In Vitro and In Vivo Renoprotective Effects of Telbivudine in Chronic Hepatitis B Patients Receiving Nucleotide Analogue
Aim Renal toxicity of adefovir disoproxil (ADV) and tenofovir disoproxil fumarate (TDF) is a significant concern in chronic hepatitis B (CHB) patients. Early observational clinical data suggested that telbivudine (LdT) might have renoprotective effects. Methods In this prospective study, consecutive...
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| Veröffentlicht in: | Digestive diseases and sciences 2019-12, Vol.64 (12), p.3630-3641 |
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| creator | Mak, Lung-Yi Liu, Sze-Hang Yap, Desmond Yat-Hin Seto, Wai-Kay Wong, Danny Ka-Ho Fung, James Chan, Tak-Mao Lai, Ching-Lung Yuen, Man-Fung |
| description | Aim
Renal toxicity of adefovir disoproxil (ADV) and tenofovir disoproxil fumarate (TDF) is a significant concern in chronic hepatitis B (CHB) patients. Early observational clinical data suggested that telbivudine (LdT) might have renoprotective effects.
Methods
In this prospective study, consecutive CHB patients on combined lamivudine (LAM) + ADV/TDF were switched to LdT + ADV/TDF at recruitment and were followed up for 24 months. Estimated glomerular filtration rate (eGFR) was calculated with the modification of diet in renal disease equation. The effects of LdT on cell viability and expression of kidney injury or apoptotic biomarkers were investigated in cultured renal tubular epithelial cell line HK-2.
Results
Thirty-one patients (median age 55 years, 90.3% male) were recruited (54.8% TDF: 45.2% ADV). Serum HBV DNA was undetectable at all time points. Median eGFR was 70.2 (IQR 62.6–77.9) and 81.5 (IQR 63.6–99.1) mL/min/1.73 m
2
at baseline and 24 months, respectively (
p
|
| doi_str_mv | 10.1007/s10620-019-05717-0 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_journals_2252713693</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A712935520</galeid><sourcerecordid>A712935520</sourcerecordid><originalsourceid>FETCH-LOGICAL-c442t-135690126e37fc404df2d3836aab5fd2aeb68bb0d6f72f0fa6097a006e1a0d273</originalsourceid><addsrcrecordid>eNp9kVFrFDEUhYNY7Lb6B3yQgM9Tb5KdZOdxXaotFFtK9TVkkps1ZTZZk5ml_nvTbmsRpOQh9ybfudzDIeQ9gxMGoD4VBpJDA6xroFVMNfCKzFirRMNbuXhNZsBkrRmTh-SolFsA6BSTb8ihYHwBooMZuTuP9EcYc6ImOvrQ7BK9xpi2OY1ox7BDeup9rQpNnt7g0Ifd5EJEGiJd_cwpBkvPcGvGMIZCP9OrWmGs-DVaDLsQ1_TbZAdMY3BIl9EMaT3hW3LgzVDw3eN9TL5_Ob1ZnTUXl1_PV8uLxs7nfGyYaGUHjEsUyts5zJ3nTiyENKZvveMGe7noe3DSK-7BG1k9GgCJzIDjShyTj_u51c-vCcuob9OU6xJFc95yxYTsxDO1NgPqEH0as7GbUKxeKsY70bYcKnXyH6oeh5tgU0Qf6vs_Ar4X2JxKyej1NoeNyb81A32fod5nqGuG-iFDfS_68Ljx1G_Q_ZU8hVYBsQdK_YprzM-WXhj7B_bBpaE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2252713693</pqid></control><display><type>article</type><title>In Vitro and In Vivo Renoprotective Effects of Telbivudine in Chronic Hepatitis B Patients Receiving Nucleotide Analogue</title><source>MEDLINE</source><source>SpringerNature Complete Journals</source><creator>Mak, Lung-Yi ; Liu, Sze-Hang ; Yap, Desmond Yat-Hin ; Seto, Wai-Kay ; Wong, Danny Ka-Ho ; Fung, James ; Chan, Tak-Mao ; Lai, Ching-Lung ; Yuen, Man-Fung</creator><creatorcontrib>Mak, Lung-Yi ; Liu, Sze-Hang ; Yap, Desmond Yat-Hin ; Seto, Wai-Kay ; Wong, Danny Ka-Ho ; Fung, James ; Chan, Tak-Mao ; Lai, Ching-Lung ; Yuen, Man-Fung</creatorcontrib><description>Aim
Renal toxicity of adefovir disoproxil (ADV) and tenofovir disoproxil fumarate (TDF) is a significant concern in chronic hepatitis B (CHB) patients. Early observational clinical data suggested that telbivudine (LdT) might have renoprotective effects.
