*Purpose: The CTOT08 trial showed that either histological subAR or positive gene expression profile (GEP) in the blood associated with histological subAR correlated with a composite clinical endpoint (CCE) of adverse graft outcomes by 2 yrs post-Tx. Despite a trend, neither subAR nor +GEP was significantly associated with worse eGFR, one of the 3 components of the CCE. We hypothesized that longer follow-up would unmask such an association.

*Methods: Graft survival and eGFR (CKD-EPI) at last follow up were collected on available CTOT08 subjects. Subjects were divided into 3 groups based on serial paired (histology or GEP) samples: 1) no subAR or -GEP only, 2) mixed (subAR & no subAR) or (+ & – GEP), and 3) subAR or + GEP only. Cox proportional hazard model was used for analyzing graft survival, and Kruskal-Wallis rank sum test to detect differences in eGFR among groups.

*Results: Data were available from 3/5 sites with 216 (85%) of 253 subjects included in CTOT08 analyses. 23/216 (11%) grafts failed at a mean follow-up of 5.2 years (1898 days: range 74-2716) post-Tx with no difference in time to graft failure between groups by either histology or GEP (HR 1.29 group 3 vs group 1; 95% CI (0.42, 3.9); p-value 0.659). In contrast, we observed a statistically significant difference in mean eGFR at last follow up between the 3 groups whether classified by biopsy (p=0.026) or GEP (p=0.033) (Table).

*Conclusions: At a mean follow-up of 5.2 years post-Tx, histological subAR in the first 2 years correlates with similar rates of graft failure but statistically lower and clinically meaningful differences in eGFR compared to subjects without subAR. These data show an unmasking of statistical significance with longer follow-up signaled by an earlier trend in patients with either clinical or molecular evidence of subAR. These data demonstrate further clinical validity of both the clinical and molecular phenotype of subAR vs no subAR.

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