Detection of Subclinical Rejection in Pediatric Kidney Transplantation: Current and Future Practices
ABSTRACT Introduction The successes in the field of pediatric kidney transplantation over the past 60 years have been extraordinary. Year over year, there have been significant improvements in short‐term graft survival. However, improvements in longer‐term outcomes have been much less apparent. One...
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| Veröffentlicht in: | Pediatric transplantation 2024-09, Vol.28 (6), p.e14836-n/a |
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| creator | Ettenger, Robert B. Seifert, Michael E. Blydt‐Hansen, Tom Briscoe, David M. Holman, John Weng, Patricia L. Srivastava, Rachana Fleming, James Malekzadeh, Mohammed Pearl, Meghan |
| description | ABSTRACT
Introduction
The successes in the field of pediatric kidney transplantation over the past 60 years have been extraordinary. Year over year, there have been significant improvements in short‐term graft survival. However, improvements in longer‐term outcomes have been much less apparent. One important contributor has been the phenomenon of low‐level rejection in the absence of clinical manifestations—so‐called subclinical rejection (SCR).
Methods
Traditionally, rejection has been diagnosed by changes in clinical parameters, including but not limited to serum creatinine and proteinuria. This review examines the shortcomings of this approach, the effects of SCR on kidney allograft outcome, the benefits and drawbacks of surveillance biopsies to identify SCR, and new urine and blood biomarkers that define the presence or absence of SCR.
Results
Serum creatinine is an unreliable index of SCR. Surveillance biopsies are the method most utilized to detect SCR. However, these have significant drawbacks. New biomarkers show promise. These biomarkers include blood gene expression profiles and donor derived‐cell free DNA; urine gene expression profiles; urinary cytokines, chemokines, and metabolomics; and other promising blood and urine tests.
Conclusion
Specific emphasis is placed on studies carried out in pediatric kidney transplant recipients.
Trial Registration: ClinicalTrials.gov: NCT03719339 |
| doi_str_mv | 10.1111/petr.14836 |
| format | Article |
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Introduction
The successes in the field of pediatric kidney transplantation over the past 60 years have been extraordinary. Year over year, there have been significant improvements in short‐term graft survival. However, improvements in longer‐term outcomes have been much less apparent. One important contributor has been the phenomenon of low‐level rejection in the absence of clinical manifestations—so‐called subclinical rejection (SCR).
Methods
Traditionally, rejection has been diagnosed by changes in clinical parameters, including but not limited to serum creatinine and proteinuria. This review examines the shortcomings of this approach, the effects of SCR on kidney allograft outcome, the benefits and drawbacks of surveillance biopsies to identify SCR, and new urine and blood biomarkers that define the presence or absence of SCR.
Results
Serum creatinine is an unreliable index of SCR. Surveillance biopsies are the method most utilized to detect SCR. However, these have significant drawbacks. New biomarkers show promise. These biomarkers include blood gene expression profiles and donor derived‐cell free DNA; urine gene expression profiles; urinary cytokines, chemokines, and metabolomics; and other promising blood and urine tests.
Conclusion
Specific emphasis is placed on studies carried out in pediatric kidney transplant recipients.