Methods
In this prospective study, consecutive CHB patients on combined lamivudine (LAM) + ADV/TDF were switched to LdT + ADV/TDF at recruitment and were followed up for 24 months. Estimated glomerular filtration rate (eGFR) was calculated with the modification of diet in renal disease equation. The effects of LdT on cell viability and expression of kidney injury or apoptotic biomarkers were investigated in cultured renal tubular epithelial cell line HK-2.
Results
Thirty-one patients (median age 55 years, 90.3% male) were recruited (54.8% TDF: 45.2% ADV). Serum HBV DNA was undetectable at all time points. Median eGFR was 70.2 (IQR 62.6–77.9) and 81.5 (IQR 63.6–99.1) mL/min/1.73 m
2
at baseline and 24 months, respectively (
p
< 0.001). Downstaging of chronic kidney disease was observed in eight (25.8%) patients and was more common in ADV-treated compared to TDF-treated patients (7/8 vs. 1/17,
p
= 0.011; OR 16, 95% CI 1.643–155.766,
p
= 0.017). In vitro data showed that adding LdT to ADV or TDF was associated with improved cell viability and lower expression of injury and apoptotic biomarkers compared with ADV or TDF alone. Treatment was prematurely discontinued in four(12.9%) patients due to myalgia.
Conclusions
Clinical and in vitro data suggest that LdT has renoprotective effects in patients on long-term ADV/TDF treatment. LdT may be considered as an adjuvant therapy in this special group of patients with renal impairment (NCT03778567).</description><identifier>ISSN: 0163-2116</identifier><identifier>EISSN: 1573-2568</identifier><identifier>DOI: 10.1007/s10620-019-05717-0</identifier><identifier>PMID: 31280390</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Activating Transcription Factor 4 - drug effects ; Activating Transcription Factor 4 - genetics ; Adefovir dipivoxil ; Adenine - adverse effects ; Adenine - analogs & derivatives ; Adenine - pharmacology ; Analysis ; Antiretroviral drugs ; Antiviral Agents - pharmacology ; Antiviral Agents - therapeutic use ; Antiviral drugs ; Apoptosis ; Apoptosis - drug effects ; Biochemistry ; Biomarkers ; Caspase 12 - drug effects ; Caspase 12 - genetics ; Cell Line ; Cell Survival - drug effects ; Chronic kidney failure ; Cytotoxicity ; Deoxyribonucleic acid ; DNA ; Endoplasmic Reticulum Chaperone BiP ; Enzymes ; Epithelial Cells ; Female ; Gastroenterology ; Glomerular Filtration Rate ; Heat-Shock Proteins - drug effects ; Heat-Shock Proteins - genetics ; Hepatitis ; Hepatitis A Virus Cellular Receptor 1 - drug effects ; Hepatitis A Virus Cellular Receptor 1 - genetics ; Hepatitis B ; Hepatitis B, Chronic - complications ; Hepatitis B, Chronic - drug therapy ; Hepatology ; Humans ; In Vitro Techniques ; Interferon ; Interleukin-18 - genetics ; Kidney diseases ; Kidney Tubules ; Lamivudine ; Lamivudine - pharmacology ; Lipocalin-2 - drug effects ; Lipocalin-2 - genetics ; Liver ; Male ; Medical research ; Medicine ; Medicine & Public Health ; Medicine, Experimental ; Middle Aged ; Mitochondrial DNA ; Mortality ; Oncology ; Organophosphonates - adverse effects ; Organophosphonates - pharmacology ; Original Article ; Prospective Studies ; Protective