg/day</td><td rowspan="1" colspan="1">10–18 ng/mL</td><td rowspan="1" colspan="1">24 months</td><td rowspan="1" colspan="1">Lymphoedema of the left lower limb</td><td rowspan="1" colspan="1">SRL withdrawal</td><td rowspan="1" colspan="1">Significant improvement within few months</td></tr><tr><td rowspan="1" colspan="1">[<xref rid="SFU001C21" ref-type="bibr">21</xref>]</td><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">SRL, 5 mg/day</td><td rowspan="1" colspan="1">12–20 ng/mL</td><td rowspan="1" colspan="1">3 months</td><td rowspan="1" colspan="1">Generalized lymphoedema</td><td rowspan="1" colspan="1">SRL withdrawal</td><td rowspan="1" colspan="1">Complete resolution 3 months after</td></tr><tr><td rowspan="3" colspan="1">[<xref rid="SFU001C22" ref-type="bibr">22</xref>]</td><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">SRL, 19 mg/day</td><td rowspan="1" colspan="1">10.3 ng/mL</td><td rowspan="1" colspan="1">1 month</td><td rowspan="1" colspan="1">AE</td><td rowspan="1" colspan="1">Steroids + diphenhydramine and SRL withdrawal</td><td rowspan="1" colspan="1">Complete resolution 2 days after</td></tr><tr><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">SRL reintroduction, 20 mg/day</td><td rowspan="1" colspan="1">3.1 ng/mL</td><td rowspan="1" colspan="1">1 day</td><td rowspan="1" colspan="1">AE</td><td rowspan="1" colspan="1">Steroids + diphenhydramine and SRL withdrawal</td><td rowspan="1" colspan="1">Complete resolution 2 days after</td></tr><tr><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">SRL, 8 mg/day</td><td rowspan="1" colspan="1">19.4 ng/mL</td><td rowspan="1" colspan="1">14 days</td><td rowspan="1" colspan="1">AE</td><td rowspan="1" colspan="1">Steroids + diphenhydramine and SRL withdrawal</td><td rowspan="1" colspan="1">Complete resolution 2 days after. However, the patient inadvertently received two more daily 4 mg doses of SRL, and AE recurred. SRL was then switched to cyclosporin A, and there has been no recurrence in the subsequent 11 months</td></tr><tr><td rowspan="1" colspan="1">[<xref rid="SFU001C23" ref-type="bibr">23</xref>]</td><td rowspan="1" colspan="1">Kidney</td><td rowspan="1" colspan="1">SRL, 1–20 mg/day (5 patients)</td><td rowspan="1" colspan="1">5–19 ng/mL</td><td rowspan="1" colspan="1">1–5 months</td><td rowspan="1" colspan="1">Eyelid oedema of variable severity</td><td rowspan="1" colspan="1">Dose reduction, temporary or definitive SRL discontinuation</td><td rowspan="1" colspan="1">Complete resolution</td></tr><tr><td rowspan="1" colspan="1">[<xref rid="SFU001C24" ref-type="bibr">24</xref>]</td><td rowspan="1" colspan="1">Heart</td><td rowspan="1" colspan="1">SRL, 2 mg/day</td><td rowspan="1" colspan="1">2.5 ng/mL</td><td rowspan="1" colspan="1">12 months</td><td rowspan="1" colspan="1">Facial and right arm oedema</td><td rowspan="1" colspan="1">SRL withdrawal</td><td rowspan="1" colspan="1">Complete resolution 6 weeks after</td></tr></tbody></table><table-wrap-foot><fn id="fn2"><p>EVL, everolimus; SRL, sirolimus; TCAV, transplant coronary arterial vasculopathy; NA, not available; LUE, left upper extremity; RUE, right upper extremity; RLE, right lower extremity; CSA, cyclosporine.</p></fn></table-wrap-foot></table-wrap></p><sec id="s2"><title>Lymphocele</title><p>Lymphocele is a well-known complication after kidney transplantation. It occurs among 0.6–22% of symptomatic patients being treated with cyclosporine (CsA)-based immunosuppression [<xref rid="SFU001C25" ref-type="bibr">25</xref>–<xref rid="SFU001C31" ref-type="bibr">31</xref>] and 49% of asymptomatic cases detected by ultrasonography during a 2- to 11-year follow-up [<xref rid="SFU001C32" ref-type="bibr">32</xref>]. mTOR-I/PSI are associated with an increased incidence of mild or moderate lymphocele. In clinical studies, the rates of lymphocele in renal transplant patients receiving a 6-month treatment with EVL 1.5–3.0 mg/day, or SRL 2.0–5.0 mg/day were 6.4–15.2 [<xref rid="SFU001C33" ref-type="bibr">33</xref>] and 12–13% [<xref rid="SFU001C34" ref-type="bibr">34</xref>], respectively. Post-marketing experience with SRL has demonstrated an increased incidence of lymphoceles. Factors predisposing to lymphocele formation include drainage from open lymphatics divided during surgery to dissect the host iliac vessels [<xref rid="SFU001C29" ref-type="bibr">29</xref>, <xref rid="SFU001C35" ref-type="bibr">35</xref>], injured lymph channels in the donor kidney hilum vessels [<xref rid="SFU001C31" ref-type="bibr">31</xref>, <xref rid="SFU001C36" ref-type="bibr">36</xref>], acute allograft rejection episode [<xref rid="SFU001C26" ref-type="bibr">26</xref>, <xref rid="SFU001C37" ref-type="bibr">37</xref>, <xref rid="SFU001C38" ref-type="bibr">38</xref>], acute tubular necrosis [<xref rid="SFU001C26" ref-type="bibr">26</xref>], transplant kidney biopsy [<xref rid="SFU001C30" ref-type="bibr">30</xref>], retransplantation [<xref rid="SFU001C39" ref-type="bibr">39</xref>] and adult polycystic kidney disease as the original renal disease [<xref rid="SFU001C40" ref-type="bibr">40</xref>]. Clinical experience shows that mild lymphocele can resolve itself, while moderate lymphocele usually responds to povidine-iodine [<xref rid="SFU001C41" ref-type="bibr">41</xref>]. Although some patients who receive mTOR-1/PSI may develop early massive lymphocele that requires surgery, mTOR-1/PSI dose reduction or complete withdrawal is not necessary. Surgery for lymphocele is not common [<xref rid="SFU001C42" ref-type="bibr">42</xref>].</p></sec><sec id="s3"><title>Eyelid oedema</title><p>Eyelid swelling is often the herald of significant systemic or periorbital disease. The aetiological list is extensive. Many medications—topical, oral and parenteral—are well recognized to create eyelid swelling through generalized fluid retention, AE, urticaria or topical blepharoconjunctivitis. mTOR-1/PSI-related eyelid oedema in kidney transplant recipients was described in a few case reports of SRL- [<xref rid="SFU001C18" ref-type="bibr">18</xref>, <xref rid="SFU001C23" ref-type="bibr">23</xref>] and EVL-based [<xref rid="SFU001C43" ref-type="bibr">43</xref>] treatments. Development of eyelid oedema was gradual, occurring over 1–5 months after starting mTOR-I/PSI. The oedema may be mild and easily managed with low-dose furosemide and reduction of SRL dose was not warranted. In some patients, discontinuation of mTOR-I/PSI was followed by delayed resolution of the swelling, with full recovery taking as long as months. The underlying mechanism is unknown.