Prognostic value of the donor-derived cell-free DNA assay in acute renal rejection therapy: A prospective cohort study.

Abstract

Donor-derived cell-free DNA (dd-cfDNA) is a promising biomarker for monitoring allograft status. However, whether dd-cfDNA can reflect real-time anti-rejection treatment effects remains unclear. We prospectively recruited 28 patients with acute renal rejection, including 5 with ABMR, 12 with type IA or type IB rejection, and 11 with type IIA or IIB rejection. dd-cfDNA levels in peripheral blood were measured using human single nucleotide polymorphism (SNP) locus capture hybridization. The percentage of dd-cfDNA (dd-cfDNA%) declined significantly from 2.566±0.549% to 0.773±0.116% (P<.001) after anti-rejection therapy. The dd-cfDNA% decreased steadily over the course of 3days with daily methylprednisolone injections, but no significant difference in the dd-cfDNA% was observed between the end of anti-rejection therapy and 2weeks later. Changes in the dd-cfDNA% (∆dd-cfDNA%) demonstrated a positive correlation with estimated glomerular filtration rates at 1month (ρ=2.570, P=.022), 3months (ρ=3.210, P=.027), and 6months (ρ=2.860, P=.019) after therapy. Thus, the dd-cfDNA assay shows prognostic capabilities in therapy outcome and allograft recovery; however, its ability is inhibited by methylprednisolone regardless of the types of rejection. Additionally, a reassessment of frequency intervals for testing is required.