Agents ; Renal Insufficiency, Chronic - chemically induced ; Renal Insufficiency, Chronic - complications ; Renal Insufficiency, Chronic - metabolism ; Severity of Illness Index ; Studies ; Telbivudine ; Telbivudine - therapeutic use ; Tenofovir ; Tenofovir - adverse effects ; Tenofovir - pharmacology ; Transplant Surgery</subject><ispartof>Digestive diseases and sciences, 2019-12, Vol.64 (12), p.3630-3641</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>COPYRIGHT 2019 Springer</rights><rights>Digestive Diseases and Sciences is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-135690126e37fc404df2d3836aab5fd2aeb68bb0d6f72f0fa6097a006e1a0d273</citedby><cites>FETCH-LOGICAL-c442t-135690126e37fc404df2d3836aab5fd2aeb68bb0d6f72f0fa6097a006e1a0d273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10620-019-05717-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10620-019-05717-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31280390$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mak, Lung-Yi</creatorcontrib><creatorcontrib>Liu, Sze-Hang</creatorcontrib><creatorcontrib>Yap, Desmond Yat-Hin</creatorcontrib><creatorcontrib>Seto, Wai-Kay</creatorcontrib><creatorcontrib>Wong, Danny Ka-Ho</creatorcontrib><creatorcontrib>Fung, James</creatorcontrib><creatorcontrib>Chan, Tak-Mao</creatorcontrib><creatorcontrib>Lai, Ching-Lung</creatorcontrib><creatorcontrib>Yuen, Man-Fung</creatorcontrib><title>In Vitro and In Vivo Renoprotective Effects of Telbivudine in Chronic Hepatitis B Patients Receiving Nucleotide Analogue</title><title>Digestive diseases and sciences</title><addtitle>Dig Dis Sci</addtitle><addtitle>Dig Dis Sci</addtitle><description>Aim
Renal toxicity of adefovir disoproxil (ADV) and tenofovir disoproxil fumarate (TDF) is a significant concern in chronic hepatitis B (CHB) patients. Early observational clinical data suggested that telbivudine (LdT) might have renoprotective effects.
Methods
In this prospective study, consecutive CHB patients on combined lamivudine (LAM) + ADV/TDF were switched to LdT + ADV/TDF at recruitment and were followed up for 24 months. Estimated glomerular filtration rate (eGFR) was calculated with the modification of diet in renal disease equation. The effects of LdT on cell viability and expression of kidney injury or apoptotic biomarkers were investigated in cultured renal tubular epithelial cell line HK-2.
Results
Thirty-one patients (median age 55 years, 90.3% male) were recruited (54.8% TDF: 45.2% ADV). Serum HBV DNA was undetectable at all time points. Median eGFR was 70.2 (IQR 62.6–77.9) and 81.5 (IQR 63.6–99.1) mL/min/1.73 m
2
at baseline and 24 months, respectively (
p
< 0.001). Downstaging of chronic kidney disease was observed in eight (25.8%) patients and was more common in ADV-treated compared to TDF-treated patients (7/8 vs. 1/17,
p
= 0.011; OR 16, 95% CI 1.643–155.766,
p
= 0.017). In vitro data showed that adding LdT to ADV or TDF was associated with improved cell viability and lower expression of injury and apoptotic biomarkers compared with ADV or TDF alone. Treatment was prematurely discontinued in four(12.9%) patients due to myalgia.
