Early prognosis of the development of renal chronic allograft rejection by gene expression profiling of human protocol biopsies

Transplantation. 2003 Apr 27;75(8):1323-30. doi: 10.1097/01.TP.0000068481.98801.10.


Background: Chronic allograft rejection (CR) is the major cause of failure of long-term graft survival and is so far irreversible. Early prognosis of CR by molecular markers before overt histologic manifestation would be a valuable aid for the optimization of treatment regimens and the design of clinical CR trials. Oligonucleotide microarray-based approaches have proven to be useful for the diagnosis and prognosis of a variety of diseases and were chosen for the unbiased identification of prognostic biomarkers.

Methods: Renal allograft biopsies were taken at month 6 posttransplantation (PT) from two groups who were, at that time, healthy recipients: one group developed CR at month-12 PT, the other group remained healthy. Gene expression profiles from the two groups at month-6 PT biopsies were analyzed to identify differentially expressed genes with prognostic value for CR development at month 12.

Results: A set of 10 genes was identified that showed differential expression profiles between the two patient groups and had a complete separation of the 15% to 85% quantile range for each individual gene. This set of genes was sufficient to allow the correct prediction of the occurrence or nonoccurrence of CR in 15 of 17 (88%) patients using cross-validation (occurrence for a patient was predicted on the basis of the other patients' data only). In addition, a correct prediction could be made that a recipient with a normal biopsy 12 months PT developed CR within the following 6 months.

Conclusions: Identified expression patterns seem to be highly prognostic of the development of renal CR.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adult
  • Biopsy
  • Chronic Disease
  • Female
  • Gene Expression Profiling*
  • Graft Rejection*
  • Humans
  • Kidney / pathology
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Prognosis
  • Reference Values
  • Time Factors
  • Transplantation, Homologous