Association of Urine Platinum With Acute Kidney Injury in Children Treated With Cisplatin for Cancer
Cisplatin is a chemotherapeutic agent highly excreted in urine and known to cause acute kidney injury (AKI). As AKI diagnosis by serum creatinine (SCr) is usually delayed, endeavors for finding early AKI biomarkers continue. This study aims to determine if urine platinum (UP) concentration 24 hours...
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Veröffentlicht in: | Journal of clinical pharmacology 2021-07, Vol.61 (7), p.871-880 |
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creator | Lebel, Asaf Chui, Hayton McMahon, Kelly R. Lim, Yong Jin Macri, Joseph Wang, Stella Devarajan, Prasad Blydt‐Hansen, Tom D. Zappitelli, Michael Urquhart, Bradley L. |
description | Cisplatin is a chemotherapeutic agent highly excreted in urine and known to cause acute kidney injury (AKI). As AKI diagnosis by serum creatinine (SCr) is usually delayed, endeavors for finding early AKI biomarkers continue. This study aims to determine if urine platinum (UP) concentration 24 hours after cisplatin infusion is associated with AKI, and to evaluate the association between urine platinum and tubular damage biomarkers: neutrophil gelatinase‐associated lipocalin (NGAL) and kidney injury molecule‐1 (KIM‐1). Children treated with cisplatin in 12 Canadian centers (April 2013 to December 2017) were included. Urine from the morning after the first cisplatin infusion of the first or second cisplatin cycle was measured for urine platinum, NGAL, and KIM‐1. SCr and serum electrolytes were used to detect AKI by either SCr elevation or urinary electrolyte wasting (potassium, magnesium, phosphate). The associations of urine platinum with AKI, NGAL, and KIM‐1 were assessed. A total of 115 participants (54% boys, median age, 8.5 years; interquartile range, 4.0‐13.4) were included, of which 29 (25%) and 105 (91%) developed AKI defined by SCr and electrolyte criteria, respectively. Higher urine platinum was associated with higher cisplatin dose (Spearman rho, 0.21) and with younger age (Spearman rho, –0.33). Urine platinum was not associated with postinfusion AKIor KIM‐1, but was weakly associated with NGAL, particularly in participants without SCr AKI (Pearson's r, 0.22). Urine platinum may be a marker of mild tubular injury but is not likely to be a useful biomarker of clinically evident AKI. |
doi_str_mv | 10.1002/jcph.1839 |
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As AKI diagnosis by serum creatinine (SCr) is usually delayed, endeavors for finding early AKI biomarkers continue. This study aims to determine if urine platinum (UP) concentration 24 hours after cisplatin infusion is associated with AKI, and to evaluate the association between urine platinum and tubular damage biomarkers: neutrophil gelatinase‐associated lipocalin (NGAL) and kidney injury molecule‐1 (KIM‐1). Children treated with cisplatin in 12 Canadian centers (April 2013 to December 2017) were included. Urine from the morning after the first cisplatin infusion of the first or second cisplatin cycle was measured for urine platinum, NGAL, and KIM‐1. SCr and serum electrolytes were used to detect AKI by either SCr elevation or urinary electrolyte wasting (potassium, magnesium, phosphate). The associations of urine platinum with AKI, NGAL, and KIM‐1 were assessed. A total of 115 participants (54% boys, median age, 8.5 years; interquartile range, 4.0‐13.4) were included, of which 29 (25%) and 105 (91%) developed AKI defined by SCr and electrolyte criteria, respectively. Higher urine platinum was associated with higher cisplatin dose (Spearman rho, 0.21) and with younger age (Spearman rho, –0.33). Urine platinum was not associated with postinfusion AKIor KIM‐1, but was weakly associated with NGAL, particularly in participants without SCr AKI (Pearson's r, 0.22). Urine platinum may be a marker of mild tubular injury but is not likely to be a useful biomarker of clinically evident AKI.