Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine
Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine. We explored the hypothesis that measurements of mRNA encoding interferon-inducible protein-10 (IP-10) or the chemokine receptor CXCR3 in urinary cells offer a noninvasive means of elucidating...
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| Veröffentlicht in: | Kidney international 2004-06, Vol.65 (6), p.2390-2397 |
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| creator | Tatapudi, Ravi Raju Muthukumar, Thangamani Dadhania, Darshana Ding, Ruchuang Li, Baogui Sharma, Vijay K. Lozada-Pastorio, Elizabeth Seetharamu, Nagashree Hartono, Choli Serur, David Seshan, Surya V. Kapur, Sandip Hancock, Wayne W. Suthanthiran, Manikkam |
| description | Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine.
We explored the hypothesis that measurements of mRNA encoding interferon-inducible protein-10 (IP-10) or the chemokine receptor CXCR3 in urinary cells offer a noninvasive means of elucidating cellular traffic causing acute rejection of human renal allografts.
We obtained 63 urine specimens from 58 renal allograft recipients who underwent 63 allograft biopsies to resolve the basis for graft dysfunction, and 27 additional urine samples from 24 other patients with stable allograft function. Twenty-seven of the 63 biopsies were classified as acute rejection, 20 as other, and 16 as chronic allograft nephropathy. We measured the levels of transcripts for IP-10 and CXCR3, and a constitutively expressed gene 18S rRNA in the urine specimens and correlated transcript levels with renal allograft diagnosis.
mRNA levels of IP-10 (P < 0.0001) or CXCR3 (P < 0.0001) but not the levels of 18S rRNA (P = 0.56) predicted intragraft cellular traffic causing acute rejection. Receiver-operating characteristic curve analysis demonstrated that acute rejection can be predicted with a sensitivity of 100% and a specificity of 78% using the (log-transformed) cutoff value of 9.11 copies of IP-10, and with a sensitivity of 63% and a specificity of 83% using the cutoff value of 11.59 copies of CXCR3. Immunohistologic analysis of allograft biopsies showed exuberant expression of IP-10 and CXCR3 during acute rejection whereas both were absent in grafts with stable function.
Our investigation demonstrates that intragraft cellular events associated with acute rejection of human renal allografts can be noninvasively identified by measurements of mRNA for IP-10 and CXCR3 in urinary cells. |
| doi_str_mv | 10.1111/j.1523-1755.2004.00663.x |
| format | Article |
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We explored the hypothesis that measurements of mRNA encoding interferon-inducible protein-10 (IP-10) or the chemokine receptor CXCR3 in urinary cells offer a noninvasive means of elucidating cellular traffic causing acute rejection of human renal allografts.
We obtained 63 urine specimens from 58 renal allograft recipients who underwent 63 allograft biopsies to resolve the basis for graft dysfunction, and 27 additional urine samples from 24 other patients with stable allograft function. Twenty-seven of the 63 biopsies were classified as acute rejection, 20 as other, and 16 as chronic allograft nephropathy. We measured the levels of transcripts for IP-10 and CXCR3, and a constitutively expressed gene 18S rRNA in the urine specimens and correlated transcript levels with renal allograft diagnosis.
mRNA levels of IP-10 (P < 0.0001) or CXCR3 (P < 0.0001) but not the levels of 18S rRNA (P = 0.56) predicted intragraft cellular traffic causing acute rejection. Receiver-operating characteristic curve analysis demonstrated that acute rejection can be predicted with a sensitivity of 100% and a specificity of 78% using the (log-transformed) cutoff value of 9.11 copies of IP-10, and with a sensitivity of 63% and a specificity of 83% using the cutoff value of 11.59 copies of CXCR3. Immunohistologic analysis of allograft biopsies showed exuberant expression of IP-10 and CXCR3 during acute rejection whereas both were absent in grafts with stable function.