</p></sec><sec id="s4"><title>Oedema and lymphoedema</title><p>Leg swelling is an extremely frequent symptom with a broad variety of largely differing causes. The most important mechanisms behind the symptom include venous and lymphatic pathology, volume overload, increased capillary permeability and lowered oncotic pressure. Therefore, the most frequent diseases associated with leg swelling are deep vein thrombosis and chronic venous insufficiency, primary or secondary lymphoedema, cardiac failure, hypoproteinaemia, idiopathic cyclic oedema and drug-induced oedema. Lymphoedema may be primary (congenital lymphatic abnormality) or secondary, frequently related to cancer treatment. Other causes of secondary lymphoedema include obstruction by tumour, infection (filariasis), recurrent cellulitis and connective tissue disease. A less-common form of oedema is lymphoedema, which causes an abnormality in the lymphatic system. The most common cause is interruption of the axillary lymphatic system by surgery and/or radiation therapy in women with breast cancer.</p><p>Unilateral or bilateral peripheral oedema/lymphoedema is common following the initiation of mTOR-I/PSI use [<xref rid="SFU001C24" ref-type="bibr">24</xref>, <xref rid="SFU001C43" ref-type="bibr">43</xref>] and frequently sufficiently severe enough to require medication discontinuation. However, it may be less frequent with EVL with a retrospective series reporting 4- to 5-fold less oedema when compared with matched SRL-treated patients (14 versus 64%), respectively [<xref rid="SFU001C14" ref-type="bibr">14</xref>]. It has been mentioned that a preponderance in any specific gender is unlikely and it develops 7 months to 2 years after the start of SRL (mean SRL levels ranging from 10 to 20 ng/mL) [<xref rid="SFU001C20" ref-type="bibr">20</xref>] or a few days to 36 months after the start of EVL (mean EVL levels ranging from 3 to 26 ng/mL) in an arm- or leg-localized lymphoedema form of varying severity (Table <xref ref-type="table" rid="SFU001TB2">2</xref>). Usually, peripheral oedema/lymphoedema was controlled with low doses of furosemide accompanied by reduction of the immunosuppressant [<xref rid="SFU001C43" ref-type="bibr">43</xref>]. mTOR-I/PSI-related lymphoedema is not dependent on its cumulative dosage and exposure duration. [<xref rid="SFU001C20" ref-type="bibr">20</xref>] Early discontinuation of the drug may prevent permanent disfigurement [<xref rid="SFU001C44" ref-type="bibr">44</xref>]. Moreover, the occurrence of limb lymphoedema in renal transplant recipients under SRL treatment, especially if on the same side as the haemodialysis access, should alert the transplant physician to the need for rapid SRL reduction or withdrawal, before complete obstruction occurs, further complicating an already disabling condition. [<xref rid="SFU001C19" ref-type="bibr">19</xref>] Close monitoring of this side effect is warranted. Recognizing this association may prevent many unnecessary, costly and invasive investigations. The pathophysiology seems to be due to altered lymphatic drainage [<xref rid="SFU001C18" ref-type="bibr">18</xref>, <xref rid="SFU001C19" ref-type="bibr">19</xref>]. The lymphatic vasculature transports extravasated tissue fluid, macromolecules and cells back into the blood circulation. One pathway of regulation of cell growth and proliferation is mediated by the regulatory associated protein of mTOR (raptor)—G protein β-subunit-like protein (GβL)—and mTOR complex, which is a target of rapamycin. Important downstream effectors of the mTOR system are the translation regulators p70S6 kinase and eukaryotic initiation factor 4E-binding protein [<xref rid="SFU001C45" ref-type="bibr">45</xref>]. The mTOR pathway is regulated by the PI3K/AKT kinase system, which is upregulated in tumours. Activation of PI3K/AKT causes activation of mTOR and promotes cell growth and proliferation. Lymphatic endothelium expresses VEGF receptor-3 (VEGFR-3), which is activated after binding to VEGF-C, and VEGF-D plays an important role in lymphangiogenesis. The gene that encodes VEGFR-3 (FLT4) is defective in most families with congenital hereditary lymphoedema [<xref rid="SFU001C46" ref-type="bibr">46</xref>] and impaired lymphangiogenesis and lymphoedema is observed in soluble VEGFR-3 (VEGF-C/VEGFD signaling inhibitor) expressing transgenic mice [<xref rid="SFU001C47" ref-type="bibr">47</xref>]. Missense mutations of VEGFR-3 prevent normal lymphatic growth in humans [<xref rid="SFU001C46" ref-type="bibr">46</xref>]. Huber <italic>et al</italic>. [<xref rid="SFU001C48" ref-type="bibr">48</xref>] demonstrate that rapamycin interferes with the intracellular VEGF-C-activated pathway of lymphatic endothelial cells. In rapamycin-treated animals, the anti lymphangiogenic effect during tissue regeneration occurs with prolonged lymphoedema, emphasizing the clinical relevance of this effect of the mTOR inhibition in solid organ transplant recipients.</p></sec><sec id="s5"><title>Effusions</title><p>An increased incidence of pleural and pericardial effusions has been described in mTOR-I/PSI-treated renal and cardiac transplant patients. The frequency of pericardial effusions following cardiac transplant is 3-fold greater in SRL-treated patients often requiring interventions such as drainage with or without SRL dose reductions [<xref rid="SFU001C49" ref-type="bibr">49</xref>–<xref rid="SFU001C51" ref-type="bibr">51</xref>]. The prevalence of effusions, pleural and pericardial, is similar between mycophenolate mofetil-(MMF) and EVL-treated patients, suggesting that this side effect may be PSI specific with greater frequency seen in SRL- versus EVL-treated patients [<xref rid="SFU001C3" ref-type="bibr">3</xref>]. Cases of pericardial tamponade have been described following the initiation of SRL both in <italic>de novo</italic> cardiac and late conversion heart transplant patients as well as non-cardiac transplants patients [<xref rid="SFU001C50" ref-type="bibr">50</xref>, <xref rid="SFU001C51" ref-type="bibr">51</xref>].</p></sec><sec id="s6"><title>Angio-oedema</title><p>AE is a self-limiting swelling that occurs in the deeper cutaneous and mucous membrane layers. Most cases of AE result from a reaction to food or drugs, but some episodes have no identifiable trigger.</p><p>Drug-induced AE is well documented in patients taking angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor antagonists (AIIRA), fibrinolytic agents, oestrogens and nonsteroidal anti-inflammatory drugs [<xref rid="SFU001C52" ref-type="bibr">52</xref>]. In addition, the frequency of ACEI-induced AE is high in transplant recipients, estimated at ∼1–5 versus 0.1–0.5% in the general population [<xref rid="SFU001C53" ref-type="bibr">53</xref>, <xref rid="SFU001C54" ref-type="bibr">54</xref>]. Abbosh <italic>et al.</italic> [<xref rid="SFU001C54" ref-type="bibr">54</xref>] reported a 24- and 5-fold higher incidence of AE in cardiac and renal transplant recipients, respectively, who were maintained on cyclosporin A, azathioprine and prednisone when compared with the general population. Several reports focused on the putative role of mTOR-I/PSI (SRL and EVL) in the pathogenesis of AE in organ transplant recipients [<xref rid="SFU001C17" ref-type="bibr">17</xref>, <xref rid="SFU001C22" ref-type="bibr">22</xref>, <xref rid="SFU001C55" ref-type="bibr">55</xref>–<xref rid="SFU001C58" ref-type="bibr">58</xref>]. In previous reports, AE associated with SRL occurred in 2.2–15% of patients [<xref rid="SFU001C57" ref-type="bibr">57</xref>, <xref rid="SFU001C59" ref-type="bibr">59</xref>]. The associated risk factors were ACEI therapy or African-American patients taking metoprolol [<xref rid="SFU001C55" ref-type="bibr">55</xref>, <xref rid="SFU001C57" ref-type="bibr">57</xref>], which are known to be associated with a higher frequency of AE [<xref rid="SFU001C60" ref-type="bibr">60</xref>–<xref rid="SFU001C62" ref-type="bibr">62</xref>]. Fuchs <italic>et al.