Tacrolimus Trough Levels, Rejection and Renal Impairment in Liver Transplantation: A Systematic Review and Meta‐Analysis
We hypothesized that current trough concentrations of tacrolimus after liver transplantation are set too high, considering that clinical consequences of rejection are not severe while side effects are increased. We systematically reviewed 64 studies (32 randomized controlled trials and 32 observatio...
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| Veröffentlicht in: | American journal of transplantation 2012-10, Vol.12 (10), p.2797-2814 |
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| creator | Rodríguez‐Perálvarez, M. Germani, G. Darius, T. Lerut, J. Tsochatzis, E. Burroughs, A. K. |
| description | We hypothesized that current trough concentrations of tacrolimus after liver transplantation are set too high, considering that clinical consequences of rejection are not severe while side effects are increased. We systematically reviewed 64 studies (32 randomized controlled trials and 32 observational studies) to determine how lower tacrolimus trough concentrations than currently recommended affect acute rejection rates and renal impairment. Among randomized trials the mean of tacrolimus trough concentration during the first month was positively correlated with renal impairment within 1 year (r = 0.73; p = 0.003), but not with acute rejection, either defined using protocol biopsies (r =−0.37; p = 0.32) or not (r = 0.11; p = 0.49). A meta‐analysis of randomized trials directly comparing tacrolimus trough concentrations (five trials for acute rejection [n = 957] and two trials for renal impairment [n = 712]) showed that “reduced tacrolimus” trough concentrations (10 ng/mL). Lower trough concentrations of tacrolimus (6–10 ng/mL during the first month) would be more appropriate after liver transplantation. Regulatory authorities and the pharmaceutical industry should allow changes of regulatory drug information.
Evaluation of trough concentrations of tacrolimus after liver transplantation indicate that lower concentrations than currently recommended are safe in terms of acute cellular rejection, while reducing rates of renal impairment. |
| doi_str_mv | 10.1111/j.1600-6143.2012.04140.x |
| format | Article |
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Evaluation of trough concentrations of tacrolimus after liver transplantation indicate that lower concentrations than currently recommended are safe in terms of acute cellular rejection, while reducing rates of renal impairment.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/j.1600-6143.2012.04140.x</identifier><identifier>PMID: 22703529</identifier><language>eng</language><publisher>Malden, USA: Blackwell Publishing Inc</publisher><subject>Acute cellular rejection ; Biological and medical sciences ; Biopsy ; Clinical trials ; Drug therapy ; Graft Rejection ; Humans ; Immunosuppressive Agents - blood ; Immunosuppressive Agents - pharmacokinetics ; Kidney - physiopathology ; Liver ; Liver Transplantation ; Liver, biliary tract, pancreas, portal circulation, spleen ; Medical sciences ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; Randomized Controlled Trials as Topic ; Renal failure ; renal impairment ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the digestive system ; Surgery of the urinary system ; tacrolimus ; Tacrolimus - blood ; Tacrolimus - pharmacokinetics ; toxicity ; Transplants & implants ; trough concentration</subject><ispartof>American journal of transplantation, 2012-10, Vol.12 (10), p.2797-2814</ispartof><rights>Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5980-903977c6ae28f569d890c2f68c2fa1bccc9e23b708cc52d17ae7403273d03ad53</citedby><cites>FETCH-LOGICAL-c5980-903977c6ae28f569d890c2f68c2fa1bccc9e23b708cc52d17ae7403273d03ad53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1600-6143.2012.04140.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1600-6143.2012.04140.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26545802$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22703529$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rodríguez‐Perálvarez, M.</creatorcontrib><creatorcontrib>Germani, G.</creatorcontrib><creatorcontrib>Darius, T.</creatorcontrib><creatorcontrib>Lerut, J.</creatorcontrib><creatorcontrib>Tsochatzis, E.</creatorcontrib><creatorcontrib>Burroughs, A. K.</creatorcontrib><title>Tacrolimus Trough Levels, Rejection and Renal Impairment in Liver Transplantation: A Systematic Review and Meta‐Analysis</title><title>American journal of transplantation</title><addtitle>Am J Transplant</addtitle><description>We hypothesized that current trough concentrations of tacrolimus after liver transplantation are set too high, considering that clinical consequences of rejection are not severe while side effects are increased. We systematically reviewed 64 studies (32 randomized controlled trials and 32 observational studies) to determine how lower tacrolimus trough concentrations than currently recommended affect acute rejection rates and renal impairment. Among randomized trials the mean of tacrolimus trough concentration during the first month was positively correlated with renal impairment within 1 year (r = 0.73; p = 0.003), but not with acute rejection, either defined using protocol biopsies (r =−0.37; p = 0.32) or not (r = 0.11; p = 0.49). A meta‐analysis of randomized trials directly comparing tacrolimus trough concentrations (five trials for acute rejection [n = 957] and two trials for renal impairment [n = 712]) showed that “reduced tacrolimus” trough concentrations (<10 ng/mL) within the first month after liver transplantation were associated with less renal impairment at 1 year (RR = 0.51 [0.38–0.69]), with no significant influence on acute rejection (RR = 0.92 [0.65–1.31]) compared to “conventional tacrolimus” trough levels (>10 ng/mL). Lower trough concentrations of tacrolimus (6–10 ng/mL during the first month) would be more appropriate after liver transplantation. Regulatory authorities and the pharmaceutical industry should allow changes of regulatory drug information.