Our investigation demonstrates that intragraft cellular events associated with acute rejection of human renal allografts can be noninvasively identified by measurements of mRNA for IP-10 and CXCR3 in urinary cells.</description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1111/j.1523-1755.2004.00663.x</identifier><identifier>PMID: 15149352</identifier><identifier>CODEN: KDYIA5</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Base Sequence ; Biological and medical sciences ; Chemokine CXCL10 ; chemokines ; Chemokines, CXC - genetics ; DNA - genetics ; Female ; Graft Rejection - diagnosis ; Graft Rejection - genetics ; Graft Rejection - immunology ; Humans ; Inflammation - diagnosis ; Inflammation - genetics ; Inflammation - immunology ; Kidney Transplantation - adverse effects ; Kidney Transplantation - immunology ; Kidney Transplantation - pathology ; Male ; Medical sciences ; Middle Aged ; mRNA ; Nephrology. Urinary tract diseases ; Receptors, Chemokine - genetics ; Receptors, CXCR3 ; rejection ; RNA, Messenger - genetics ; RNA, Messenger - urine ; ROC Curve</subject><ispartof>Kidney international, 2004-06, Vol.65 (6), p.2390-2397</ispartof><rights>2004 International Society of Nephrology</rights><rights>2004 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jun 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-7608de94314273f3eea66d6cb455496592a946cc045ba31ffa198c0c939816d83</citedby><cites>FETCH-LOGICAL-c477t-7608de94314273f3eea66d6cb455496592a946cc045ba31ffa198c0c939816d83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/210113627?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,64364,64366,64368,72218</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15835215$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15149352$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tatapudi, Ravi Raju</creatorcontrib><creatorcontrib>Muthukumar, Thangamani</creatorcontrib><creatorcontrib>Dadhania, Darshana</creatorcontrib><creatorcontrib>Ding, Ruchuang</creatorcontrib><creatorcontrib>Li, Baogui</creatorcontrib><creatorcontrib>Sharma, Vijay K.</creatorcontrib><creatorcontrib>Lozada-Pastorio, Elizabeth</creatorcontrib><creatorcontrib>Seetharamu, Nagashree</creatorcontrib><creatorcontrib>Hartono, Choli</creatorcontrib><creatorcontrib>Serur, David</creatorcontrib><creatorcontrib>Seshan, Surya V.</creatorcontrib><creatorcontrib>Kapur, Sandip</creatorcontrib><creatorcontrib>Hancock, Wayne W.</creatorcontrib><creatorcontrib>Suthanthiran, Manikkam</creatorcontrib><title>Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine</title><title>Kidney international</title><addtitle>Kidney Int</addtitle><description>Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine.
We explored the hypothesis that measurements of mRNA encoding interferon-inducible protein-10 (IP-10) or the chemokine receptor CXCR3 in urinary cells offer a noninvasive means of elucidating cellular traffic causing acute rejection of human renal allografts.
We obtained 63 urine specimens from 58 renal allograft recipients who underwent 63 allograft biopsies to resolve the basis for graft dysfunction, and 27 additional urine samples from 24 other patients with stable allograft function. Twenty-seven of the 63 biopsies were classified as acute rejection, 20 as other, and 16 as chronic allograft nephropathy. We measured the levels of transcripts for IP-10 and CXCR3, and a constitutively expressed gene 18S rRNA in the urine specimens and correlated transcript levels with renal allograft diagnosis.
mRNA levels of IP-10 (P < 0.0001) or CXCR3 (P < 0.0001) but not the levels of 18S rRNA (P = 0.56) predicted intragraft cellular traffic causing acute rejection. Receiver-operating characteristic curve analysis demonstrated that acute rejection can be predicted with a sensitivity of 100% and a specificity of 78% using the (log-transformed) cutoff value of 9.11 copies of IP-10, and with a sensitivity of 63% and a specificity of 83% using the cutoff value of 11.59 copies of CXCR3. Immunohistologic analysis of allograft biopsies showed exuberant expression of IP-10 and CXCR3 during acute rejection whereas both were absent in grafts with stable function.