Conclusions
Clinical and in vitro data suggest that LdT has renoprotective effects in patients on long-term ADV/TDF treatment. LdT may be considered as an adjuvant therapy in this special group of patients with renal impairment (NCT03778567).</description><subject>Activating Transcription Factor 4 - drug effects</subject><subject>Activating Transcription Factor 4 - genetics</subject><subject>Adefovir dipivoxil</subject><subject>Adenine - adverse effects</subject><subject>Adenine - analogs & derivatives</subject><subject>Adenine - pharmacology</subject><subject>Analysis</subject><subject>Antiretroviral drugs</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Antiviral drugs</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biochemistry</subject><subject>Biomarkers</subject><subject>Caspase 12 - drug effects</subject><subject>Caspase 12 - genetics</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>Chronic kidney failure</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Endoplasmic Reticulum Chaperone BiP</subject><subject>Enzymes</subject><subject>Epithelial Cells</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Glomerular Filtration Rate</subject><subject>Heat-Shock Proteins - drug effects</subject><subject>Heat-Shock Proteins - genetics</subject><subject>Hepatitis</subject><subject>Hepatitis A Virus Cellular Receptor 1 - drug effects</subject><subject>Hepatitis A Virus Cellular Receptor 1 - genetics</subject><subject>Hepatitis B</subject><subject>Hepatitis B, Chronic - complications</subject><subject>Hepatitis B, Chronic - drug therapy</subject><subject>Hepatology</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Interferon</subject><subject>Interleukin-18 - genetics</subject><subject>Kidney diseases</subject><subject>Kidney Tubules</subject><subject>Lamivudine</subject><subject>Lamivudine - pharmacology</subject><subject>Lipocalin-2 - drug effects</subject><subject>Lipocalin-2 - genetics</subject><subject>Liver</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Medicine, Experimental</subject><subject>Middle Aged</subject><subject>Mitochondrial DNA</subject><subject>Mortality</subject><subject>Oncology</subject><subject>Organophosphonates - adverse effects</subject><subject>Organophosphonates - pharmacology</subject><subject>Original Article</subject><subject>Prospective Studies</subject><subject>Protective Agents</subject><subject>Renal Insufficiency, Chronic - chemically induced</subject><subject>Renal Insufficiency, Chronic - complications</subject><subject>Renal Insufficiency, Chronic - metabolism</subject><subject>Severity of Illness Index</subject><subject>Studies</subject><subject>Telbivudine</subject><subject>Telbivudine - therapeutic use</subject><subject>Tenofovir</subject><subject>Tenofovir - adverse effects</subject><subject>Tenofovir - pharmacology</subject><subject>Transplant Surgery</subject><issn>0163-2116</issn><issn>1573-2568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kVFrFDEUhYNY7Lb6B3yQgM9Tb5KdZOdxXaotFFtK9TVkkps1ZTZZk5ml_nvTbmsRpOQh9ybfudzDIeQ9gxMGoD4VBpJDA6xroFVMNfCKzFirRMNbuXhNZsBkrRmTh-SolFsA6BSTb8ihYHwBooMZuTuP9EcYc6ImOvrQ7BK9xpi2OY1ox7BDeup9rQpNnt7g0Ifd5EJEGiJd_cwpBkvPcGvGMIZCP9OrWmGs-DVaDLsQ1_TbZAdMY3BIl9EMaT3hW3LgzVDw3eN9TL5_Ob1ZnTUXl1_PV8uLxs7nfGyYaGUHjEsUyts5zJ3nTiyENKZvveMGe7noe3DSK-7BG1k9GgCJzIDjShyTj_u51c-vCcuob9OU6xJFc95yxYTsxDO1NgPqEH0as7GbUKxeKsY70bYcKnXyH6oeh5tgU0Qf6vs_Ar4X2JxKyej1NoeNyb81A32fod5nqGuG-iFDfS_68Ljx1G_Q_ZU8hVYBsQdK_YprzM-WXhj7B_bBpaE</recordid><startdate>20191201</startdate><enddate>20191201</enddate><creator>Mak, Lung-Yi</creator><creator>Liu, Sze-Hang</creator><creator>Yap, Desmond Yat-Hin</creator><creator>Seto, Wai-Kay</creator><creator>Wong, Danny Ka-Ho</creator><creator>Fung, James</creator><creator>Chan, Tak-Mao</creator><creator>Lai, Ching-Lung</creator><creator>Yuen, Man-Fung</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>20191201</creationdate><title>In Vitro and In Vivo Renoprotective Effects of Telbivudine in Chronic Hepatitis B Patients Receiving Nucleotide Analogue</title><author>Mak, Lung-Yi ; Liu, Sze-Hang ; Yap, Desmond Yat-Hin ; Seto, Wai-Kay ; Wong, Danny Ka-Ho ; Fung, James ; Chan, Tak-Mao ; Lai, Ching-Lung ; Yuen, Man-Fung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-135690126e37fc404df2d3836aab5fd2aeb68bb0d6f72f0fa6097a006e1a0d273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Activating Transcription Factor 4 - drug