Wei Liang, Zhao Yongheng, Deng Shaoping, Wu Shaoping, Wang Hailian, Luo Xiangwei, Yang Hongji
Transplantation Health Management Center, Sichuan Taikang Hospital, Chengdu, Sichuan, China.
Department of Radiology, Sichuan Taikang Hospital, Chengdu, Sichuan, China.
Front Physiol. 2024 Nov 15;15:1440799. doi: 10.3389/fphys.2024.1440799. eCollection 2024.
The long-term graft survival is closely related to its early status, yet the indices for assessing the early graft status are complex and lack quantitative values. The aim of this study is to investigate the potential of GcfDNA as a comprehensive, non-invasive, convenient, and quantifiable indicator for evaluating early graft status.
In this study, 138 recipients who underwent primary kidney transplantation were enrolled. Peripheral blood samples, each 10 mL, were collected on days 1 and 7 post-transplantation. The quantification of both the graft cell-free DNA (GcfDNA) fraction (%) and GcfDNA concentration (copies per milliliter, cp/mL) was performed using droplet digital PCR (ddPCR).
For most recipients, both the GcfDNA fraction and concentration had a rapid decline at 7 days post-transplantation, reaching median values of approximately 0.7% and 53.5 cp/mL, respectively. No significant associations were found between GcfDNA values and other clinical parameters. On the seventh postoperative day, we observed a significant elevation in GcfDNA concentration among recipients with eGFR values < 60 mL/min/1.73 m. Additionally, notable increases were identified in both GcfDNA fraction and concentration variations within this specific subgroup. The findings of our study indicate a negative correlation between the concentration and fractional changes of GcfDNA on postoperative days 1 and 7, as well as the GcfDNA concentration on postoperative day 7, with eGFR within the 1-2 years post-transplantation period. The ROC curve of GcfDNA_Copies_Variation. day1-day 7 showed the highest AUC value AUC = 0.8006, with high sensitivity (90.14%) and specificity (77.61%), and PPV and NPV were 81.01% and 88.14%, respectively. Using four classical algorithm models, we found that the xgboost regression model achieved the best predictive performance (area under the curve (AUC) values = 0.862) for eGFR within 1-2 years post-transplantation, with high sensitivity (85.7%) and specificity (85%).
The changes of GcfDNA levels in the early stage are closely related to kidney function within 1-2 years post-transplantation. As a comprehensive indicator of graft function, GcfDNA has great potential for clinical application.
移植物的长期存活与早期状态密切相关，然而评估移植物早期状态的指标复杂且缺乏量化值。本研究的目的是探讨游离移植肾细胞DNA（GcfDNA）作为评估早期移植物状态的一种全面、无创、便捷且可量化指标的潜力。
本研究纳入了138例行初次肾移植的受者。在移植后第1天和第7天采集外周血样本，每份10 mL。使用液滴数字PCR（ddPCR）对移植物游离DNA（GcfDNA）分数（%）和GcfDNA浓度（每毫升拷贝数，cp/mL）进行定量分析。
对于大多数受者，GcfDNA分数和浓度在移植后第7天均迅速下降，中位数分别约为0.7%和53.5 cp/mL。未发现GcfDNA值与其他临床参数之间存在显著关联。在术后第7天，我们观察到估算肾小球滤过率（eGFR）值<60 mL/min/1.73 m²的受者中GcfDNA浓度显著升高。此外，在该特定亚组中，GcfDNA分数和浓度变化均有明显增加。我们的研究结果表明，移植后第1天和第7天GcfDNA的浓度和分数变化以及术后第7天的GcfDNA浓度与移植后1 - 2年内的eGFR呈负相关。GcfDNA_Copies_Variation.day1 - day 7的ROC曲线显示最高曲线下面积（AUC）值AUC = 0.8006，敏感性高（90.14%），特异性高（77.61%），阳性预测值（PPV）和阴性预测值（NPV）分别为81.01%和88.14%。使用四种经典算法模型，我们发现XGBoost回归模型对移植后1 - 2年内的eGFR具有最佳预测性能（曲线下面积（AUC）值 = 0.862），敏感性高（85.7%），特异性高（85%）。
早期GcfDNA水平的变化与移植后1 - 2年内的肾功能密切相关。作为移植物功能的综合指标，GcfDNA在临床应用中具有巨大潜力。