Our investigation demonstrates that intragraft cellular events associated with acute rejection of human renal allografts can be noninvasively identified by measurements of mRNA for IP-10 and CXCR3 in urinary cells.</description><subject>Adult</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Chemokine CXCL10</subject><subject>chemokines</subject><subject>Chemokines, CXC - genetics</subject><subject>DNA - genetics</subject><subject>Female</subject><subject>Graft Rejection - diagnosis</subject><subject>Graft Rejection - genetics</subject><subject>Graft Rejection - immunology</subject><subject>Humans</subject><subject>Inflammation - diagnosis</subject><subject>Inflammation - genetics</subject><subject>Inflammation - immunology</subject><subject>Kidney Transplantation - adverse effects</subject><subject>Kidney Transplantation - immunology</subject><subject>Kidney Transplantation - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>mRNA</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Receptors, Chemokine - genetics</subject><subject>Receptors, CXCR3</subject><subject>rejection</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - urine</subject><subject>ROC Curve</subject><issn>0085-2538</issn><issn>1523-1755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkV-L1DAUxYMo7uzoV5Ag6Ftr0vxp87gO6i4sqywKvoVMeiMpbbIm7bD77U13BhVfzEsI93cON-cghCmpaTnvhpqKhlW0FaJuCOE1IVKy-v4J2vwePEUbQjpRNYJ1Z-g854GUt2LkOTqjgnLFRLNBw00MPhxM9gfAPcxgZx8Djg4nCGbEZhzjj2TcjH1wo5km8zjfP-AJTF4STBDmvPLT7c0FdjHhqy8VJdiEHu--725ZEeIl-QAv0DNnxgwvT_cWffv44evusrr-_Olqd3FdWd62c9VK0vWgOKO8aZljAEbKXto9F4IrKVRjFJfWEi72hlHnDFWdJVYx1VHZd2yL3h5971L8uUCe9eSzhXE0AeKSdUtXc7qCr_8Bh7ik8uusG0ooZbIssEXdEbIp5pzA6bvkJ5MeNCV6LUMPes1cr5nrtQz9WIa-L9JXJ_9lP0H_R3hKvwBvToDJ1owumWB9_ovrCkVF4d4fOSixHTwkna2HYKH3qRSm--j_v80vOxil9g</recordid><startdate>20040601</startdate><enddate>20040601</enddate><creator>Tatapudi, Ravi Raju</creator><creator>Muthukumar, Thangamani</creator><creator>Dadhania, Darshana</creator><creator>Ding, Ruchuang</creator><creator>Li, Baogui</creator><creator>Sharma, Vijay K.</creator><creator>Lozada-Pastorio, Elizabeth</creator><creator>Seetharamu, Nagashree</creator><creator>Hartono, Choli</creator><creator>Serur, David</creator><creator>Seshan, Surya V.</creator><creator>Kapur, Sandip</creator><creator>Hancock, Wayne W.</creator><creator>Suthanthiran, Manikkam</creator><general>Elsevier Inc</general><general>Nature Publishing</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><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>3V.</scope><scope>7QP</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>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20040601</creationdate><title>Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine</title><author>Tatapudi, Ravi Raju ; Muthukumar, Thangamani ; Dadhania, Darshana ; Ding, Ruchuang ; Li, Baogui ; Sharma, Vijay K. ; Lozada-Pastorio, Elizabeth ; Seetharamu, Nagashree ; Hartono, Choli ; Serur, David ; Seshan, Surya V. ; Kapur, Sandip ; Hancock, Wayne W. ; Suthanthiran, Manikkam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-7608de94314273f3eea66d6cb455496592a946cc045ba31ffa198c0c939816d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adult</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Chemokine CXCL10</topic><topic>chemokines</topic><topic>Chemokines, CXC - genetics</topic><topic>DNA - genetics</topic><topic>Female</topic><topic>Graft Rejection - diagnosis</topic><topic>Graft Rejection - genetics</topic><topic>Graft Rejection - immunology</topic><topic>Humans</topic><topic>Inflammation - diagnosis</topic><topic>Inflammation - genetics</topic><topic>Inflammation - immunology</topic><topic>Kidney Transplantation - adverse effects</topic><topic>Kidney Transplantation - immunology</topic><topic>Kidney Transplantation - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>mRNA</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Receptors, Chemokine - genetics</topic><topic>Receptors, CXCR3</topic><topic>rejection</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - urine</topic><topic>ROC Curve</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tatapudi, Ravi Raju</creatorcontrib><creatorcontrib>Muthukumar, Thangamani</creatorcontrib><creatorcontrib>Dadhania, Darshana</creatorcontrib><creatorcontrib>Ding, Ruchuang</creatorcontrib><creatorcontrib>Li, Baogui</creatorcontrib><creatorcontrib>Sharma, Vijay K.