Molecular diagnostics identifies risks for graft dysfunction despite borderline histologic changes
Language English Country United States Media print-electronic
Document type Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't, Validation Study
PubMed
26176825
DOI
10.1038/ki.2015.211
PII: S2157-1716(15)32267-X
Knihovny.cz E-resources
- MeSH
- Asymptomatic Diseases MeSH
- Biopsy MeSH
- Early Diagnosis MeSH
- Time Factors MeSH
- Molecular Diagnostic Techniques * MeSH
- Adult MeSH
- Phenotype MeSH
- Genetic Predisposition to Disease MeSH
- Genetic Markers * MeSH
- Risk Assessment MeSH
- Kidney pathology physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Polymerase Chain Reaction MeSH
- Predictive Value of Tests MeSH
- Gene Expression Regulation MeSH
- Graft Rejection genetics pathology physiopathology MeSH
- Reproducibility of Results MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Oligonucleotide Array Sequence Analysis MeSH
- Aged MeSH
- Gene Expression Profiling MeSH
- Kidney Transplantation adverse effects MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Observational Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Validation Study MeSH
- Names of Substances
- Genetic Markers * MeSH
The significance of borderline changes in kidney allograft biopsies is widely debated. To help resolve this, we studied differences in intrarenal gene expression patterns between early clinical and 3-month protocol biopsies, all of which had borderline histologic changes. The gene expression profiles in training set of patients by microarray analysis and data were validated in a larger cohort using RT-qPCR. There was greater expression of immunity- and inflammation-related genes in the early clinical biopsies compared to the 3-month protocol biopsies with borderline changes. In early clinically manifested borderline changes, graft deterioration within 24 months due to chronic rejection was associated with increased activation of immune, defense, and inflammatory processes. Regression modeling identified higher donor age and expression of macrophage receptor CLEC5A as risk factors for progression. In the 3-month protocol biopsies with borderline changes, graft dysfunction was associated with increased expression of fibrinogen complex transcripts. The discrimination power of fibrinogen was confirmed by cross-validation on two independent cohorts. Thus, our study highlights variations in gene expression between clinical and subclinical borderline changes despite similar histological findings. The data also support a recommendation for frequent patient monitoring, especially in those with borderline changes who received grafts from older donors.
Biomedical Centre Faculty of Medicine in Plzen Charles University Prague Plzen Czech Republic
Department of Immunogenetics Institute for Clinical and Experimental Medicine Prague Czech Republic
Department of Nephrology and Dialysis Medical University Vienna Vienna Austria
Department of Nephrology Hannover Medical School Hannover Germany
Department of Nephrology Institute for Clinical and Experimental Medicine Prague Czech Republic
Department of Urology Thomayer's Hospital Prague Czech Republic
Institute of Hematology and Blood Transfusion Prague Czech Republic
Transplant Laboratory Institute for Clinical and Experimental Medicine Prague Czech Republic
See more in PubMed
Transpl Int. 2009 Mar;22(3):293-302 PubMed
Am J Transplant. 2014 Feb;14(2):272-83 PubMed
J Exp Med. 2010 Mar 15;207(3):579-89 PubMed
J Am Soc Nephrol. 2006 Sep;17(9):2622-32 PubMed
Kidney Int. 1997 Jan;51(1):310-6 PubMed
Nature. 2008 May 29;453(7195):672-6 PubMed
Kidney Int. 2011 Nov;80(10):1035-44 PubMed
Transplantation. 2010 Mar 15;89(5):537-47 PubMed
J Clin Invest. 1950 May;29(5):496-507 PubMed
Transplant Proc. 2008 Sep;40(7):2303-6 PubMed
J Am Soc Nephrol. 2012 May;23(5):948-58 PubMed
N Engl J Med. 2003 Jul 10;349(2):125-38 PubMed
Transplantation. 2002 Jun 27;73(12):1965-8 PubMed
Transplant Proc. 1997 Feb-Mar;29(1-2):112 PubMed
J Leukoc Biol. 2009 Mar;85(3):508-17 PubMed
Eur J Immunol. 2003 Sep;33(9):2630-9 PubMed
Biochem Biophys Res Commun. 1998 Mar 6;244(1):268-74 PubMed
Genomics. 1997 May 1;41(3):471-6 PubMed
Am J Transplant. 2013 Mar;13(3):645-55 PubMed
Lancet. 1994 Jan 22;343(8891):209-11 PubMed
Am J Transplant. 2012 Jan;12(1):11-2 PubMed
Ann Diagn Pathol. 2013 Feb;17(1):75-9 PubMed
Am J Transplant. 2012 Jan;12(1):38-42 PubMed
Am J Transplant. 2004 Sep;4(9):1475-89 PubMed
Am J Kidney Dis. 1996 Oct;28(4):585-8 PubMed
Transplantation. 2013 Jan 15;95(1):148-54 PubMed
Am J Transplant. 2013 Sep;13(9):2334-41 PubMed
J Clin Invest. 2010 Jun;120(6):1862-72 PubMed
Transplant Proc. 2009 Apr;41(3):794-6 PubMed
Kidney Int. 2011 Dec;80(12):1364-76 PubMed
J Am Soc Nephrol. 1999 Aug;10(8):1806-14 PubMed
Am J Transplant. 2008 Apr;8(4):753-60 PubMed
Am J Transplant. 2005 May;5(5):1130-6 PubMed
Transplantation. 1994 Mar 27;57(6):871-6 PubMed
Transplantation. 1995 Feb 27;59(4):511-4 PubMed
Am J Transplant. 2012 Jan;12(1):191-201 PubMed
Exp Mol Pathol. 2007 Oct;83(2):188-97 PubMed
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