</description><identifier>ISSN: 0091-2700</identifier><identifier>EISSN: 1552-4604</identifier><identifier>DOI: 10.1002/jcph.1839</identifier><identifier>PMID: 33599997</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>acute kidney injury ; Acute Kidney Injury - diagnosis ; Antineoplastic Agents - therapeutic use ; Antineoplastic Agents - urine ; Biomarkers ; Chemotherapy ; Child ; Child, Preschool ; Children ; Cisplatin ; Cisplatin - therapeutic use ; Cisplatin - urine ; Creatinine ; Dose-Response Relationship, Drug ; Electrolytes ; Electrolytes - urine ; Female ; Gelatinase ; Hepatitis A Virus Cellular Receptor 1 - metabolism ; Humans ; Kidney Function Tests ; Kidneys ; Leukocytes (neutrophilic) ; Lipocalin ; Lipocalin-2 - urine ; Magnesium ; Male ; Neoplasms - drug therapy ; Platinum ; Platinum - urine ; Urine ; urine platinum</subject><ispartof>Journal of clinical pharmacology, 2021-07, Vol.61 (7), p.871-880</ispartof><rights>2021, The American College of Clinical Pharmacology</rights><rights>2021, The American College of Clinical Pharmacology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4439-d6836d82850015770e2d617c16bd6cb6c6eec73ce3a575e235ae8b821af8f6e43</citedby><cites>FETCH-LOGICAL-c4439-d6836d82850015770e2d617c16bd6cb6c6eec73ce3a575e235ae8b821af8f6e43</cites><orcidid>0000-0001-7278-3137</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcph.1839$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcph.1839$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33599997$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lebel, Asaf</creatorcontrib><creatorcontrib>Chui, Hayton</creatorcontrib><creatorcontrib>McMahon, Kelly R.</creatorcontrib><creatorcontrib>Lim, Yong Jin</creatorcontrib><creatorcontrib>Macri, Joseph</creatorcontrib><creatorcontrib>Wang, Stella</creatorcontrib><creatorcontrib>Devarajan, Prasad</creatorcontrib><creatorcontrib>Blydt‐Hansen, Tom D.</creatorcontrib><creatorcontrib>Zappitelli, Michael</creatorcontrib><creatorcontrib>Urquhart, Bradley L.</creatorcontrib><title>Association of Urine Platinum With Acute Kidney Injury in Children Treated With Cisplatin for Cancer</title><title>Journal of clinical pharmacology</title><addtitle>J Clin Pharmacol</addtitle><description>Cisplatin is a chemotherapeutic agent highly excreted in urine and known to cause acute kidney injury (AKI). As AKI diagnosis by serum creatinine (SCr) is usually delayed, endeavors for finding early AKI biomarkers continue. This study aims to determine if urine platinum (UP) concentration 24 hours after cisplatin infusion is associated with AKI, and to evaluate the association between urine platinum and tubular damage biomarkers: neutrophil gelatinase‐associated lipocalin (NGAL) and kidney injury molecule‐1 (KIM‐1). Children treated with cisplatin in 12 Canadian centers (April 2013 to December 2017) were included. Urine from the morning after the first cisplatin infusion of the first or second cisplatin cycle was measured for urine platinum, NGAL, and KIM‐1. SCr and serum electrolytes were used to detect AKI by either SCr elevation or urinary electrolyte wasting (potassium, magnesium, phosphate). The associations of urine platinum with AKI, NGAL, and KIM‐1 were assessed. A total of 115 participants (54% boys, median age, 8.5 years; interquartile range, 4.0‐13.4) were included, of which 29 (25%) and 105 (91%) developed AKI defined by SCr and electrolyte criteria, respectively. Higher urine platinum was associated with higher cisplatin dose (Spearman rho, 0.21) and with younger age (Spearman rho, –0.33). Urine platinum was not associated with postinfusion AKIor KIM‐1, but was weakly associated with NGAL, particularly in participants without SCr AKI (Pearson's r, 0.22). Urine platinum may be a marker of mild tubular injury but is not likely to be a useful biomarker of clinically evident AKI.