</italic> [<xref rid="SFU001C17" ref-type="bibr">17</xref>] reported that 6 out of their 114 patients (5.3%) experienced for the first time in their lives the occurrence of lingual AE after switching them over to EVL. The time period from starting mTOR-I/PSI to the occurrence of AE ranged from 1 to 41 days. In all six patients, the AE was associated with petechial bleeding and with lingual bullae on the lateral part of the tongue and required hospitalization. At the time when the AE occurred, the following concomitant medications were used: acetyl-salicylic acid (ASS), ACE inhibitors or angiotensin-1-receptor inhibitors. Because the symptoms ceased after discontinuation of ASS in five out of the six patients, it may well be that ASS has triggered the occurrence of EVL-associated side effects. However, the time course after initiation of the immunosuppressive drug, the recurrence in one patient, and the favourable outcome after stopping the drug provide an argument for the pathogenic link between EVL and tongue AE [<xref rid="SFU001C17" ref-type="bibr">17</xref>]. Lingual oedema seems to occur predominantly within the first weeks after initiation of mTOR-I/PSI therapy. Drug trough level at presentation is variable within or below the target level or in the toxic range [<xref rid="SFU001C17" ref-type="bibr">17</xref>]. A lack of C1-esterase inhibitor could be excluded in all patients. A history of food and/or drug allergies and a lack of C1-esterase inhibitor could be excluded in all patients. In all cases, the condition responded promptly to parenteral steroids, H1 and H2 blockers and discontinuation of SRL. In the majority of patients, the AE seems to disappear without further recurrence after adequate therapy of the symptoms. The responsibility of mTOR-I/PSI in the pathogenesis of AE is suggested either as the sole aetiological factor or more probably as a cofactor [<xref rid="SFU001C17" ref-type="bibr">17</xref>, <xref rid="SFU001C22" ref-type="bibr">22</xref>, <xref rid="SFU001C56" ref-type="bibr">56</xref>, <xref rid="SFU001C57" ref-type="bibr">57</xref>] Several hypotheses can be advanced to explain the potential triggering role of mTOR-I/PSI: cytochrome p450 3A4 metabolism pathway interaction [<xref rid="SFU001C63" ref-type="bibr">63</xref>–<xref rid="SFU001C65" ref-type="bibr">65</xref>], experimental interaction between mTOR-I/PSI and the bradykinin pathway [<xref rid="SFU001C66" ref-type="bibr">66</xref>] and autoimmune diseases induced by mTOR-I/PSI introduction [<xref rid="SFU001C67" ref-type="bibr">67</xref>]. The absence of urticaria with AE suggests that mTOR-I/PSI-associated AEs are not IgE mediated [<xref rid="SFU001C17" ref-type="bibr">17</xref>, <xref rid="SFU001C22" ref-type="bibr">22</xref>, <xref rid="SFU001C56" ref-type="bibr">56</xref>, <xref rid="SFU001C57" ref-type="bibr">57</xref>].</p><p>In conclusion, mTOR-I/PSI may facilitate the occurrence of oedema. This specific adverse event can be easily managed without discontinuation of the drug. It is important to be aware of this phenomenon to avoid burdensome and cost-intense investigations for patients showing this symptom during treatment with mTOR-I/PSI.</p></sec><sec id="s7"><title>Conflict of interest statement</title><p>None declared.</p></sec></body><back><ref-list><title>References</title><ref id="SFU001C1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Valantine</surname><given-names>H</given-names></name><name><surname>Zuckermann</surname><given-names>A</given-names></name></person-group><article-title>From clinical trials to clinical practice: an overview of Certican (everolimus) in heart transplantation</article-title><source>J Heart Lung Transplant</source><year>2005</year><volume>24</volume><issue>Suppl 4</issue><comment>S185–190</comment></element-citation></ref><ref id="SFU001C2"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rostaing</surname><given-names>L</given-names></name><name><surname>Kamar</surname><given-names>N</given-names></name></person-group><article-title>mTOR inhibitor/proliferation signal inhibitors: entering or leaving the field?</article-title><source>J Nephrol</source><year>2010</year><volume>23</volume><fpage>133</fpage><pub-id pub-id-type="pmid">20155724</pub-id></element-citation></ref><ref id="SFU001C3"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lehmkuhl</surname><given-names>H</given-names></name><name><surname>Ross</surname><given-names>H</given-names></name><name><surname>Arizon</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Comparability of pattern of occurrence of pericardial effusions between everolimus- and MMF-based regimen in de novo cardiac transplant recipients</article-title><source>J Heart Lung Transplant</source><year>2009</year><volume>28</volume><issue>2 Suppl 1</issue><fpage>S170</fpage></element-citation></ref><ref id="SFU001C4"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gullestad</surname><given-names>L</given-names></name><name><surname>Iversen</surname><given-names>M</given-names></name><name><surname>Mortensen</surname><given-names>SA</given-names></name><etal></etal></person-group><article-title>Everolimus with reduced calcineurin inhibitor in thoracic transplant recipients with renal dysfunction: a multicenter, randomized trial</article-title><source>Transplantation</source><year>2010</year><volume>89</volume><fpage>864</fpage><lpage>872</lpage><pub-id pub-id-type="pmid">20061999</pub-id></element-citation></ref><ref id="SFU001C5"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gullestad</surname><given-names>L</given-names></name><name><surname>Mortensen</surname><given-names>SA</given-names></name><name><surname>Eiskjær</surname><given-names>H</given-names></name><etal></etal></person-group><article-title>Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomized trial</article-title><source>Transplantation</source><year>2010</year><volume>90</volume><fpage>1581</fpage><lpage>1589</lpage><pub-id pub-id-type="pmid">21030905</pub-id></element-citation></ref><ref id="SFU001C6"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Roman</surname><given-names>A</given-names></name><name><surname>Ussetti</surname><given-names>P</given-names></name><name><surname>Zurbano</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>A retrospective 12-month study of conversion to everolimus in lung transplant recipients</article-title><source>Transplant