Evaluation of trough concentrations of tacrolimus after liver transplantation indicate that lower concentrations than currently recommended are safe in terms of acute cellular rejection, while reducing rates of renal impairment.</description><subject>Acute cellular rejection</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Clinical trials</subject><subject>Drug therapy</subject><subject>Graft Rejection</subject><subject>Humans</subject><subject>Immunosuppressive Agents - blood</subject><subject>Immunosuppressive Agents - pharmacokinetics</subject><subject>Kidney - physiopathology</subject><subject>Liver</subject><subject>Liver Transplantation</subject><subject>Liver, biliary tract, pancreas, portal circulation, spleen</subject><subject>Medical sciences</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nephropathies. Renovascular diseases. Renal failure</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Renal failure</subject><subject>renal impairment</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the digestive system</subject><subject>Surgery of the urinary system</subject><subject>tacrolimus</subject><subject>Tacrolimus - blood</subject><subject>Tacrolimus - pharmacokinetics</subject><subject>toxicity</subject><subject>Transplants & implants</subject><subject>trough concentration</subject><issn>1600-6135</issn><issn>1600-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1DAQxy1ERT_gFZAlhMSBDWM7ThwkDqsK2qJFSLCcLa8zAUf52MbJttsTj9Bn5Emwu8siccIHe0b-_WdG8yeEMkhYOG_qhGUAs4ylIuHAeAIpSyG5fURODh-PD7GQx-TU-xqA5VzxJ-SY8xyE5MUJuVsaO_SNaydPl0M_ff9BF7jBxr-mX7BGO7q-o6YrQ9aZhl61a-OGFruRuo4u3AaHIDOdXzemG02k39I5_br1I7YhtUG3cXjzUOITjubXz_t5KLT1zj8lR5VpPD7bv2fk24f3y_PL2eLzxdX5fDGzslAwK0AUeW4zg1xVMitKVYDlVabCZdjKWlsgF6sclLWSlyw3mKcgeC5KEKaU4oy82tVdD_31hH7UrfMWmzAx9pPXjHMQmVIQ0Rf_oHU_DWHeQDEmIaKRUjsqbM77ASu9Hlxrhq1mEDmmax1Xr6MNOvqjH_zRt0H6fN9gWrVYHoR_DAnAyz1gvDVNFXZrnf_LZTKVCnjg3u24G9fg9r8H0POPyxiJ3ygFq68</recordid><startdate>201210</startdate><enddate>201210</enddate><creator>Rodríguez‐Perálvarez, M.</creator><creator>Germani, G.</creator><creator>Darius, T.</creator><creator>Lerut, J.</creator><creator>Tsochatzis, E.</creator><creator>Burroughs, A. K.</creator><general>Blackwell Publishing Inc</general><general>Wiley</general><general>Elsevier Limited</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201210</creationdate><title>Tacrolimus Trough Levels, Rejection and Renal Impairment in Liver Transplantation: A Systematic Review and Meta‐Analysis</title><author>Rodríguez‐Perálvarez, M. ; Germani, G. ; Darius, T. ; Lerut, J. ; Tsochatzis, E. ; Burroughs, A. K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5980-903977c6ae28f569d890c2f68c2fa1bccc9e23b708cc52d17ae7403273d03ad53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Acute cellular rejection</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Clinical trials</topic><topic>Drug therapy</topic><topic>Graft Rejection</topic><topic>Humans</topic><topic>Immunosuppressive Agents - blood</topic><topic>Immunosuppressive Agents - pharmacokinetics</topic><topic>Kidney - physiopathology</topic><topic>Liver</topic><topic>Liver Transplantation</topic><topic>Liver, biliary tract, pancreas, portal circulation, spleen</topic><topic>Medical sciences</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nephropathies. Renovascular diseases. Renal failure</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Renal failure</topic><topic>renal impairment</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the digestive system</topic><topic>Surgery of the urinary system</topic><topic>tacrolimus</topic><topic>Tacrolimus - blood</topic><topic>Tacrolimus - pharmacokinetics</topic><topic>toxicity</topic><topic>Transplants & implants</topic><topic>trough concentration</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rodríguez‐Perálvarez, M.