Quantification of Postoperative Graft-Derived Cell-Free DNA to Evaluate the Risks of Impaired Allograft Function at Early Stage of Kidney Transplantation

Abstract

Graft-derived cell-free DNA (GcfDNA) is a promising biomarker for comprehensive monitoring of allograft injury because it overcomes the limitations of traditional approaches. The aim of this study is to investigate the association between the outliers of GcfDNA at initial time post transplantation and short-term renal graft function. A total of 230 recipients who underwent primary kidney transplantation were recruited in the study. For each recipient, 10 mL of peripheral blood were collected at day 1 post transplantation. Both of the GcfDNA fraction (%) and GcfDNA concentration (cp/mL) were determined using droplet digital PCR. The study was conducted in accordance with the 1964 Helsinki Declaration and its later amendments. There were no values that fall outside of the lower extreme in both of the GcfDNA fraction and GcfDNA concentration, and the upper fence of GcfDNA fraction and GcfDNA concentration were 13.5% and 680 cp/mL, respectively. Recipients with GcfDNA concentration ≥680 cp/mL had a statistically significant higher serum creatinine at day 7 post-transplantation, when compared with the other group (P=.008). The receiver operating characteristic analysis obtained an area under the curve value of 0.869 when using GcfDNA concentration to predict the risk of serum creatinine ≥400 μmol/L, an optimal cut-off value was indicated at 975 cp/mL with high sensitivity (87.5%) and specificity (85%). Our results suggest that the quantification of GcfDNA at initial time after transplantation might be used as a novel strategy for predicting short-term risk of impaired kidney allograft function or delayed graft function.