Molecular diagnostics identifies risks for graft dysfunction despite borderline histologic changes

Kidney Int. 2015 Oct;88(4):785-95. doi: 10.1038/ki.2015.211. Epub 2015 Jul 15.


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.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Asymptomatic Diseases
  • Biopsy
  • Early Diagnosis
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Markers*
  • Genetic Predisposition to Disease
  • Graft Rejection / genetics*
  • Graft Rejection / pathology*
  • Graft Rejection / physiopathology
  • Humans
  • Kidney / pathology*
  • Kidney / physiopathology
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Molecular Diagnostic Techniques*
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Polymerase Chain Reaction
  • Predictive Value of Tests
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome


  • Genetic Markers