Schütz, Ekkehard

[["dc.bibliographiccitation.artnumber","1031894"],["dc.bibliographiccitation.journal","Frontiers in Genetics"],["dc.bibliographiccitation.volume","13"],["dc.contributor.affiliation","Oellerich, Michael; \r\n1\r\nDepartment of Clinical Pharmacology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Budde, Klemens; \r\n2\r\nDepartment of Nephrology and Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany"],["dc.contributor.affiliation","Osmanodja, Bilgin; \r\n2\r\nDepartment of Nephrology and Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany"],["dc.contributor.affiliation","Bornemann-Kolatzki, Kirsten; \r\n3\r\nChronix Biomedical GmbH, Göttingen, Germany"],["dc.contributor.affiliation","Beck, Julia; \r\n3\r\nChronix Biomedical GmbH, Göttingen, Germany"],["dc.contributor.affiliation","Schütz, Ekkehard; \r\n3\r\nChronix Biomedical GmbH, Göttingen, Germany"],["dc.contributor.affiliation","Walson, Philip D.; \r\n1\r\nDepartment of Clinical Pharmacology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Budde, Klemens"],["dc.contributor.author","Osmanodja, Bilgin"],["dc.contributor.author","Bornemann-Kolatzki, Kirsten"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Schütz, Ekkehard"],["dc.contributor.author","Walson, Philip D."],["dc.date.accessioned","2022-12-01T08:31:30Z"],["dc.date.available","2022-12-01T08:31:30Z"],["dc.date.issued","2022"],["dc.date.updated","2022-11-11T13:12:26Z"],["dc.description.abstract","There is a need to improve personalized immunosuppression in organ transplantation to reduce premature graft loss. Biomarkers are needed to better detect rejection, asymptomatic graft injury, and under-immunosuppression. Assessment of minimal necessary exposure to guide tapering and prevent immune activation is also important. There is robust clinical evidence from a large number of published studies supporting the role of dd-cfDNA for monitoring graft integrity and detection or exclusion of rejection. Dd-cfDNA indicates graft cell death without being rejection specific. It can be determined in plasma through droplet digital PCR using preselected SNPs or next generation sequencing. Changes in recipient cfDNA (e.g., by infection) can affect the results of dd-cfDNA fractional determination. This limitation can be overcome using absolute dd-cfDNA quantification. The combination of fractional and absolute determination including total cfDNA is recommended for meaningful interpretation of the results. The value proposition for the patient includes earlier transplant injury detection and intervention, less full blown rejection risk, an alternative to invasive biopsies, and personalized immunosuppression with potential for improved long-term outcome. Transplant physicians benefit from better immunosuppressive guidance and having an alternative when biopsies are refused or contraindicated. Further advantages are improved biopsy interpretation, less trial and error changes in immunosuppression, and less time dealing with complications. The laboratory medicine specialist can provide more effective services. Hospital management and insurance companies could benefit from more cost-effective surveillance of transplant recipients. Potential cost savings would result from fewer biopsies as a result of the tests’ high negative predictive value, fewer re-transplantations, and less organ failure with return to dialysis. A pathway to implementation and metrics is suggested to measure the effectiveness of dd-cfDNA testing."],["dc.identifier.doi","10.3389/fgene.2022.1031894"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/118187"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.eissn","1664-8021"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Donor-derived cell-free DNA as a diagnostic tool in transplantation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1002286"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLoS Medicine"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Schütz, Ekkehard"],["dc.contributor.author","Fischer, Anna"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Harden, Markus"],["dc.contributor.author","Koch, Martina"],["dc.contributor.author","Wuensch, Tilo"],["dc.contributor.author","Stockmann, Martin"],["dc.contributor.author","Nashan, Bjoern"],["dc.contributor.author","Kollmar, Otto"],["dc.contributor.author","Matthaei, Johannes"],["dc.contributor.author","Kanzow, Philipp"],["dc.contributor.author","Walson, Philip D."],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Oellerich, Michael"],["dc.date.accessioned","2018-11-07T10:25:24Z"],["dc.date.accessioned","2020-05-22T07:30:58Z"],["dc.date.available","2018-11-07T10:25:24Z"],["dc.date.available","2020-05-22T07:30:58Z"],["dc.date.issued","2017"],["dc.description.abstract","Background Graft-derived cell-free DNA (GcfDNA), which is released into the blood stream by necrotic and apoptotic cells, is a promising noninvasive organ integrity biomarker. In liver transplantation (LTx), neither conventional liver function tests (LTFs) nor immunosuppressive drug monitoring are very effective for rejection monitoring. We therefore hypothesized that the quantitative measurement of donor-derived cell-free DNA (cfDNA) would have independent value for the assessment of graft integrity, including damage from acute rejection. Methods and findings Traditional LFTs were performed and plasma GcfDNA was monitored in 115 adults post-LTx at three German transplant centers as part of a prospective, observational, multicenter cohort trial. GcfDNA percentage (graft cfDNA/total cfDNA) was measured using droplet digital PCR (ddPCR), based on a limited number of predefined single nucleotide polymorphisms, enabling same-day turn-around. The same method was used to quantify blood microchimerism. GcfDNA was increased >50% on day 1 post-LTx, presumably from ischemia/reperfusion damage, but rapidly declined in patients without graft injury within 7 to 10 d to a median <10%, where it remained for the 1-y observation period. Of 115 patients, 107 provided samples that met preestablished criteria. In 31 samples taken from 17 patients during biopsy-proven acute rejection episodes, the percentage of GcfDNA was elevated substantially (median 29.6%, 95% CI 23.6%-41.0%) compared with that in 282 samples from 88 patients during stable periods (median 3.3%, 95% CI 2.9%-3.7%; p < 0.001). Only slightly higher values (median 5.9%, 95% CI 4.4%-10.3%) were found in 68 samples from 17 hepatitis C virus (HCV)-positive, rejection-free patients. LFTs had low overall correlations (r = 0.28-0.62) with GcfDNA and showed greater overlap between patient subgroups, especially between acute rejection and HCV+ patients. Multivariable logistic regression modeling demonstrated that GcfDNA provided additional LFT-independent information on graft integrity. Diagnostic sensitivity and specificity were 90.3% (95% CI 74.2%-98.0%) and 92.9% (95% CI 89.3%-95.6%), respectively, for GcfDNA at a threshold value of 10%. The area under the receiver operator characteristic curve was higher for GcfDNA (97.1%, 95% CI 93.4%-100%) than for same-day conventional LFTs (AST: 95.7%; ALT: 95.2%; gamma-GT: 94.5%; bilirubin: 82.6%). An evaluation of microchimerism revealed that the maximum donor DNA in circulating white blood cells was only 0.068%. GcfDNA percentage can be influenced by major changes in host cfDNA (e.g., due to leukopenia or leukocytosis). One limitation of our study is that exact time-matched GcfDNA and LFT samples were not available for all patient visits. Conclusions In this study, determination of GcfDNA in plasma by ddPCR allowed for earlier and more sensitive discrimination of acute rejection in LTx patients as compared with conventional LFTs. Potential blood microchimerism was quantitatively low and had no significant influence on GcfDNA value. Further research, which should ideally include protocol biopsies, will be needed to establish the practical value of GcfDNA measurements in the management of LTx patients."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1371/journal.pmed.1002286"],["dc.identifier.isi","000400768500015"],["dc.identifier.pmid","28441386"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14418"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42852"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/65693"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1549-1676"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Graft-derived cell-free DNA, a noninvasive early rejection and graft damage marker in liver transplantation: A prospective, observational, multicenter cohort study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]