Interstitial fibrosis and tubular atrophy (IFTA) with inflammation (IFTA-I) is strongly correlated with kidney allograft failure. Diagnosis of IFTA-I accurately and early is critical to prevent graft failure and improve graft survival. In the current study, through analyzing the renal allograft biopsy in patients with stable function after kidney transplantation (STA), IFTA and IFTA-I group with semi-supervised principal components methods, we found that CD2, IL7R, CCL5 based signature could not only distinguish STA and IFTA-I well, but predict IFTA-I with a high degree of accuracy with an area under the curve (AUC) of 0.91 ( = 0.00023). Additionally, IRF8 demonstrated significant differences among STA, IFTA and IFTA-I groups, suggesting that IRF8 had the capacity to discriminate the different classifications of graft biopsies well. Also, with Kaplan-Meier and log-rank methods, we found that IRF8 could serve as the prognostic marker for renal graft failure in those biopsies without rejection (AUC = 0.75) and the recipients expressing high had a higher risk for renal graft loss ( < 0.0001). This research may provide new targets for therapeutic prevention and intervention for post-transplantation IFTA with or with inflammation.