Proc</source><year>2011</year><volume>43</volume><fpage>2693</fpage><lpage>2698</lpage><pub-id pub-id-type="pmid">21911148</pub-id></element-citation></ref><ref id="SFU001C7"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>De Simone</surname><given-names>P</given-names></name><name><surname>Metselaar</surname><given-names>HJ</given-names></name><name><surname>Fischer</surname><given-names>L</given-names></name><etal></etal></person-group><article-title>Conversion from a calcineurin inhibitor to everolimus therapy in maintenance liver transplant recipients: a prospective, randomized, multicenter trial</article-title><source>Liver Transpl</source><year>2009</year><volume>15</volume><fpage>1262</fpage><lpage>1269</lpage><pub-id pub-id-type="pmid">19790150</pub-id></element-citation></ref><ref id="SFU001C8"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alegre</surname><given-names>C</given-names></name><name><surname>Jiménez</surname><given-names>C</given-names></name><name><surname>Manrique</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Everolimus monotherapy or combined therapy in liver transplantation: indications and results</article-title><source>Transplant Proc</source><year>2013</year><volume>45</volume><fpage>1971</fpage><lpage>1974</lpage><pub-id pub-id-type="pmid">23769086</pub-id></element-citation></ref><ref id="SFU001C9"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Saliba</surname><given-names>F</given-names></name><name><surname>De Simone</surname><given-names>P</given-names></name><name><surname>Nevens</surname><given-names>F</given-names></name><etal></etal></person-group><collab>H2304 Study Group</collab><article-title>Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study</article-title><source>Am J Transplant</source><year>2013</year><volume>13</volume><fpage>1734</fpage><lpage>1745</lpage><pub-id pub-id-type="pmid">23714399</pub-id></element-citation></ref><ref id="SFU001C10"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lorber</surname><given-names>MI</given-names></name><name><surname>Mulgaonkar</surname><given-names>S</given-names></name><name><surname>Butt</surname><given-names>KM</given-names></name><etal></etal></person-group><collab>B251 Study Group</collab><article-title>Everolimus versus mycophenolate mofetil in the prevention of rejection in de novo renal transplant recipients: a 3-year randomized, multicenter, phase III study</article-title><source>Transplantation</source><year>2005</year><volume>80</volume><fpage>244</fpage><lpage>252</lpage><pub-id pub-id-type="pmid">16041270</pub-id></element-citation></ref><ref id="SFU001C11"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cotovio</surname><given-names>P</given-names></name><name><surname>Neves</surname><given-names>M</given-names></name><name><surname>Santos</surname><given-names>L</given-names></name><etal></etal></person-group><article-title>Conversion to everolimus in kidney transplant recipients: to believe or not believe?</article-title><source>Transplant Proc</source><year>2012</year><volume>44</volume><fpage>2966</fpage><lpage>2970</lpage><pub-id pub-id-type="pmid">23195007</pub-id></element-citation></ref><ref id="SFU001C12"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shihab</surname><given-names>FS</given-names></name><name><surname>Cibrik</surname><given-names>D</given-names></name><name><surname>Chan</surname><given-names>L</given-names></name><etal></etal></person-group><article-title>Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine</article-title><source>Clin Transplant</source><year>2013</year><volume>27</volume><fpage>217</fpage><lpage>226</lpage><pub-id pub-id-type="pmid">23230975</pub-id></element-citation></ref><ref id="SFU001C13"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Takahashi</surname><given-names>K</given-names></name><name><surname>Uchida</surname><given-names>K</given-names></name><name><surname>Yoshimura</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>Efficacy and safety of concentration-controlled everolimus with reduced-dose cyclosporine in Japanese de novo renal transplant patients: 12-month results</article-title><source>Transplant Res</source><year>2013</year><volume>2</volume><fpage>14</fpage><pub-id pub-id-type="pmid">23866828</pub-id></element-citation></ref><ref id="SFU001C14"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moro</surname><given-names>JA</given-names></name><name><surname>Almenar</surname><given-names>L</given-names></name><name><surname>Martínez-Dolz</surname><given-names>L</given-names></name><etal></etal></person-group><article-title>mTOR inhibitors and unilateral edema</article-title><source>Rev Esp Cardiol</source><year>2008</year><volume>61</volume><fpage>987</fpage><lpage>988</lpage><pub-id pub-id-type="pmid">18775244</pub-id></element-citation></ref><ref id="SFU001C15"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fukushima</surname><given-names>N</given-names></name><name><surname>Saito</surname><given-names>S</given-names></name><name><surname>Sakata</surname><given-names>Y</given-names></name><etal></etal></person-group><article-title>A case of everolimus-associated chylothorax in a cardiac transplant recipient</article-title><source>Transplant Proc</source><year>2013</year><volume>45</volume><fpage>3144</fpage><lpage>3146</lpage><pub-id pub-id-type="pmid">24157052</pub-id></element-citation></ref><ref id="SFU001C16"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ersoy</surname><given-names>A</given-names></name><name><surname>Koca</surname><given-names>N</given-names></name></person-group><article-title>Everolimus-induced lymphedema in a renal transplant recipient: a case report</article-title><source>Exp Clin Transplant</source><year>2012</year><volume>10</volume><fpage>296</fpage><lpage>298</lpage><pub-id pub-id-type="pmid">22631070</pub-id></element-citation></ref><ref id="SFU001C17"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fuchs</surname><given-names>U</given-names></name><name><surname>Zittermann</surname><given-names>A</given-names></name><name><surname>Berthold</surname><given-names>HK</given-names></name><etal></etal></person-group><article-title>Immunosuppressive therapy with everolimus can be associated with potentially life-threatening lingual angioedema</article-title><source>Transplantation</source><year>2005</year><volume>79</volume><fpage>981</fpage><lpage>983</lpage><pub-id pub-id-type="pmid">15849555</pub-id></element-citation></ref><ref id="SFU001C18"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aboujaoude</surname><given-names>W</given-names></name><name><surname>Milgrom</surname><given-names>ML</given-names></name><name><surname>Govani</surname><given-names>MV</given-names></name></person-group><article-title>Lymphedema associated with sirolimus in renal transplant recipients</article-title><source>Transplantation</source><year>2004</year><volume>77</volume><fpage>1094</fpage><lpage>1096</lpage><pub-id