Trial Registration: ClinicalTrials.gov: NCT03719339</description><identifier>ISSN: 1397-3142</identifier><identifier>ISSN: 1399-3046</identifier><identifier>EISSN: 1399-3046</identifier><identifier>DOI: 10.1111/petr.14836</identifier><identifier>PMID: 39147695</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Biomarkers ; Biomarkers - blood ; Biomarkers - urine ; Biopsy ; Blood ; Chemokines ; Child ; Creatinine ; Creatinine - blood ; Gene expression ; Graft rejection ; Graft Rejection - blood ; Graft Rejection - diagnosis ; Graft Survival ; Humans ; Kidney Transplantation ; Kidney transplants ; Metabolomics ; Observational Studies as Topic ; pediatric kidney transplantation ; Pediatrics ; Proteinuria ; subclinical rejection ; Surveillance ; Urine</subject><ispartof>Pediatric transplantation, 2024-09, Vol.28 (6), p.e14836-n/a</ispartof><rights>2024 The Author(s). published by Wiley Periodicals LLC.</rights><rights>2024 The Author(s). Pediatric Transplantation published by Wiley Periodicals LLC.</rights><rights>2024. This article is published under http://creativecommons.org/licenses/by-nc-nd/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><cites>FETCH-LOGICAL-c2826-60bf7c4e162ec78080a0796c5d6c6e4a1efceac68e21e862aa4be1d86f71ff1e3</cites><orcidid>0000-0002-8864-0197 ; 0000-0002-6588-0315 ; 0000-0003-4135-5417 ; 0000-0003-2020-2729 ; 0000-0002-0557-6178 ; 0000-0001-6459-0925 ; 0000-0002-9973-7349 ; 0000-0001-9686-3107</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fpetr.14836$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fpetr.14836$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39147695$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ettenger, Robert B.</creatorcontrib><creatorcontrib>Seifert, Michael E.</creatorcontrib><creatorcontrib>Blydt‐Hansen, Tom</creatorcontrib><creatorcontrib>Briscoe, David M.</creatorcontrib><creatorcontrib>Holman, John</creatorcontrib><creatorcontrib>Weng, Patricia L.</creatorcontrib><creatorcontrib>Srivastava, Rachana</creatorcontrib><creatorcontrib>Fleming, James</creatorcontrib><creatorcontrib>Malekzadeh, Mohammed</creatorcontrib><creatorcontrib>Pearl, Meghan</creatorcontrib><title>Detection of Subclinical Rejection in Pediatric Kidney Transplantation: Current and Future Practices</title><title>Pediatric transplantation</title><addtitle>Pediatr Transplant</addtitle><description>ABSTRACT
Introduction
The successes in the field of pediatric kidney transplantation over the past 60 years have been extraordinary. Year over year, there have been significant improvements in short‐term graft survival. However, improvements in longer‐term outcomes have been much less apparent. One important contributor has been the phenomenon of low‐level rejection in the absence of clinical manifestations—so‐called subclinical rejection (SCR).
Methods
Traditionally, rejection has been diagnosed by changes in clinical parameters, including but not limited to serum creatinine and proteinuria. This review examines the shortcomings of this approach, the effects of SCR on kidney allograft outcome, the benefits and drawbacks of surveillance biopsies to identify SCR, and new urine and blood biomarkers that define the presence or absence of SCR.
Results
Serum creatinine is an unreliable index of SCR. Surveillance biopsies are the method most utilized to detect SCR. However, these have significant drawbacks. New biomarkers show promise. These biomarkers include blood gene expression profiles and donor derived‐cell free DNA; urine gene expression profiles; urinary cytokines, chemokines, and metabolomics; and other promising blood and urine tests.
Conclusion
Specific emphasis is placed on studies carried out in pediatric kidney transplant recipients.
