Does Monitoring Total and Free Polymyxin B1 Plasma Concentrations Predict Polymyxin B-Induced Nephrotoxicity? A Retrospective Study in Critically Ill Patients
Introduction The correlation between total and free polymyxin B (PMB including PMB1 and PMB2) exposure in vivo and acute kidney injury (AKI) remains obscure. This study explores the relationships between plasma exposure of PMB1 and PMB2 and nephrotoxicity, and investigates the risk factors for PMB-i...
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| description | Introduction
The correlation between total and free polymyxin B (PMB including PMB1 and PMB2) exposure in vivo and acute kidney injury (AKI) remains obscure. This study explores the relationships between plasma exposure of PMB1 and PMB2 and nephrotoxicity, and investigates the risk factors for PMB-induced acute kidney injury (AKI) in critically ill patients.
Methods
Critically ill patients who used PMB and met the criteria were enrolled. The total plasma concentration and plasma binding of PMB1 and PMB2 were analysed by liquid chromatography–tandem mass spectrometry and equilibrium dialysis.
Results
A total of 89 patients were finally included, and AKI developed in 28.1% of them. The peak concentration of PMB1 (
C
max
(B1)) (adjusted odds ratio (AOR) = 1.68, 95% CI 1.08–2.62,
p
= 0.023), baseline BUN level (AOR = 1.08, 95% CI 1.01–1.16,
p
= 0.039) and hypertension (AOR = 3.73, 95% CI 1.21–11.54,
p
= 0.022) were independent risk factors for PMB-induced AKI. The area under the ROC curve of the model was 0.799. When
C
max
(B1) was 5.23 μg/ml or more, the probability of AKI was higher than 50%. The ratio of PMB1/PMB2 decreased after PMB preparation entered into the body. The protein binding rate in critically ill patients indicated significant individual differences. Free
C
max
(B) and free
C
max
(B1) levels in the AKI group were significantly (
p
|
| doi_str_mv | 10.1007/s40121-022-00655-3 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9334479</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A711902304</galeid><sourcerecordid>A711902304</sourcerecordid><originalsourceid>FETCH-LOGICAL-c541t-fec2599b9e0517585d07cc377b0cb1e1f586ce013ac3515d0464fc2b94096fe83</originalsourceid><addsrcrecordid>eNp9ks1u1DAUhSMEolXpC7BAltiwSfFPEscbUBkojFRgBGVteZybqSvHHmynat6mz8KT4WGGlkEIeWHL97vn6tinKJ4SfEIw5i9jhQklJaa0xLip65I9KA4pEaxsWEsf7s4tpeKgOI7xCuPMtxUR_HFxwOqmFVyQw-L2rYeIPnpnkg_GrdCFT8oi5Tp0FgDQwttpmG6M-3H7hqCFVXFQaOadBpeCSsa7iBYBOqPTHlvOXTdq6NAnWF8Gn_yN0SZNr9Ep-gIp-LgGncw1oK9p7CZkHJoFk4xW1k5obi1aZPE8Iz4pHvXKRjje7UfFt7N3F7MP5fnn9_PZ6Xmp64qksgdNayGWAnBNeN3WHeZaM86XWC8JkL5uGw2YMKVZTXK1aqpe06WosGh6aNlR8Wqrux6XA3Rbf1augxlUmKRXRu5XnLmUK38tBWNVxUUWeLETCP77CDHJwUQN1ioHfoySNrxucMMrnNHnf6FXfgwu25O0bThhFLP6nlopC9K43ue5eiMqTzkhAlOGq0yd_IPKq4PBaO-gN_l-r4FuG3T-hRigv_NIsNxES26jJXO05K9oSZabnv35Onctv4OUAbYF4noTIwj3lv4j-xMtKdw0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2867132035</pqid></control><display><type>article</type><title>Does Monitoring Total and Free Polymyxin B1 Plasma Concentrations Predict Polymyxin B-Induced Nephrotoxicity? A Retrospective Study in Critically Ill Patients</title><source>DOAJ Directory of Open Access Journals</source><source>Springer Nature OA Free Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Deng, Yang ; Gu, Jun-Yuan ; Li, Xin ; Tong, Huan ; Guo, Si-Wei ; Xu, Bing ; Li, You ; Zhang, Bi-Kui ; Li, Ying ; Huang, Hai-Ying ; Xiao, Gui-Ying</creator><creatorcontrib>Deng, Yang ; Gu, Jun-Yuan ; Li, Xin ; Tong, Huan ; Guo, Si-Wei ; Xu, Bing ; Li, You ; Zhang, Bi-Kui ; Li, Ying ; Huang, Hai-Ying ; Xiao, Gui-Ying</creatorcontrib><description>Introduction
The correlation between total and free polymyxin B (PMB including PMB1 and PMB2) exposure in vivo and acute kidney injury (AKI) remains obscure. This study explores the relationships between plasma exposure of PMB1 and PMB2 and nephrotoxicity, and investigates the risk factors for PMB-induced acute kidney injury (AKI) in critically ill patients.
