Cell-Free DNA and Active Rejection in Kidney Allografts.

Area of Science:

• Nephrology
• Transplant Immunology
• Molecular Diagnostics

Background:

• Kidney transplant rejection diagnosis relies on invasive histologic analysis of biopsy specimens.
• Donor-derived cell-free DNA (dd-cfDNA) presents a promising noninvasive biomarker for allograft injury.
• Current methods for monitoring transplant status are limited in frequency and safety.

Purpose of the Study:

• To evaluate the utility of plasma dd-cfDNA levels in detecting and quantifying kidney allograft rejection.
• To correlate dd-cfDNA levels with histologic findings in kidney transplant recipients.
• To assess the potential of dd-cfDNA as a safer, more frequent alternative to biopsies.

Main Methods:

• Prospective collection of blood samples from 102 kidney transplant recipients at scheduled intervals and during biopsies.
• Measurement of plasma dd-cfDNA levels.
• Correlation of dd-cfDNA levels with allograft rejection status determined by histologic analysis of 107 biopsy specimens.

Main Results:

• dd-cfDNA levels significantly discriminated between rejection and control groups (AUC=0.74, P<0.001).
• A dd-cfDNA cutoff of 1.0% showed 61% positive and 84% negative predictive values for active rejection.
• dd-cfDNA demonstrated high accuracy in identifying antibody-mediated rejection (AUC=0.87), with 44% PPV and 96% NPV at 1.0% cutoff.
• Median dd-cfDNA levels were elevated in antibody-mediated rejection (2.9%) and significant T cell-mediated rejection (1.2%) compared to controls (0.3%).

Conclusions:

• Plasma dd-cfDNA is a valuable noninvasive tool for assessing kidney allograft rejection and injury.
• dd-cfDNA levels below 1.0% suggest the absence of active rejection (T cell-mediated ≥IB or ABMR).
• dd-cfDNA levels above 1.0% indicate a probability of active allograft rejection, warranting further investigation.