pub-id-type="pmid">15087777</pub-id></element-citation></ref><ref id="SFU001C19"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Romagnoli</surname><given-names>J</given-names></name><name><surname>Citterio</surname><given-names>F</given-names></name><name><surname>Nanni</surname><given-names>G</given-names></name><etal></etal></person-group><article-title>Severe limb lymphedema in sirolimus-treated patients</article-title><source>Transplantation Proc</source><year>2005</year><volume>37</volume><fpage>834</fpage><lpage>836</lpage></element-citation></ref><ref id="SFU001C20"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Al-Otaibi</surname><given-names>T</given-names></name><name><surname>Ahamed</surname><given-names>N</given-names></name><name><surname>Nampoory</surname><given-names>MR</given-names></name><etal></etal></person-group><article-title>Lymphedema: an unusual complication of sirolimus therapy</article-title><source>Transplant Proc</source><year>2007</year><volume>39</volume><fpage>1207</fpage><lpage>1210</lpage><pub-id pub-id-type="pmid">17524934</pub-id></element-citation></ref><ref id="SFU001C21"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>De Bartolomeis</surname><given-names>C</given-names></name><name><surname>Collini</surname><given-names>A</given-names></name><name><surname>Rumberger</surname><given-names>B</given-names></name><etal></etal></person-group><article-title>Generalized lymphedema in a sirolimus-treated renal transplant patient</article-title><source>Clin Transplant</source><year>2008</year><volume>22</volume><fpage>254</fpage><lpage>257</lpage><pub-id pub-id-type="pmid">18339149</pub-id></element-citation></ref><ref id="SFU001C22"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wadei</surname><given-names>H</given-names></name><name><surname>Gruber</surname><given-names>SA</given-names></name><name><surname>El-Amm</surname><given-names>JM</given-names></name><etal></etal></person-group><article-title>Sirolimus-induced angioedema</article-title><source>Am J Transplant</source><year>2004</year><volume>4</volume><fpage>1002</fpage><lpage>1005</lpage><pub-id pub-id-type="pmid">15147436</pub-id></element-citation></ref><ref id="SFU001C23"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mohaupt</surname><given-names>MG</given-names></name><name><surname>Vogt</surname><given-names>B</given-names></name><name><surname>Frey</surname><given-names>FJ</given-names></name></person-group><article-title>Sirolimus-associated eyelid edema in kidney transplant recipients</article-title><source>Transplantation</source><year>2001</year><volume>72</volume><fpage>162</fpage><lpage>164</lpage><pub-id pub-id-type="pmid">11468553</pub-id></element-citation></ref><ref id="SFU001C24"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Papali</surname><given-names>A</given-names></name><name><surname>Giannetti</surname><given-names>N</given-names></name><name><surname>Cantarovich</surname><given-names>M</given-names></name></person-group><article-title>Unilateral upper extremity edema associated with sirolimus in a heart transplant patient</article-title><source>Transplantation</source><year>2007</year><volume>83</volume><fpage>240</fpage><lpage>241</lpage><pub-id pub-id-type="pmid">17264826</pub-id></element-citation></ref><ref id="SFU001C25"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Amante</surname><given-names>AJ</given-names></name><name><surname>Kahan</surname><given-names>BD</given-names></name></person-group><article-title>Technical complications of renal transplantation</article-title><source>Surg Clin North Am</source><year>1994</year><volume>74</volume><fpage>1117</fpage><pub-id pub-id-type="pmid">7940064</pub-id></element-citation></ref><ref id="SFU001C26"><label>26</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Khauli</surname><given-names>RB</given-names></name><name><surname>Stoff</surname><given-names>JS</given-names></name><name><surname>Lovewell</surname><given-names>T</given-names></name><etal></etal></person-group><article-title>Post-transplant lymphoceles: a critical look into the risk factors, pathophysiology and management</article-title><source>J Urol</source><year>1993</year><volume>150</volume><fpage>22</fpage><pub-id pub-id-type="pmid">8510262</pub-id></element-citation></ref><ref id="SFU001C27"><label>27</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Malovrh</surname><given-names>M</given-names></name><name><surname>Kandus</surname><given-names>A</given-names></name><name><surname>Buturovic-Ponikvar</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Frequency and clinical influence of lymphoceles after kidney transplantation</article-title><source>Transplant Proc</source><year>1990</year><volume>22</volume><fpage>1423</fpage><pub-id pub-id-type="pmid">2202117</pub-id></element-citation></ref><ref id="SFU001C28"><label>28</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bry</surname><given-names>J</given-names></name><name><surname>Hull</surname><given-names>D</given-names></name><name><surname>Bartus</surname><given-names>SA</given-names></name><etal></etal></person-group><article-title>Treatment of recurrent lymphoceles following renal transplantation: remarsupialization with omentoplasty</article-title><source>Transplantation</source><year>1990</year><volume>49</volume><fpage>477</fpage><pub-id pub-id-type="pmid">2407008</pub-id></element-citation></ref><ref id="SFU001C29"><label>29</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schweizer</surname><given-names>RT</given-names></name><name><surname>Cho</surname><given-names>S</given-names></name><name><surname>Koutz</surname><given-names>SL</given-names></name><etal></etal></person-group><article-title>Lymphoceles following renal transplantation</article-title><source>Arch Surg</source><year>1972</year><volume>104</volume><fpage>42</fpage><pub-id pub-id-type="pmid">4550174</pub-id></element-citation></ref><ref id="SFU001C30"><label>30</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Braun</surname><given-names>WE</given-names></name><name><surname>Banowsky</surname><given-names>LH</given-names></name><name><surname>Straffon</surname><given-names>RA</given-names></name><etal></etal></person-group><article-title>Lymphocytes associated with renal transplantation: report of 15 cases and review of the literature</article-title><source>Am J Med</source><year>1974</year><volume>57</volume><fpage>714</fpage><pub-id pub-id-type="pmid">4613172</pub-id></element-citation></ref><ref id="SFU001C31"><label>31</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zincke</surname><given-names>H</given-names></name><name><surname>Woods</surname><given-names>JE</given-names></name><name><surname>Leary</surname><given-names>FJ</given-names></name><etal></etal></person-group><article-title>Experience with lymphoceles after renal transplantation</article-title><source>Surgery</source><year>1975</year><volume>77</volume><fpage>444</fpage><pub-id