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Seifert, Michael E. ; Blydt‐Hansen, Tom ; Briscoe, David M. ; Holman, John ; Weng, Patricia L. ; Srivastava, Rachana ; Fleming, James ; Malekzadeh, Mohammed ; Pearl, Meghan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2826-60bf7c4e162ec78080a0796c5d6c6e4a1efceac68e21e862aa4be1d86f71ff1e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Biomarkers - urine</topic><topic>Biopsy</topic><topic>Blood</topic><topic>Chemokines</topic><topic>Child</topic><topic>Creatinine</topic><topic>Creatinine - blood</topic><topic>Gene expression</topic><topic>Graft rejection</topic><topic>Graft Rejection - blood</topic><topic>Graft Rejection - diagnosis</topic><topic>Graft Survival</topic><topic>Humans</topic><topic>Kidney Transplantation</topic><topic>Kidney transplants</topic><topic>Metabolomics</topic><topic>Observational Studies as Topic</topic><topic>pediatric kidney transplantation</topic><topic>Pediatrics</topic><topic>Proteinuria</topic><topic>subclinical rejection</topic><topic>Surveillance</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ettenger, Robert B.</creatorcontrib><creatorcontrib>Seifert, Michael E.</creatorcontrib><creatorcontrib>Blydt‐Hansen, Tom</creatorcontrib><creatorcontrib>Briscoe, David M.</creatorcontrib><creatorcontrib>Holman, John</creatorcontrib><creatorcontrib>Weng, Patricia L.</creatorcontrib><creatorcontrib>Srivastava, Rachana</creatorcontrib><creatorcontrib>Fleming, James</creatorcontrib><creatorcontrib>Malekzadeh, Mohammed</creatorcontrib><creatorcontrib>Pearl, Meghan</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Pediatric transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ettenger, Robert B.</au><au>Seifert, Michael E.</au><au>Blydt‐Hansen, Tom</au><au>Briscoe, David M.</au><au>Holman, John</au><au>Weng, Patricia L.</au><au>Srivastava, Rachana</au><au>Fleming, James</au><au>Malekzadeh, Mohammed</au><au>Pearl, Meghan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Detection of Subclinical Rejection in Pediatric Kidney Transplantation: Current and Future Practices</atitle><jtitle>Pediatric transplantation</jtitle><addtitle>Pediatr Transplant</addtitle><date>2024-09</date><risdate>2024</risdate><volume>28</volume><issue>6</issue><spage>e14836</spage><epage>n/a</epage><pages>e14836-n/a</pages><issn>1397-3142</issn><issn>1399-3046</issn><eissn>1399-3046</eissn><abstract>ABSTRACT
Introduction
The successes in the field of pediatric kidney transplantation over the past 60 years have been extraordinary. Year over year, there have been significant improvements in short‐term graft survival. However, improvements in longer‐term outcomes have been much less apparent. One important contributor has been the phenomenon of low‐level rejection in the absence of clinical manifestations—so‐called subclinical rejection (SCR).
Methods
Traditionally, rejection has been diagnosed by changes in clinical parameters, including but not limited to serum creatinine and proteinuria. This review examines the shortcomings of this approach, the effects of SCR on kidney allograft outcome, the benefits and drawbacks of surveillance biopsies to identify SCR, and new urine and blood biomarkers that define the presence or absence of SCR.
Results
Serum creatinine is an unreliable index of SCR. Surveillance biopsies are the method most utilized to detect SCR. However, these have significant drawbacks. New biomarkers show promise. These biomarkers include blood gene expression profiles and donor derived‐cell free DNA; urine gene expression profiles; urinary cytokines, chemokines, and metabolomics; and other promising blood and urine tests.
Conclusion
Specific emphasis is placed on studies carried out in pediatric kidney transplant recipients.
Trial Registration: ClinicalTrials.gov: NCT03719339</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>39147695</pmid><doi>10.1111/petr.14836</doi><tpages>19</tpages><orcidid>https://orcid.org/0000-0002-8864-0197</orcidid><orcidid>https://orcid.org/0000-0002-6588-0315</orcidid><orcidid>https://orcid.org/0000-0003-4135-5417</orcidid><orcidid>https://orcid.org/0000-0003-2020-2729</orcidid><orcidid>https://orcid.org/0000-0002-0557-6178</orcidid><orcidid>https://orcid.org/0000-0001-6459-0925</orcidid><orcidid>https://orcid.org/0000-0002-9973-7349</orcidid><orcidid>https://orcid.org/0000-0001-9686-3107</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Biomarkers Biomarkers - blood Biomarkers - urine Biopsy Blood Chemokines Child Creatinine Creatinine - blood Gene expression Graft rejection Graft Rejection - blood Graft Rejection - diagnosis Graft Survival Humans Kidney Transplantation Kidney transplants Metabolomics Observational Studies as Topic pediatric kidney transplantation Pediatrics Proteinuria subclinical rejection Surveillance Urine |
| title | Detection of Subclinical Rejection in Pediatric Kidney Transplantation: Current and Future Practices |
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