</description><subject>acute kidney injury</subject><subject>Acute Kidney Injury - diagnosis</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antineoplastic Agents - urine</subject><subject>Biomarkers</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Cisplatin</subject><subject>Cisplatin - therapeutic use</subject><subject>Cisplatin - urine</subject><subject>Creatinine</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electrolytes</subject><subject>Electrolytes - urine</subject><subject>Female</subject><subject>Gelatinase</subject><subject>Hepatitis A Virus Cellular Receptor 1 - metabolism</subject><subject>Humans</subject><subject>Kidney Function Tests</subject><subject>Kidneys</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lipocalin</subject><subject>Lipocalin-2 - urine</subject><subject>Magnesium</subject><subject>Male</subject><subject>Neoplasms - drug therapy</subject><subject>Platinum</subject><subject>Platinum - urine</subject><subject>Urine</subject><subject>urine platinum</subject><issn>0091-2700</issn><issn>1552-4604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU9r2zAYh8XoWNJuh32BIuhpBzf6Y8n2ZRBM27QrLIeEHYUivW4UHCmT7I58-zpNF7rDdBHoffS8P_gh9JWSa0oIm2zMbn1NS159QGMqBMtySfIzNCakohkrCBmh85Q2hFCZC_oJjTgX1XCKMbLTlIJxunPB49DgZXQe8LwdHny_xb9ct8ZT03eAfzjrYY_v_aaPe-w8rteutRE8XkTQHdgjXLu0e_2NmxBxrb2B-Bl9bHSb4MvbfYGWtzeLepY9_ry7r6ePmclzXmVWllzakpViSCqKggCzkhaGypWVZiWNBDAFN8C1KAQwLjSUq5JR3ZSNhJxfoO9H765fbcEa8F3UrdpFt9Vxr4J26t-Jd2v1FJ7VsJPLigyCqzdBDL97SJ3ahD76IbNiIme5pBU_UN-OlIkhpQjNaQMl6lCIOhSiDoUM7OX7SCfybwMDMDkCf1wL-_-b1EM9n70qXwD7RZaN</recordid><startdate>202107</startdate><enddate>202107</enddate><creator>Lebel, Asaf</creator><creator>Chui, Hayton</creator><creator>McMahon, Kelly R.</creator><creator>Lim, Yong Jin</creator><creator>Macri, Joseph</creator><creator>Wang, Stella</creator><creator>Devarajan, Prasad</creator><creator>Blydt‐Hansen, Tom D.</creator><creator>Zappitelli, Michael</creator><creator>Urquhart, Bradley L.</creator><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7278-3137</orcidid></search><sort><creationdate>202107</creationdate><title>Association of Urine Platinum With Acute Kidney Injury in Children Treated With Cisplatin for Cancer</title><author>Lebel, Asaf ; 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As AKI diagnosis by serum creatinine (SCr) is usually delayed, endeavors for finding early AKI biomarkers continue. This study aims to determine if urine platinum (UP) concentration 24 hours after cisplatin infusion is associated with AKI, and to evaluate the association between urine platinum and tubular damage biomarkers: neutrophil gelatinase‐associated lipocalin (NGAL) and kidney injury molecule‐1 (KIM‐1). Children treated with cisplatin in 12 Canadian centers (April 2013 to December 2017) were included. Urine from the morning after the first cisplatin infusion of the first or second cisplatin cycle was measured for urine platinum, NGAL, and KIM‐1. SCr and serum electrolytes were used to detect AKI by either SCr elevation or urinary electrolyte wasting (potassium, magnesium, phosphate). The associations of urine platinum with AKI, NGAL, and KIM‐1 were assessed. A total of 115 participants (54% boys, median age, 8.5 years; interquartile range, 4.0‐13.4) were included, of which 29 (25%) and 105 (91%) developed AKI defined by SCr and electrolyte criteria, respectively. Higher urine platinum was associated with higher cisplatin dose (Spearman rho, 0.21) and with younger age (Spearman rho, –0.33). Urine platinum was not associated with postinfusion AKIor KIM‐1, but was weakly associated with NGAL, particularly in participants without SCr AKI (Pearson's r, 0.22). Urine platinum may be a marker of mild tubular injury but is not likely to be a useful biomarker of clinically evident AKI.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33599997</pmid><doi>10.1002/jcph.1839</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-7278-3137</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | acute kidney injury Acute Kidney Injury - diagnosis Antineoplastic Agents - therapeutic use Antineoplastic Agents - urine Biomarkers Chemotherapy Child Child, Preschool Children Cisplatin Cisplatin - therapeutic use Cisplatin - urine Creatinine Dose-Response Relationship, Drug Electrolytes Electrolytes - urine Female Gelatinase Hepatitis A Virus Cellular Receptor 1 - metabolism Humans Kidney Function Tests Kidneys Leukocytes (neutrophilic) Lipocalin Lipocalin-2 - urine Magnesium Male Neoplasms - drug therapy Platinum Platinum - urine Urine urine platinum |
title | Association of Urine Platinum With Acute Kidney Injury in Children Treated With Cisplatin for Cancer |
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