</creatorcontrib><creatorcontrib>Germani, G.</creatorcontrib><creatorcontrib>Darius, T.</creatorcontrib><creatorcontrib>Lerut, J.</creatorcontrib><creatorcontrib>Tsochatzis, E.</creatorcontrib><creatorcontrib>Burroughs, A. K.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rodríguez‐Perálvarez, M.</au><au>Germani, G.</au><au>Darius, T.</au><au>Lerut, J.</au><au>Tsochatzis, E.</au><au>Burroughs, A. K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tacrolimus Trough Levels, Rejection and Renal Impairment in Liver Transplantation: A Systematic Review and Meta‐Analysis</atitle><jtitle>American journal of transplantation</jtitle><addtitle>Am J Transplant</addtitle><date>2012-10</date><risdate>2012</risdate><volume>12</volume><issue>10</issue><spage>2797</spage><epage>2814</epage><pages>2797-2814</pages><issn>1600-6135</issn><eissn>1600-6143</eissn><abstract>We hypothesized that current trough concentrations of tacrolimus after liver transplantation are set too high, considering that clinical consequences of rejection are not severe while side effects are increased. We systematically reviewed 64 studies (32 randomized controlled trials and 32 observational studies) to determine how lower tacrolimus trough concentrations than currently recommended affect acute rejection rates and renal impairment. Among randomized trials the mean of tacrolimus trough concentration during the first month was positively correlated with renal impairment within 1 year (r = 0.73; p = 0.003), but not with acute rejection, either defined using protocol biopsies (r =−0.37; p = 0.32) or not (r = 0.11; p = 0.49). A meta‐analysis of randomized trials directly comparing tacrolimus trough concentrations (five trials for acute rejection [n = 957] and two trials for renal impairment [n = 712]) showed that “reduced tacrolimus” trough concentrations (<10 ng/mL) within the first month after liver transplantation were associated with less renal impairment at 1 year (RR = 0.51 [0.38–0.69]), with no significant influence on acute rejection (RR = 0.92 [0.65–1.31]) compared to “conventional tacrolimus” trough levels (>10 ng/mL). Lower trough concentrations of tacrolimus (6–10 ng/mL during the first month) would be more appropriate after liver transplantation. Regulatory authorities and the pharmaceutical industry should allow changes of regulatory drug information.
Evaluation of trough concentrations of tacrolimus after liver transplantation indicate that lower concentrations than currently recommended are safe in terms of acute cellular rejection, while reducing rates of renal impairment.</abstract><cop>Malden, USA</cop><pub>Blackwell Publishing Inc</pub><pmid>22703529</pmid><doi>10.1111/j.1600-6143.2012.04140.x</doi><tpages>18</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acute cellular rejection Biological and medical sciences Biopsy Clinical trials Drug therapy Graft Rejection Humans Immunosuppressive Agents - blood Immunosuppressive Agents - pharmacokinetics Kidney - physiopathology Liver Liver Transplantation Liver, biliary tract, pancreas, portal circulation, spleen Medical sciences Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure Randomized Controlled Trials as Topic Renal failure renal impairment Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the digestive system Surgery of the urinary system tacrolimus Tacrolimus - blood Tacrolimus - pharmacokinetics toxicity Transplants & implants trough concentration |
| title | Tacrolimus Trough Levels, Rejection and Renal Impairment in Liver Transplantation: A Systematic Review and Meta‐Analysis |
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