دورية أكاديمية
Effects of anti-adhesive therapy on kidney biomarkers of ischemia reperfusion injury in human deceased donor kidney allografts.
| العنوان: | Effects of anti-adhesive therapy on kidney biomarkers of ischemia reperfusion injury in human deceased donor kidney allografts. |
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| المؤلفون: | Cheadle C; Lowe Family Genomics Core, Johns Hopkins University, Baltimore, MD, USA., Watkins T, Ehrlich E, Barnes K, Gaber AO, Hemmerich S, Rabb H |
| المصدر: | Clinical transplantation [Clin Transplant] 2011 Sep-Oct; Vol. 25 (5), pp. 766-75. Date of Electronic Publication: 2010 Nov 28. |
| نوع المنشور: | Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Munksgaard Country of Publication: Denmark NLM ID: 8710240 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1399-0012 (Electronic) Linking ISSN: 09020063 NLM ISO Abbreviation: Clin Transplant Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Copenhagen : Munksgaard, |
| مواضيع طبية MeSH: | Tissue Donors*, Biomarkers/*analysis , Cytokines/*genetics , Kidney/*physiopathology , Membrane Glycoproteins/*metabolism , Recombinant Fusion Proteins/*therapeutic use , Reperfusion Injury/*diagnosis , Reperfusion Injury/*prevention & control, Adult ; Aged ; Cadaver ; Cohort Studies ; Double-Blind Method ; Female ; Follow-Up Studies ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; P-Selectin/antagonists & inhibitors ; Prognosis ; Real-Time Polymerase Chain Reaction ; Reperfusion ; Reperfusion Injury/genetics ; Transplantation, Homologous |
| مستخلص: | Introduction: Molecular biomarkers validated previously in animal models are increasingly being studied in conjunction with traditional clinical endpoints in therapeutic trials. Patient and Methods: We hypothesized that human kidneys would exhibit a brisk, gene-specific inflammatory response during ischemia reperfusion injury (IRI), which would be modified by anti-adhesive therapy. Forty deceased-donor kidneys were biopsied prior to implantation and ∼1 h after reperfusion during an intervention trial with the selectin antagonist YSPSL (recombinant P-selectin glycoprotein ligand Ig). Ten inflammatory genes were measured by RT-PCR and normalized to three housekeeping genes. Results: Pre-implantation kidney biopsies were already significantly inflamed relative to healthy tissue, with transcripts encoding IL-6, IL-8, and CD25 > 10-fold elevated. After reperfusion, IL-6 and IL-8 increased additional 60- and 120-fold (p < 0.05), while already elevated CD25-levels remained stable. Furthermore, transcripts encoding MCP-1, E-selectin, and TNFα were also induced significantly upon reperfusion (p < 0.0005). Systemic treatment of the recipient with YSPSL pre-reperfusion, with or without pre-implantation YSPSL flush of the donor organ, attenuated the post-reperfusion increase in MCP-1 and TGFβ (p < 0.05), E-selectin and hemoxygenase 1 transcripts (p < 0.1). Conclusions: Our data in humans demonstrate a robust increase in inflammatory gene transcript levels during kidney transplantation IRI and reduction thereof by inhibition of leukocyte adhesion. (© 2010 John Wiley & Sons A/S.) |
| سلسلة جزيئية: | ClinicalTrials.gov NCT00298168 |
| المشرفين على المادة: | 0 (Biomarkers) 0 (Cytokines) 0 (Membrane Glycoproteins) 0 (P-Selectin) 0 (P-selectin ligand protein) 0 (Recombinant Fusion Proteins) |
| تواريخ الأحداث: | Date Created: 20101201 Date Completed: 20120214 Latest Revision: 20151119 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1111/j.1399-0012.2010.01365.x |
| PMID: | 21114535 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1399-0012 |
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| DOI: | 10.1111/j.1399-0012.2010.01365.x |