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Molecular diagnostics identifies risks for graft dysfunction despite borderline histologic changes
- Source :
- Kidney international. 88(4)
- Publication Year :
- 2014
-
Abstract
- 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.
- Subjects :
- Adult
Genetic Markers
Graft Rejection
Male
Pathology
medicine.medical_specialty
Time Factors
Microarray
Biopsy
Fibrinogen
Kidney
Polymerase Chain Reaction
Risk Assessment
Immune system
Predictive Value of Tests
Risk Factors
medicine
Humans
Genetic Predisposition to Disease
Kidney transplantation
Subclinical infection
Aged
Oligonucleotide Array Sequence Analysis
Retrospective Studies
Microarray analysis techniques
business.industry
Gene Expression Profiling
Reproducibility of Results
Middle Aged
medicine.disease
Kidney Transplantation
Fibrinogen complex
Early Diagnosis
Phenotype
Treatment Outcome
Gene Expression Regulation
Molecular Diagnostic Techniques
Nephrology
Cohort
Asymptomatic Diseases
Female
sense organs
business
medicine.drug
Subjects
Details
- ISSN :
- 15231755
- Volume :
- 88
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Kidney international
- Accession number :
- edsair.doi.dedup.....6409a571d667dad3a9ecd843d84770c8