Association of Noninvasive Rejection Biomarkers with 10-Year Kidney Allograft Survival.

KEY POINTS: There is an independent association between two independent noninvasive biomarkers and all-cause graft loss. Time-varying analysis demonstrated that the independent noninvasive biomarkers can provide more information than either one alone.

BACKGROUND

The primary objective of this analysis was to assess the association between noninvasive biomarker results within the first 2 years postkidney transplant and 10-year all-cause graft loss (ACGL).

METHODS

Clinical Trials in Organ Transplantation 08 (CTOT-08) study was linked with the Scientific Registry of Transplant Recipients to assess 10-year ACGL. Cox regression was used to determine the association between gene expression profile (GEP) and donor-derived cell-free DNA (dd-cfDNA) results and ACGL. A Cox regression with time-varying covariates was used to test associations with ACGL with simultaneous and repeated biomarker results.

RESULTS

The final landmarked Cox model included clinical acute rejection (adjusted hazard ratio [aHR], 2.58 [1.30 to 5.13] for one rejection; aHR, 3.41 [1.07 to 10.85] for two rejections), diabetes (aHR, 1.71 [0.99 to 2.96]), recipient age (aHR, 1.02 [1.00 to 1.04]), the highest quartile of positive GEP (aHR, 2.44 [1.45 to 4.10]), and the highest quartile of positive dd-cfDNA (aHR, 2.91 [1.77 to 4.78]). In the time-varying model, having both biomarkers positive at the same time carried the greatest association with ACGL (aHR, 4.29 [2.10 to 8.76]).

CONCLUSIONS

In this multicenter, prospective analysis of GEP and dd-cfDNA on patient and graft outcomes, an independent association with long-term ACGL was demonstrated. Furthermore, a time-varying analysis demonstrated that two biomarkers with independent methodologies tested at the same time can provide more information than either one alone.

CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrials.gov, NCT01531257 .