pub-id-type="pmid">1092015</pub-id></element-citation></ref><ref id="SFU001C32"><label>32</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pollak</surname><given-names>R</given-names></name><name><surname>Veremis</surname><given-names>SA</given-names></name><name><surname>Maddux</surname><given-names>MS</given-names></name><etal></etal></person-group><article-title>The natural history of and therapy for perirenal fluid collections following renal transplantation</article-title><source>J Urol</source><year>1988</year><volume>140</volume><fpage>716</fpage><pub-id pub-id-type="pmid">3047434</pub-id></element-citation></ref><ref id="SFU001C33"><label>33</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vitko</surname><given-names>S</given-names></name><name><surname>Tedesco</surname><given-names>H</given-names></name><name><surname>Eris</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Everolimus with optimized cyclosporine dosing in renal transplant recipients: 6-month safety and efficacy results of two randomized studies</article-title><source>Am J Transplant</source><year>2004</year><volume>4</volume><fpage>626</fpage><pub-id pub-id-type="pmid">15023156</pub-id></element-citation></ref><ref id="SFU001C34"><label>34</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kahan</surname><given-names>BD</given-names></name></person-group><article-title>Efficacy of sirolimus compared with azathioprine for reduction of acute allograft rejection: a randomized multicentre study. The Rapamune US Study Group</article-title><source>Lancet</source><year>2000</year><fpage>356</fpage><lpage>202</lpage><comment>194</comment></element-citation></ref><ref id="SFU001C35"><label>35</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sansalone</surname><given-names>CV</given-names></name><name><surname>Aseni</surname><given-names>P</given-names></name><name><surname>Minetti</surname><given-names>E</given-names></name><etal></etal></person-group><article-title>Is lymphocele in renal transplantation an avoidable complication?</article-title><source>Am J Surg</source><year>2000</year><volume>179</volume><fpage>182</fpage><pub-id pub-id-type="pmid">10827314</pub-id></element-citation></ref><ref id="SFU001C36"><label>36</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kay</surname><given-names>R</given-names></name><name><surname>Fuchs</surname><given-names>E</given-names></name><name><surname>Barry</surname><given-names>JM</given-names></name></person-group><article-title>Management of postoperative pelvic lymphoceles</article-title><source>Urology</source><year>1980</year><volume>15</volume><fpage>345</fpage><pub-id pub-id-type="pmid">6994321</pub-id></element-citation></ref><ref id="SFU001C37"><label>37</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rashid</surname><given-names>A</given-names></name><name><surname>Posen</surname><given-names>G</given-names></name><name><surname>Couture</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>Accumulation of lymph around the transplanted kidney (lymphocele) mimicking renal allograft rejection</article-title><source>J Urol</source><year>1974</year><volume>111</volume><fpage>145</fpage><pub-id pub-id-type="pmid">4589848</pub-id></element-citation></ref><ref id="SFU001C38"><label>38</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bischof</surname><given-names>G</given-names></name><name><surname>Rockenschaub</surname><given-names>S</given-names></name><name><surname>Berlakovich</surname><given-names>G</given-names></name><etal></etal></person-group><article-title>Management of lymphoceles after kidney transplantation</article-title><source>Transpl Int</source><year>1998</year><volume>11</volume><fpage>277</fpage><pub-id pub-id-type="pmid">9704391</pub-id></element-citation></ref><ref id="SFU001C39"><label>39</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stephanian</surname><given-names>E</given-names></name><name><surname>Matas</surname><given-names>AJ</given-names></name><name><surname>Gores</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Retransplantation as a risk factor for lymphocele formation</article-title><source>Transplantation</source><year>1992</year><volume>53</volume><fpage>676</fpage><pub-id pub-id-type="pmid">1549865</pub-id></element-citation></ref><ref id="SFU001C40"><label>40</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Martinez-Ocana</surname><given-names>JC</given-names></name><name><surname>Lauzurica</surname><given-names>R</given-names></name><name><surname>Castellote</surname><given-names>E</given-names></name><etal></etal></person-group><article-title>Adult polycystic kidney disease: a risk factor for lymphocele formation after renal transplantation?</article-title><source>Transplant Proc</source><year>1995</year><volume>27</volume><fpage>2246</fpage><pub-id pub-id-type="pmid">7652792</pub-id></element-citation></ref><ref id="SFU001C41"><label>41</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Teruel</surname><given-names>JL</given-names></name><name><surname>Escobar</surname><given-names>EM</given-names></name><name><surname>Quereda</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>A simple and safe method for management of lymphocele after renal transplantation</article-title><source>J Urol</source><year>1983</year><volume>130</volume><fpage>1058</fpage><pub-id pub-id-type="pmid">6358528</pub-id></element-citation></ref><ref id="SFU001C42"><label>42</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Langer</surname><given-names>RM</given-names></name><name><surname>Kahan</surname><given-names>BD</given-names></name></person-group><article-title>Incidence, therapy, and consequences of lymphocele after sirolimus-cyclosporine-prednisone immunosuppression in renal transplant recipients</article-title><source>Transplantation</source><year>2002</year><volume>27</volume><fpage>804</fpage><pub-id pub-id-type="pmid">12364859</pub-id></element-citation></ref><ref id="SFU001C43"><label>43</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pascual</surname><given-names>J</given-names></name><name><surname>Marcén</surname><given-names>R</given-names></name><name><surname>Ortuño</surname><given-names>J</given-names></name></person-group><article-title>Clinical experience with everolimus (Certican): optimizing dose and tolerability</article-title><source>Transplantation</source><year>2005</year><volume>79</volume><issue>Suppl</issue><fpage>S80</fpage><lpage>S84</lpage><pub-id pub-id-type="pmid">15880021</pub-id></element-citation></ref><ref id="SFU001C44"><label>44</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Greager</surname><given-names>MA</given-names></name><name><surname>Dzay</surname></name></person-group><person-group person-group-type="editor"><name><surname>Fauchi</surname><given-names>AS</given-names></name><name><surname>Braunwald</surname><given-names>E</given-names></name><name><surname>Isselbacher</surname><given-names>KJ</given-names></name><etal></etal></person-group><article-title>Vascular