</creatorcontrib><creatorcontrib>Lozada-Pastorio, Elizabeth</creatorcontrib><creatorcontrib>Seetharamu, Nagashree</creatorcontrib><creatorcontrib>Hartono, Choli</creatorcontrib><creatorcontrib>Serur, David</creatorcontrib><creatorcontrib>Seshan, Surya V.</creatorcontrib><creatorcontrib>Kapur, Sandip</creatorcontrib><creatorcontrib>Hancock, Wayne W.</creatorcontrib><creatorcontrib>Suthanthiran, Manikkam</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</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</collection><collection>ProQuest One Community College</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>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><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Kidney international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tatapudi, Ravi Raju</au><au>Muthukumar, Thangamani</au><au>Dadhania, Darshana</au><au>Ding, Ruchuang</au><au>Li, Baogui</au><au>Sharma, Vijay K.</au><au>Lozada-Pastorio, Elizabeth</au><au>Seetharamu, Nagashree</au><au>Hartono, Choli</au><au>Serur, David</au><au>Seshan, Surya V.</au><au>Kapur, Sandip</au><au>Hancock, Wayne W.</au><au>Suthanthiran, Manikkam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine</atitle><jtitle>Kidney international</jtitle><addtitle>Kidney Int</addtitle><date>2004-06-01</date><risdate>2004</risdate><volume>65</volume><issue>6</issue><spage>2390</spage><epage>2397</epage><pages>2390-2397</pages><issn>0085-2538</issn><eissn>1523-1755</eissn><coden>KDYIA5</coden><abstract>Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine.
We explored the hypothesis that measurements of mRNA encoding interferon-inducible protein-10 (IP-10) or the chemokine receptor CXCR3 in urinary cells offer a noninvasive means of elucidating cellular traffic causing acute rejection of human renal allografts.
We obtained 63 urine specimens from 58 renal allograft recipients who underwent 63 allograft biopsies to resolve the basis for graft dysfunction, and 27 additional urine samples from 24 other patients with stable allograft function. Twenty-seven of the 63 biopsies were classified as acute rejection, 20 as other, and 16 as chronic allograft nephropathy. We measured the levels of transcripts for IP-10 and CXCR3, and a constitutively expressed gene 18S rRNA in the urine specimens and correlated transcript levels with renal allograft diagnosis.
mRNA levels of IP-10 (P < 0.0001) or CXCR3 (P < 0.0001) but not the levels of 18S rRNA (P = 0.56) predicted intragraft cellular traffic causing acute rejection. Receiver-operating characteristic curve analysis demonstrated that acute rejection can be predicted with a sensitivity of 100% and a specificity of 78% using the (log-transformed) cutoff value of 9.11 copies of IP-10, and with a sensitivity of 63% and a specificity of 83% using the cutoff value of 11.59 copies of CXCR3. Immunohistologic analysis of allograft biopsies showed exuberant expression of IP-10 and CXCR3 during acute rejection whereas both were absent in grafts with stable function.
Our investigation demonstrates that intragraft cellular events associated with acute rejection of human renal allografts can be noninvasively identified by measurements of mRNA for IP-10 and CXCR3 in urinary cells.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>15149352</pmid><doi>10.1111/j.1523-1755.2004.00663.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ProQuest Central UK/Ireland; Alma/SFX Local Collection |
| subjects | Adult Base Sequence Biological and medical sciences Chemokine CXCL10 chemokines Chemokines, CXC - genetics DNA - genetics Female Graft Rejection - diagnosis Graft Rejection - genetics Graft Rejection - immunology Humans Inflammation - diagnosis Inflammation - genetics Inflammation - immunology Kidney Transplantation - adverse effects Kidney Transplantation - immunology Kidney Transplantation - pathology Male Medical sciences Middle Aged mRNA Nephrology. Urinary tract diseases Receptors, Chemokine - genetics Receptors, CXCR3 rejection RNA, Messenger - genetics RNA, Messenger - urine ROC Curve |
| title | Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine |
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