Urinary Cell Gene Signature of Acute Rejection in Kidney Allografts

This is the authors' abstract. We don't add key points for this paper.

Introduction: A kidney allograft biopsy may display acute T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), or concurrent TCMR + ABMR (MR). Development of noninvasive biomarkers diagnostic of all three types of acute rejection is a useful addition to the diagnostic armamentarium. We determined whether the signature score in biopsy-matched urine specimens discriminates biopsies without rejection (NR, n=50) from biopsies displaying TCMR (n=47), ABMR (n=28) or MR (n=20). Results: Urinary cell three-gene signature discriminated TCMR, ABMR or MR biopsies from NR biopsies (P <0.0001, One-way ANOVA). Dunnett's multiple comparisons test yielded P<0.0001 for NR vs. TCMR; P <0.001 for NR vs. ABMR; and P <0.0001 for NR vs. MR. By bootstrap resampling, optimism-corrected area under the receiver operating characteristic curve (AUC) was 0.749 (bias-corrected 95% confidence interval [CI], 0.638 to 0.840) for NR vs. TCMR (P<0.0001); 0.780 (95% CI, 0.656 to 0.878) for NR vs. ABMR (P<0.0001); and 0.857 (95% CI, 0.727 to 0.947) for NR vs. MR (P<0.0001). All three rejection biopsy categories were distinguished from NR biopsies with similar accuracy (all AUC comparisons P>0.05). Conclusion: Urinary cell three-gene signature score may serve as a universal diagnostic signature of acute rejection due to TCMR, ABMR or MR in human kidney allografts with similar performance characteristics.