disease of the extremities</article-title><source>Harrison's Principles of Internal Medicine</source><year>1998</year><volume>VJ</volume><publisher-loc>New York</publisher-loc><publisher-name>McGraw-Hill</publisher-name><fpage>1405</fpage></element-citation></ref><ref id="SFU001C45"><label>45</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stoeltzing</surname><given-names>O</given-names></name><name><surname>Meric-Bernstam</surname><given-names>F</given-names></name><name><surname>Ellis</surname><given-names>LM</given-names></name></person-group><article-title>Intracellular signaling in tumor and endothelial cells: the expected and, yet again, the unexpected</article-title><source>Cancer Cell</source><year>2006</year><volume>10</volume><fpage>89</fpage><lpage>91</lpage><pub-id pub-id-type="pmid">16904605</pub-id></element-citation></ref><ref id="SFU001C46"><label>46</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Karkkainen</surname><given-names>MJ</given-names></name><name><surname>Ferrell</surname><given-names>RE</given-names></name><name><surname>Lawrence</surname><given-names>EC</given-names></name><etal></etal></person-group><article-title>Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema</article-title><source>Nat Genet</source><year>2000</year><volume>25</volume><fpage>153</fpage><lpage>159</lpage><pub-id pub-id-type="pmid">10835628</pub-id></element-citation></ref><ref id="SFU001C47"><label>47</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mäkinen</surname><given-names>T</given-names></name><name><surname>Jussila</surname><given-names>L</given-names></name><name><surname>Veikkola</surname><given-names>T</given-names></name><etal></etal></person-group><article-title>Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3</article-title><source>Nat Med</source><year>2001</year><volume>7</volume><fpage>199</fpage><lpage>205</lpage><pub-id pub-id-type="pmid">11175851</pub-id></element-citation></ref><ref id="SFU001C48"><label>48</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huber</surname><given-names>S</given-names></name><name><surname>Bruns</surname><given-names>CJ</given-names></name><name><surname>Schmid</surname><given-names>G</given-names></name><etal></etal></person-group><article-title>Inhibition of the mammalian target of rapamycin impedes lymphangiogenesis</article-title><source>Kidney Int</source><year>2007</year><volume>71</volume><fpage>771</fpage><lpage>777</lpage><pub-id pub-id-type="pmid">17299523</pub-id></element-citation></ref><ref id="SFU001C49"><label>49</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Keogh</surname><given-names>A</given-names></name><name><surname>Richardson</surname><given-names>M</given-names></name><name><surname>Ruygrok</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized clinical trial</article-title><source>Circulation</source><year>2004</year><volume>110</volume><fpage>2694</fpage><lpage>2700</lpage><pub-id pub-id-type="pmid">15262845</pub-id></element-citation></ref><ref id="SFU001C50"><label>50</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Steele</surname><given-names>GH</given-names></name><name><surname>Adamkovic</surname><given-names>AB</given-names></name><name><surname>Demopoulos</surname><given-names>LA</given-names></name><etal></etal></person-group><article-title>Pericardial effusion coincident with sirolimus therapy: a review of Wyeth's safety database</article-title><source>Transplantation</source><year>2008</year><volume>85</volume><fpage>645</fpage><lpage>647</lpage><pub-id pub-id-type="pmid">18347546</pub-id></element-citation></ref><ref id="SFU001C51"><label>51</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bouzas-Mosquera</surname><given-names>A</given-names></name><name><surname>Crespo-Leiro</surname><given-names>MG</given-names></name><name><surname>Paniagua</surname><given-names>MJ</given-names></name><etal></etal></person-group><article-title>Adverse effects of mammalian target of rapamycin inhibitors during the postoperative period after cardiac transplantation</article-title><source>Transplant Proc</source><year>2008</year><volume>40</volume><fpage>3027</fpage><lpage>3030</lpage><pub-id pub-id-type="pmid">19010181</pub-id></element-citation></ref><ref id="SFU001C52"><label>52</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Agostoni</surname><given-names>A</given-names></name><name><surname>Cicardi</surname><given-names>M</given-names></name></person-group><article-title>Drug-induced angioedema without urticaria</article-title><source>Drug Saf</source><year>2001</year><volume>24</volume><fpage>599</fpage><lpage>606</lpage><pub-id pub-id-type="pmid">11480492</pub-id></element-citation></ref><ref id="SFU001C53"><label>53</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Israili</surname><given-names>ZH</given-names></name><name><surname>Hall</surname><given-names>WD</given-names></name></person-group><article-title>Cough and angioneurotic edema associated with angiotensin converting enzyme inhibitor therapy. A review of the literature and pathophysiology</article-title><source>Ann Intern Med</source><year>1992</year><volume>117</volume><fpage>234</fpage><lpage>242</lpage><pub-id pub-id-type="pmid">1616218</pub-id></element-citation></ref><ref id="SFU001C54"><label>54</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Abbosh</surname><given-names>J</given-names></name><name><surname>Anderson</surname><given-names>JA</given-names></name><name><surname>Levine</surname><given-names>AB</given-names></name><etal></etal></person-group><article-title>Angiotensin converting enzyme inhibitor-induced angioedema more prevalent in transplant patients</article-title><source>Ann Allergy Asthma Immunol</source><year>1999</year><volume>82</volume><fpage>473</fpage><lpage>476</lpage><pub-id pub-id-type="pmid">10353579</pub-id></element-citation></ref><ref id="SFU001C55"><label>55</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lykavieris</surname><given-names>P</given-names></name><name><surname>Frauger</surname><given-names>E</given-names></name><name><surname>Habes</surname><given-names>D</given-names></name><etal></etal></person-group><article-title>Angioedema in pediatric liver transplant recipients under tacrolimus immunosuppression</article-title><source>Transplantation</source><year>2003</year><volume>75</volume><fpage>152</fpage><lpage>155</lpage><pub-id pub-id-type="pmid">12544888</pub-id></element-citation></ref><ref id="SFU001C56"><label>56</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Burdese</surname><given-names>M</given-names></name><name><surname>Rossetti</surname><given-names>M</given-names></name><name><surname>Guarena</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Sirolimus and ACE-inhibitors: a note of caution</article-title><source>Transplantation</source><year>2005</year><volume>79</volume><fpage>251</fpage><lpage>252</lpage><pub-id