The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study
Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs. We investigated the asso...
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| Veröffentlicht in: | PLoS medicine 2020-06, Vol.17 (6), p.e1003140 |
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| creator | Douwes, Rianne M Gomes-Neto, António W Eisenga, Michele F Van Loon, Elisabet Schutten, Joëlle C Gans, Rijk O B Naesens, Maarten van den Berg, Else Sprangers, Ben Berger, Stefan P Navis, Gerjan Blokzijl, Hans Meijers, Björn Bakker, Stephan J L Kuypers, Dirk |
| description | Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs.
We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21-2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation.
We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs.
ClinicalTrials.gov Identifier: NCT02811835, NCT01331668. |
| doi_str_mv | 10.1371/journal.pmed.1003140 |
| format | Article |
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We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21-2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation.
We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs.
ClinicalTrials.gov Identifier: NCT02811835, NCT01331668.</description><identifier>ISSN: 1549-1676</identifier><identifier>ISSN: 1549-1277</identifier><identifier>EISSN: 1549-1676</identifier><identifier>DOI: 10.1371/journal.pmed.1003140</identifier><identifier>PMID: 32542023</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Ambulatory care facilities ; Biobanks ; Biology and Life Sciences ; Cohort analysis ; Dosage ; Dose-Response Relationship, Drug ; Drug dosages ; Female ; Funding ; Health aspects ; Hospitals ; Humans ; Immunology ; Internal medicine ; Kaplan-Meier Estimate ; Kidney transplantation ; Kidney Transplantation - mortality ; Kidney transplants ; Kidneys ; Male ; Medical centers ; Medicine ; Medicine and Health Sciences ; Middle Aged ; Mortality ; Nephrology ; Nutrition ; Omeprazole ; Organ transplant recipients ; Physical Sciences ; Proportional Hazards Models ; Prospective Studies ; Proton pump inhibitors ; Proton Pump Inhibitors - adverse effects ; Proton Pump Inhibitors - therapeutic use ; Regression analysis ; Risk Factors ; Supervision</subject><ispartof>PLoS medicine, 2020-06, Vol.17 (6), p.e1003140</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Douwes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Douwes et al 2020 Douwes et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c764t-7fb095f8dc83ae29776aa860d91769712062c55bc9b50598ad875a8050f53dd13</citedby><cites>FETCH-LOGICAL-c764t-7fb095f8dc83ae29776aa860d91769712062c55bc9b50598ad875a8050f53dd13</cites><orcidid>0000-0002-4398-4877 ; 0000-0002-2846-2026 ; 0000-0003-3356-6791 ; 0000-0002-2484-6233 ; 0000-0002-2517-5769 ; 0000-0003-4240-7506 ; 0000-0003-2228-4676 ; 0000-0002-5625-0792 ; 0000-0001-9796-9157 ; 0000-0003-3349-0045</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295199/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295199/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32542023$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Taal, Maarten W.</contributor><creatorcontrib>Douwes, Rianne M</creatorcontrib><creatorcontrib>Gomes-Neto, António W</creatorcontrib><creatorcontrib>Eisenga, Michele F</creatorcontrib><creatorcontrib>Van Loon, Elisabet</creatorcontrib><creatorcontrib>Schutten, Joëlle C</creatorcontrib><creatorcontrib>Gans, Rijk O B</creatorcontrib><creatorcontrib>Naesens, Maarten</creatorcontrib><creatorcontrib>van den Berg, Else</creatorcontrib><creatorcontrib>Sprangers, Ben</creatorcontrib><creatorcontrib>Berger, Stefan P</creatorcontrib><creatorcontrib>Navis, Gerjan</creatorcontrib><creatorcontrib>Blokzijl, Hans</creatorcontrib><creatorcontrib>Meijers, Björn</creatorcontrib><creatorcontrib>Bakker, Stephan J L</creatorcontrib><creatorcontrib>Kuypers, Dirk</creatorcontrib><title>The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study</title><title>PLoS medicine</title><addtitle>PLoS Med</addtitle><description>Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs.
We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21-2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation.
We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs.