effects</topic><topic>Activating Transcription Factor 4 - genetics</topic><topic>Adefovir dipivoxil</topic><topic>Adenine - adverse effects</topic><topic>Adenine - analogs & derivatives</topic><topic>Adenine - pharmacology</topic><topic>Analysis</topic><topic>Antiretroviral drugs</topic><topic>Antiviral Agents - pharmacology</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Antiviral drugs</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Biochemistry</topic><topic>Biomarkers</topic><topic>Caspase 12 - drug effects</topic><topic>Caspase 12 - genetics</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>Chronic kidney failure</topic><topic>Cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Endoplasmic Reticulum Chaperone BiP</topic><topic>Enzymes</topic><topic>Epithelial Cells</topic><topic>Female</topic><topic>Gastroenterology</topic><topic>Glomerular Filtration Rate</topic><topic>Heat-Shock Proteins - drug effects</topic><topic>Heat-Shock Proteins - genetics</topic><topic>Hepatitis</topic><topic>Hepatitis A Virus Cellular Receptor 1 - drug effects</topic><topic>Hepatitis A Virus Cellular Receptor 1 - genetics</topic><topic>Hepatitis B</topic><topic>Hepatitis B, Chronic - complications</topic><topic>Hepatitis B, Chronic - drug therapy</topic><topic>Hepatology</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Interferon</topic><topic>Interleukin-18 - genetics</topic><topic>Kidney diseases</topic><topic>Kidney Tubules</topic><topic>Lamivudine</topic><topic>Lamivudine - pharmacology</topic><topic>Lipocalin-2 - drug effects</topic><topic>Lipocalin-2 - genetics</topic><topic>Liver</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Medicine, Experimental</topic><topic>Middle Aged</topic><topic>Mitochondrial DNA</topic><topic>Mortality</topic><topic>Oncology</topic><topic>Organophosphonates - adverse effects</topic><topic>Organophosphonates - pharmacology</topic><topic>Original Article</topic><topic>Prospective Studies</topic><topic>Protective Agents</topic><topic>Renal Insufficiency, Chronic - chemically induced</topic><topic>Renal Insufficiency, Chronic - complications</topic><topic>Renal Insufficiency, Chronic - metabolism</topic><topic>Severity of Illness Index</topic><topic>Studies</topic><topic>Telbivudine</topic><topic>Telbivudine - therapeutic use</topic><topic>Tenofovir</topic><topic>Tenofovir - adverse effects</topic><topic>Tenofovir - pharmacology</topic><topic>Transplant Surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mak, Lung-Yi</creatorcontrib><creatorcontrib>Liu, Sze-Hang</creatorcontrib><creatorcontrib>Yap, Desmond Yat-Hin</creatorcontrib><creatorcontrib>Seto, Wai-Kay</creatorcontrib><creatorcontrib>Wong, Danny Ka-Ho</creatorcontrib><creatorcontrib>Fung, James</creatorcontrib><creatorcontrib>Chan, Tak-Mao</creatorcontrib><creatorcontrib>Lai, Ching-Lung</creatorcontrib><creatorcontrib>Yuen, Man-Fung</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><jtitle>Digestive diseases and sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mak, Lung-Yi</au><au>Liu, Sze-Hang</au><au>Yap, Desmond Yat-Hin</au><au>Seto, Wai-Kay</au><au>Wong, Danny Ka-Ho</au><au>Fung, James</au><au>Chan, Tak-Mao</au><au>Lai, Ching-Lung</au><au>Yuen, Man-Fung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In Vitro and In Vivo Renoprotective Effects of Telbivudine in Chronic Hepatitis B Patients Receiving Nucleotide Analogue</atitle><jtitle>Digestive diseases and sciences</jtitle><stitle>Dig Dis Sci</stitle><addtitle>Dig Dis Sci</addtitle><date>2019-12-01</date><risdate>2019</risdate><volume>64</volume><issue>12</issue><spage>3630</spage><epage>3641</epage><pages>3630-3641</pages><issn>0163-2116</issn><eissn>1573-2568</eissn><abstract>Aim
Renal toxicity of adefovir disoproxil (ADV) and tenofovir disoproxil fumarate (TDF) is a significant concern in chronic hepatitis B (CHB) patients. Early observational clinical data suggested that telbivudine (LdT) might have renoprotective effects.
Methods
In this prospective study, consecutive CHB patients on combined lamivudine (LAM) + ADV/TDF were switched to LdT + ADV/TDF at recruitment and were followed up for 24 months. Estimated glomerular filtration rate (eGFR) was calculated with the modification of diet in renal disease equation. The effects of LdT on cell viability and expression of kidney injury or apoptotic biomarkers were investigated in cultured renal tubular epithelial cell line HK-2.