pub-id-type="pmid">15665781</pub-id></element-citation></ref><ref id="SFU001C57"><label>57</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stallone</surname><given-names>G</given-names></name><name><surname>Infante</surname><given-names>B</given-names></name><name><surname>Di Paolo</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Sirolimus and angiotensin-converting enzyme inhibitors together induce tongue oedema in renal transplant recipients</article-title><source>Nephrol Dial Transplant</source><year>2004</year><volume>19</volume><fpage>2906</fpage><lpage>2908</lpage><pub-id pub-id-type="pmid">15496567</pub-id></element-citation></ref><ref id="SFU001C58"><label>58</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Montalbano</surname><given-names>M</given-names></name><name><surname>Neff</surname><given-names>GW</given-names></name><name><surname>Yamashiki</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>A retrospective review of liver transplant patients treated with sirolimus from a single center: an analysis of sirolimus-related complications</article-title><source>Transplantation</source><year>2004</year><volume>78</volume><fpage>264</fpage><lpage>268</lpage><pub-id pub-id-type="pmid">15280688</pub-id></element-citation></ref><ref id="SFU001C59"><label>59</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mahé</surname><given-names>E</given-names></name><name><surname>Morelon</surname><given-names>E</given-names></name><name><surname>Lechaton</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Angioedema in renal transplant recipients on sirolimus</article-title><source>Dermatology</source><year>2007</year><volume>214</volume><fpage>205</fpage><lpage>209</lpage><pub-id pub-id-type="pmid">17377381</pub-id></element-citation></ref><ref id="SFU001C60"><label>60</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Krikorian</surname><given-names>RK</given-names></name><name><surname>Quick</surname><given-names>A</given-names></name><name><surname>Tal</surname><given-names>A</given-names></name></person-group><article-title>Angioedema following the intravenous administration of metoprolol</article-title><source>Chest</source><year>1994</year><volume>106</volume><fpage>1922</fpage><lpage>1923</lpage><pub-id pub-id-type="pmid">7988234</pub-id></element-citation></ref><ref id="SFU001C61"><label>61</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gainer</surname><given-names>JV</given-names></name><name><surname>Nadeau</surname><given-names>JH</given-names></name><name><surname>Ryder</surname><given-names>D</given-names></name><etal></etal></person-group><article-title>Increased sensitivity to bradykinin among African Americans</article-title><source>J Allergy Clin Immunol</source><year>1996</year><volume>98</volume><fpage>283</fpage><lpage>287</lpage><pub-id pub-id-type="pmid">8757204</pub-id></element-citation></ref><ref id="SFU001C62"><label>62</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Morimoto</surname><given-names>T</given-names></name><name><surname>Gandhi</surname><given-names>TK</given-names></name><name><surname>Fiskio</surname><given-names>JM</given-names></name><etal></etal></person-group><article-title>An evaluation of risk factors for adverse drug events associated with angiotensin-converting enzyme inhibitors</article-title><source>J Eval Clin Pract</source><year>2004</year><volume>10</volume><fpage>499</fpage><lpage>509</lpage><pub-id pub-id-type="pmid">15482412</pub-id></element-citation></ref><ref id="SFU001C63"><label>63</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Flockhart</surname><given-names>DA</given-names></name><name><surname>Tanus-Santos</surname><given-names>JE</given-names></name></person-group><article-title>Implications of cytochrome P450 interactions when prescribing medication for hypertension</article-title><source>Arch Intern Med</source><year>2002</year><volume>162</volume><fpage>405</fpage><lpage>412</lpage><pub-id pub-id-type="pmid">11863472</pub-id></element-citation></ref><ref id="SFU001C64"><label>64</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lemahieu</surname><given-names>WP</given-names></name><name><surname>Maes</surname><given-names>BD</given-names></name><name><surname>Verbeke</surname><given-names>K</given-names></name><etal></etal></person-group><article-title>CYP3A4 and P-glycoprotein activity in healthy controls and transplant patients on cyclosporin vs tacrolimus vs sirolimus</article-title><source>Am J Transplant</source><year>2004</year><volume>4</volume><fpage>1514</fpage><lpage>1522</lpage><pub-id pub-id-type="pmid">15307840</pub-id></element-citation></ref><ref id="SFU001C65"><label>65</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barshes</surname><given-names>NR</given-names></name><name><surname>Goodpastor</surname><given-names>SE</given-names></name><name><surname>Goss</surname><given-names>JA</given-names></name></person-group><article-title>Sirolimus-atorvastatin drug interaction in the pancreatic islet transplant recipient</article-title><source>Transplantation</source><year>2003</year><volume>76</volume><fpage>1649</fpage><lpage>1650</lpage><pub-id pub-id-type="pmid">14702546</pub-id></element-citation></ref><ref id="SFU001C66"><label>66</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jeanmart</surname><given-names>H</given-names></name><name><surname>Malo</surname><given-names>O</given-names></name><name><surname>Carrier</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Comparative study of cyclosporine and tacrolimus vs newer immunosuppressants mycophenolate mofetil and rapamycin on coronary endothelial function</article-title><source>J Heart Lung Transplant</source><year>2002</year><volume>21</volume><fpage>990</fpage><lpage>998</lpage><pub-id pub-id-type="pmid">12231370</pub-id></element-citation></ref><ref id="SFU001C67"><label>67</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mahé</surname><given-names>E</given-names></name><name><surname>Morelon</surname><given-names>E</given-names></name><name><surname>Lechaton</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Cutaneous adverse events in renal transplant recipients on sirolimus-based therapy</article-title><source>Transplantation</source><year>2005</year><volume>79</volume><fpage>476</fpage><lpage>482</lpage><pub-id pub-id-type="pmid">15729175</pub-id></element-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000507 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000507 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= LymphedemaV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:4377777
|texte= Oedema, solid organ transplantation and mammalian target of rapamycin inhibitor/proliferation signal inhibitors (mTOR-I/PSIs)
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:25852858" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a LymphedemaV1
| This area was generated with Dilib version V0.6.31. |  |