Clinical Value of Peripheral Blood Gene Expression Profile and dd-cfDNA for Identifying Persistent Rejection.

Area of Science:

• Nephrology
• Transplant Immunology
• Biomarker Discovery

Background:

• Persistent rejection is a significant obstacle to long-term kidney transplant success.
• A noninvasive method to detect persistent rejection is needed to guide clinical management.

Purpose of the Study:

• To evaluate the utility of peripheral blood gene expression profile (GEP) and donor-derived cell-free DNA (dd-cfDNA) in identifying persistent kidney allograft rejection.
• To assess the performance of these biomarkers in clinically stable patients.

Main Methods:

• Post-hoc analysis of a multicenter observational study.
• Included subjects with biopsy-proven acute rejection and a repeat biopsy within 9 months.
• Analyzed biopsy-paired peripheral blood samples for GEP and dd-cfDNA.

Main Results:

• Persistent rejection was found in 61% of subjects undergoing repeat biopsy.
• GEP showed 59% sensitivity and 76% specificity; dd-cfDNA showed 62% sensitivity and 86% specificity.
• In clinically stable patients with repeat biopsies within 90 days, both biomarkers achieved 100% specificity and PPV, with GEP indicating TCMR and dd-cfDNA indicating AMR.

Conclusions:

• Both GEP and dd-cfDNA show promise in identifying clinically stable kidney transplant recipients with persistent rejection who may require biopsy.
• These biomarkers identify different types of rejection, suggesting complementary roles in patient management.