Methods
Critically ill patients who used PMB and met the criteria were enrolled. The total plasma concentration and plasma binding of PMB1 and PMB2 were analysed by liquid chromatography–tandem mass spectrometry and equilibrium dialysis.
Results
A total of 89 patients were finally included, and AKI developed in 28.1% of them. The peak concentration of PMB1 (
C
max
(B1)) (adjusted odds ratio (AOR) = 1.68, 95% CI 1.08–2.62,
p
= 0.023), baseline BUN level (AOR = 1.08, 95% CI 1.01–1.16,
p
= 0.039) and hypertension (AOR = 3.73, 95% CI 1.21–11.54,
p
= 0.022) were independent risk factors for PMB-induced AKI. The area under the ROC curve of the model was 0.799. When
C
max
(B1) was 5.23 μg/ml or more, the probability of AKI was higher than 50%. The ratio of PMB1/PMB2 decreased after PMB preparation entered into the body. The protein binding rate in critically ill patients indicated significant individual differences. Free
C
max
(B) and free
C
max
(B1) levels in the AKI group were significantly (
p
< 0.05) higher than those in the non-AKI group. Total and free concentrations of PMB in patients showed a positive correlation.
Conclusions
Both the ROC curve and logistic regression model showed that
C
max
(B1) was a good predictor for the probability of PMB-induced AKI. Early therapeutic drug monitoring (TDM) of PMB should be considered in critically ill patients. Compared with
C
min
(B),
C
max
(B) and
C
max
(B1) may be helpful for the early prediction of PMB-induced AKI in critically ill patients.</description><identifier>ISSN: 2193-8229</identifier><identifier>EISSN: 2193-6382</identifier><identifier>DOI: 10.1007/s40121-022-00655-3</identifier><identifier>PMID: 35689791</identifier><language>eng</language><publisher>Cheshire: Springer Healthcare</publisher><subject>Analysis ; Dialysis ; Hypertension ; Infectious Diseases ; Internal Medicine ; Kidneys ; Liquid chromatography ; Mass spectrometry ; Medical research ; Medicine ; Medicine & Public Health ; Medicine, Experimental ; Original Research ; Plasma ; Plasma physics ; Protein binding ; Risk factors</subject><ispartof>Infectious diseases and therapy, 2022-08, Vol.11 (4), p.1591-1608</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>COPYRIGHT 2022 Springer</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-fec2599b9e0517585d07cc377b0cb1e1f586ce013ac3515d0464fc2b94096fe83</citedby><cites>FETCH-LOGICAL-c541t-fec2599b9e0517585d07cc377b0cb1e1f586ce013ac3515d0464fc2b94096fe83</cites><orcidid>0000-0002-8866-6848</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/PMC9334479/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334479/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35689791$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Deng, Yang</creatorcontrib><creatorcontrib>Gu, Jun-Yuan</creatorcontrib><creatorcontrib>Li, Xin</creatorcontrib><creatorcontrib>Tong, Huan</creatorcontrib><creatorcontrib>Guo, Si-Wei</creatorcontrib><creatorcontrib>Xu, Bing</creatorcontrib><creatorcontrib>Li, You</creatorcontrib><creatorcontrib>Zhang, Bi-Kui</creatorcontrib><creatorcontrib>Li, Ying</creatorcontrib><creatorcontrib>Huang, Hai-Ying</creatorcontrib><creatorcontrib>Xiao, Gui-Ying</creatorcontrib><title>Does Monitoring Total and Free Polymyxin B1 Plasma Concentrations Predict Polymyxin B-Induced Nephrotoxicity? A Retrospective Study in Critically Ill Patients</title><title>Infectious diseases and therapy</title><addtitle>Infect Dis Ther</addtitle><addtitle>Infect Dis Ther</addtitle><description>Introduction
The correlation between total and free polymyxin B (PMB including PMB1 and PMB2) exposure in vivo and acute kidney injury (AKI) remains obscure. This study explores the relationships between plasma exposure of PMB1 and PMB2 and nephrotoxicity, and investigates the risk factors for PMB-induced acute kidney injury (AKI) in critically ill patients.
Methods
Critically ill patients who used PMB and met the criteria were enrolled. The total plasma concentration and plasma binding of PMB1 and PMB2 were analysed by liquid chromatography–tandem mass spectrometry and equilibrium dialysis.
