Histological analysis of biopsy at one year is proposed as a reliable tool for assessing renal allograft status, however, a non-invasive method for early prediction of graft outcome would be invaluable for clinical decision-making following transplant. In this study, gene expression microarrays and cell phenotype were performed on blood mononuclear cells at 3 months post-transplantation for 79 renal recipients and were investigated for prediction of graft histological lesion at one year. Four histological groups based on 1-year post-transplantation biopsy were defined: normal biopsy (n=45), signs of interstitial fibrosis and tubular atrophy (IFTA) (n=14), IFTA and inflammation (i-IFTA) (n=14) and alloimmune lesions (n=6). We found blood gene expression can be associated and furthermore predict graft alteration at one year post-transplantation. Indeed, 3-months blood signatures of IFTA, i-IFTA and alloimmune lesions compared to normal histology with biologically coherent patterns were highlighted. Furthermore, the combination of only 3 genes with the 3-months estimated glomerular filtration rate discriminates patients with 1-year normal biopsy with an area under a ROC curve of 0.76 after bootstrap resampling validation. This minimally invasive, early signature may improve our understanding of graft injury and facilitate early diagnostic and adjustment of therapy before graft injury.

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