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mortality</topic><topic>Kidney transplants</topic><topic>Kidneys</topic><topic>Male</topic><topic>Medical centers</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Nephrology</topic><topic>Nutrition</topic><topic>Omeprazole</topic><topic>Organ transplant recipients</topic><topic>Physical Sciences</topic><topic>Proportional Hazards Models</topic><topic>Prospective Studies</topic><topic>Proton pump inhibitors</topic><topic>Proton Pump Inhibitors - adverse effects</topic><topic>Proton Pump Inhibitors - therapeutic use</topic><topic>Regression analysis</topic><topic>Risk Factors</topic><topic>Supervision</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Douwes, Rianne M</creatorcontrib><creatorcontrib>Gomes-Neto, António W</creatorcontrib><creatorcontrib>Eisenga, Michele F</creatorcontrib><creatorcontrib>Van Loon, Elisabet</creatorcontrib><creatorcontrib>Schutten, Joëlle C</creatorcontrib><creatorcontrib>Gans, Rijk O B</creatorcontrib><creatorcontrib>Naesens, Maarten</creatorcontrib><creatorcontrib>van den Berg, Else</creatorcontrib><creatorcontrib>Sprangers, Ben</creatorcontrib><creatorcontrib>Berger, Stefan P</creatorcontrib><creatorcontrib>Navis, Gerjan</creatorcontrib><creatorcontrib>Blokzijl, Hans</creatorcontrib><creatorcontrib>Meijers, Björn</creatorcontrib><creatorcontrib>Bakker, Stephan J L</creatorcontrib><creatorcontrib>Kuypers, Dirk</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Medicine</collection><jtitle>PLoS medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Douwes, Rianne M</au><au>Gomes-Neto, António W</au><au>Eisenga, Michele F</au><au>Van Loon, Elisabet</au><au>Schutten, Joëlle C</au><au>Gans, Rijk O B</au><au>Naesens, Maarten</au><au>van den Berg, Else</au><au>Sprangers, Ben</au><au>Berger, Stefan P</au><au>Navis, Gerjan</au><au>Blokzijl, Hans</au><au>Meijers, Björn</au><au>Bakker, Stephan J L</au><au>Kuypers, Dirk</au><au>Taal, Maarten W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study</atitle><jtitle>PLoS medicine</jtitle><addtitle>PLoS Med</addtitle><date>2020-06-15</date><risdate>2020</risdate><volume>17</volume><issue>6</issue><spage>e1003140</spage><pages>e1003140-</pages><issn>1549-1676</issn><issn>1549-1277</issn><eissn>1549-1676</eissn><abstract>Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs.
We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21-2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation.
We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs.
ClinicalTrials.gov Identifier: NCT02811835, NCT01331668.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32542023</pmid><doi>10.1371/journal.pmed.1003140</doi><orcidid>https://orcid.org/0000-0002-4398-4877</orcidid><orcidid>https://orcid.org/0000-0002-2846-2026</orcidid><orcidid>https://orcid.org/0000-0003-3356-6791</orcidid><orcidid>https://orcid.org/0000-0002-2484-6233</orcidid><orcidid>https://orcid.org/0000-0002-2517-5769</orcidid><orcidid>https://orcid.org/0000-0003-4240-7506</orcidid><orcidid>https://orcid.org/0000-0003-2228-4676</orcidid><orcidid>https://orcid.org/0000-0002-5625-0792</orcidid><orcidid>https://orcid.org/0000-0001-9796-9157</orcidid><orcidid>https://orcid.org/0000-0003-3349-0045</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1549-1676 |
| ispartof | PLoS medicine, 2020-06, Vol.17 (6), p.e1003140 |
| issn | 1549-1676 1549-1277 1549-1676 |
| language | eng |
| recordid | cdi_plos_journals_2460800745 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Ambulatory care facilities Biobanks Biology and Life Sciences Cohort analysis Dosage Dose-Response Relationship, Drug Drug dosages Female Funding Health aspects Hospitals Humans Immunology Internal medicine Kaplan-Meier Estimate Kidney transplantation Kidney Transplantation - mortality Kidney transplants Kidneys Male Medical centers Medicine Medicine and Health Sciences Middle Aged Mortality Nephrology Nutrition Omeprazole Organ transplant recipients Physical Sciences Proportional Hazards Models Prospective Studies Proton pump inhibitors Proton Pump Inhibitors - adverse effects Proton Pump Inhibitors - therapeutic use Regression analysis Risk Factors Supervision |
| title | The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T19%3A01%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20association%20between%20use%20of%20proton-pump%20inhibitors%20and%20excess%20mortality%20after%20kidney%20transplantation:%20A%20cohort%20study&rft.jtitle=PLoS%20medicine&rft.au=Douwes,%20Rianne%20M&rft.date=2020-06-15&rft.volume=17&rft.issue=6&rft.spage=e1003140&rft.pages=e1003140-&rft.issn=1549-1676&rft.eissn=1549-1676&rft_id=info:doi/10.1371/journal.pmed.1003140&rft_dat=%3Cgale_plos_%3EA632950594%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2460800745&rft_id=info:pmid/32542023&rft_galeid=A632950594&rft_doaj_id=oai_doaj_org_article_53440aedf8774e7196737f6cbe00ca6c&rfr_iscdi=true |