Results
Thirty-one patients (median age 55 years, 90.3% male) were recruited (54.8% TDF: 45.2% ADV). Serum HBV DNA was undetectable at all time points. Median eGFR was 70.2 (IQR 62.6–77.9) and 81.5 (IQR 63.6–99.1) mL/min/1.73 m
2
at baseline and 24 months, respectively (
p
< 0.001). Downstaging of chronic kidney disease was observed in eight (25.8%) patients and was more common in ADV-treated compared to TDF-treated patients (7/8 vs. 1/17,
p
= 0.011; OR 16, 95% CI 1.643–155.766,
p
= 0.017). In vitro data showed that adding LdT to ADV or TDF was associated with improved cell viability and lower expression of injury and apoptotic biomarkers compared with ADV or TDF alone. Treatment was prematurely discontinued in four(12.9%) patients due to myalgia.
Conclusions
Clinical and in vitro data suggest that LdT has renoprotective effects in patients on long-term ADV/TDF treatment. LdT may be considered as an adjuvant therapy in this special group of patients with renal impairment (NCT03778567).</abstract><cop>New York</cop><pub>Springer US</pub><pmid>31280390</pmid><doi>10.1007/s10620-019-05717-0</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0163-2116 |
| ispartof | Digestive diseases and sciences, 2019-12, Vol.64 (12), p.3630-3641 |
| issn | 0163-2116 1573-2568 |
| language | eng |
| recordid | cdi_proquest_journals_2252713693 |
| source | MEDLINE; SpringerNature Complete Journals |
| subjects | Activating Transcription Factor 4 - drug effects Activating Transcription Factor 4 - genetics Adefovir dipivoxil Adenine - adverse effects Adenine - analogs & derivatives Adenine - pharmacology Analysis Antiretroviral drugs Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Antiviral drugs Apoptosis Apoptosis - drug effects Biochemistry Biomarkers Caspase 12 - drug effects Caspase 12 - genetics Cell Line Cell Survival - drug effects Chronic kidney failure Cytotoxicity Deoxyribonucleic acid DNA Endoplasmic Reticulum Chaperone BiP Enzymes Epithelial Cells Female Gastroenterology Glomerular Filtration Rate Heat-Shock Proteins - drug effects Heat-Shock Proteins - genetics Hepatitis Hepatitis A Virus Cellular Receptor 1 - drug effects Hepatitis A Virus Cellular Receptor 1 - genetics Hepatitis B Hepatitis B, Chronic - complications Hepatitis B, Chronic - drug therapy Hepatology Humans In Vitro Techniques Interferon Interleukin-18 - genetics Kidney diseases Kidney Tubules Lamivudine Lamivudine - pharmacology Lipocalin-2 - drug effects Lipocalin-2 - genetics Liver Male Medical research Medicine Medicine & Public Health Medicine, Experimental Middle Aged Mitochondrial DNA Mortality Oncology Organophosphonates - adverse effects Organophosphonates - pharmacology Original Article Prospective Studies Protective Agents Renal Insufficiency, Chronic - chemically induced Renal Insufficiency, Chronic - complications Renal Insufficiency, Chronic - metabolism Severity of Illness Index Studies Telbivudine Telbivudine - therapeutic use Tenofovir Tenofovir - adverse effects Tenofovir - pharmacology Transplant Surgery |
| title | In Vitro and In Vivo Renoprotective Effects of Telbivudine in Chronic Hepatitis B Patients Receiving Nucleotide Analogue |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T14%3A38%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=In%20Vitro%20and%20In%20Vivo%20Renoprotective%20Effects%20of%20Telbivudine%20in%20Chronic%20Hepatitis%20B%20Patients%20Receiving%20Nucleotide%20Analogue&rft.jtitle=Digestive%20diseases%20and%20sciences&rft.au=Mak,%20Lung-Yi&rft.date=2019-12-01&rft.volume=64&rft.issue=12&rft.spage=3630&rft.epage=3641&rft.pages=3630-3641&rft.issn=0163-2116&rft.eissn=1573-2568&rft_id=info:doi/10.1007/s10620-019-05717-0&rft_dat=%3Cgale_proqu%3EA712935520%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2252713693&rft_id=info:pmid/31280390&rft_galeid=A712935520&rfr_iscdi=true |