Results
A total of 89 patients were finally included, and AKI developed in 28.1% of them. The peak concentration of PMB1 (
C
max
(B1)) (adjusted odds ratio (AOR) = 1.68, 95% CI 1.08–2.62,
p
= 0.023), baseline BUN level (AOR = 1.08, 95% CI 1.01–1.16,
p
= 0.039) and hypertension (AOR = 3.73, 95% CI 1.21–11.54,
p
= 0.022) were independent risk factors for PMB-induced AKI. The area under the ROC curve of the model was 0.799. When
C
max
(B1) was 5.23 μg/ml or more, the probability of AKI was higher than 50%. The ratio of PMB1/PMB2 decreased after PMB preparation entered into the body. The protein binding rate in critically ill patients indicated significant individual differences. Free
C
max
(B) and free
C
max
(B1) levels in the AKI group were significantly (
p
< 0.05) higher than those in the non-AKI group. Total and free concentrations of PMB in patients showed a positive correlation.
Conclusions
Both the ROC curve and logistic regression model showed that
C
max
(B1) was a good predictor for the probability of PMB-induced AKI. Early therapeutic drug monitoring (TDM) of PMB should be considered in critically ill patients. Compared with
C
min
(B),
C
max
(B) and
C
max
(B1) may be helpful for the early prediction of PMB-induced AKI in critically ill patients.</description><subject>Analysis</subject><subject>Dialysis</subject><subject>Hypertension</subject><subject>Infectious Diseases</subject><subject>Internal Medicine</subject><subject>Kidneys</subject><subject>Liquid chromatography</subject><subject>Mass spectrometry</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Medicine, Experimental</subject><subject>Original Research</subject><subject>Plasma</subject><subject>Plasma physics</subject><subject>Protein binding</subject><subject>Risk factors</subject><issn>2193-8229</issn><issn>2193-6382</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNp9ks1u1DAUhSMEolXpC7BAltiwSfFPEscbUBkojFRgBGVteZybqSvHHmynat6mz8KT4WGGlkEIeWHL97vn6tinKJ4SfEIw5i9jhQklJaa0xLip65I9KA4pEaxsWEsf7s4tpeKgOI7xCuPMtxUR_HFxwOqmFVyQw-L2rYeIPnpnkg_GrdCFT8oi5Tp0FgDQwttpmG6M-3H7hqCFVXFQaOadBpeCSsa7iBYBOqPTHlvOXTdq6NAnWF8Gn_yN0SZNr9Ep-gIp-LgGncw1oK9p7CZkHJoFk4xW1k5obi1aZPE8Iz4pHvXKRjje7UfFt7N3F7MP5fnn9_PZ6Xmp64qksgdNayGWAnBNeN3WHeZaM86XWC8JkL5uGw2YMKVZTXK1aqpe06WosGh6aNlR8Wqrux6XA3Rbf1augxlUmKRXRu5XnLmUK38tBWNVxUUWeLETCP77CDHJwUQN1ioHfoySNrxucMMrnNHnf6FXfgwu25O0bThhFLP6nlopC9K43ue5eiMqTzkhAlOGq0yd_IPKq4PBaO-gN_l-r4FuG3T-hRigv_NIsNxES26jJXO05K9oSZabnv35Onctv4OUAbYF4noTIwj3lv4j-xMtKdw0</recordid><startdate>20220801</startdate><enddate>20220801</enddate><creator>Deng, Yang</creator><creator>Gu, Jun-Yuan</creator><creator>Li, Xin</creator><creator>Tong, Huan</creator><creator>Guo, Si-Wei</creator><creator>Xu, Bing</creator><creator>Li, You</creator><creator>Zhang, Bi-Kui</creator><creator>Li, Ying</creator><creator>Huang, Hai-Ying</creator><creator>Xiao, Gui-Ying</creator><general>Springer Healthcare</general><general>Springer</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>8AO</scope><scope>8C1</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>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8866-6848</orcidid></search><sort><creationdate>20220801</creationdate><title>Does Monitoring Total and Free Polymyxin B1 Plasma Concentrations Predict Polymyxin B-Induced Nephrotoxicity? A Retrospective Study in Critically Ill Patients</title><author>Deng, Yang ; Gu, Jun-Yuan ; Li, Xin ; Tong, Huan ; Guo, Si-Wei ; Xu, Bing ; Li, You ; Zhang, Bi-Kui ; Li, Ying ; Huang, Hai-Ying ; Xiao, Gui-Ying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c541t-fec2599b9e0517585d07cc377b0cb1e1f586ce013ac3515d0464fc2b94096fe83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Analysis</topic><topic>Dialysis</topic><topic>Hypertension</topic><topic>Infectious Diseases</topic><topic>Internal Medicine</topic><topic>Kidneys</topic><topic>Liquid chromatography</topic><topic>Mass spectrometry</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Medicine, Experimental</topic><topic>Original Research</topic><topic>Plasma</topic><topic>Plasma physics</topic><topic>Protein binding</topic><topic>Risk factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Deng, Yang</creatorcontrib><creatorcontrib>Gu, Jun-Yuan</creatorcontrib><creatorcontrib>Li, Xin</creatorcontrib><creatorcontrib>Tong, Huan</creatorcontrib><creatorcontrib>Guo, Si-Wei</creatorcontrib><creatorcontrib>Xu, Bing</creatorcontrib><creatorcontrib>Li, You</creatorcontrib><creatorcontrib>Zhang, Bi-Kui</creatorcontrib><creatorcontrib>Li, Ying</creatorcontrib><creatorcontrib>Huang, Hai-Ying</creatorcontrib><creatorcontrib>Xiao, Gui-Ying</creatorcontrib><collection>Springer Nature OA Free Journals</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>ProQuest Pharma Collection</collection><collection>Public Health Database</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>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Nursing & Allied Health Premium</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Infectious diseases and therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Deng, Yang</au><au>Gu, Jun-Yuan</au><au>Li, Xin</au><au>Tong, Huan</au><au>Guo, Si-Wei</au><au>Xu, Bing</au><au>Li, You</au><au>Zhang, Bi-Kui</au><au>Li, Ying</au><au>Huang, Hai-Ying</au><au>Xiao, Gui-Ying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Does Monitoring Total and Free Polymyxin B1 Plasma Concentrations Predict Polymyxin B-Induced Nephrotoxicity? A Retrospective Study in Critically Ill Patients</atitle><jtitle>Infectious diseases and therapy</jtitle><stitle>Infect Dis Ther</stitle><addtitle>Infect Dis Ther</addtitle><date>2022-08-01</date><risdate>2022</risdate><volume>11</volume><issue>4</issue><spage>1591</spage><epage>1608</epage><pages>1591-1608</pages><issn>2193-8229</issn><eissn>2193-6382</eissn><abstract>Introduction
The correlation between total and free polymyxin B (PMB including PMB1 and PMB2) exposure in vivo and acute kidney injury (AKI) remains obscure. This study explores the relationships between plasma exposure of PMB1 and PMB2 and nephrotoxicity, and investigates the risk factors for PMB-induced acute kidney injury (AKI) in critically ill patients.
Methods
Critically ill patients who used PMB and met the criteria were enrolled. The total plasma concentration and plasma binding of PMB1 and PMB2 were analysed by liquid chromatography–tandem mass spectrometry and equilibrium dialysis.
Results
A total of 89 patients were finally included, and AKI developed in 28.1% of them. The peak concentration of PMB1 (
C
max
(B1)) (adjusted odds ratio (AOR) = 1.68, 95% CI 1.08–2.62,
p
= 0.023), baseline BUN level (AOR = 1.08, 95% CI 1.01–1.16,
p
= 0.039) and hypertension (AOR = 3.73, 95% CI 1.21–11.54,
p
= 0.022) were independent risk factors for PMB-induced AKI. The area under the ROC curve of the model was 0.799. When
C
max
(B1) was 5.23 μg/ml or more, the probability of AKI was higher than 50%. The ratio of PMB1/PMB2 decreased after PMB preparation entered into the body. The protein binding rate in critically ill patients indicated significant individual differences. Free
C
max
(B) and free
C
max
(B1) levels in the AKI group were significantly (
p
< 0.05) higher than those in the non-AKI group. Total and free concentrations of PMB in patients showed a positive correlation.
Conclusions
Both the ROC curve and logistic regression model showed that
C
max
(B1) was a good predictor for the probability of PMB-induced AKI. Early therapeutic drug monitoring (TDM) of PMB should be considered in critically ill patients. Compared with
C
min
(B),
C
max
(B) and
C
max
(B1) may be helpful for the early prediction of PMB-induced AKI in critically ill patients.</abstract><cop>Cheshire</cop><pub>Springer Healthcare</pub><pmid>35689791</pmid><doi>10.1007/s40121-022-00655-3</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-8866-6848</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2193-8229 |
| ispartof | Infectious diseases and therapy, 2022-08, Vol.11 (4), p.1591-1608 |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9334479 |
| source | DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Analysis Dialysis Hypertension Infectious Diseases Internal Medicine Kidneys Liquid chromatography Mass spectrometry Medical research Medicine Medicine & Public Health Medicine, Experimental Original Research Plasma Plasma physics Protein binding Risk factors |
| title | Does Monitoring Total and Free Polymyxin B1 Plasma Concentrations Predict Polymyxin B-Induced Nephrotoxicity? A Retrospective Study in Critically Ill Patients |
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