初步探索程序性GcfDNA检测在肾移植中的意义

To explore the significance of programmed GcfDNA detection in renal transplantation

目的供体来源的cfDNA(graft-derived cell-free DNA,GcfDNA)作为一种有前途的无创生物标志物,一系列研究已证明其在检测移植排斥反应中的应用价值。然而,在肾移植后,尚无关于程序性检测GcfDNA的报道。随访期监测GcfDNA是否能指导临床工作,尚不得知。方法前瞻性采集了亲体肾移植和尸体肾移植受者术后第10天(D10)、第1个月(M1)、第3个月(M3)以及第6个月(M6)的GcfDNA拷贝数和百分比,并同期收集受者的临床资料,以作队列研究。结果共纳入87例受者,在D10的GcfDNA拷贝数为0.70 cp/ml,显著高于M1的0.40 cp/ml,GcfDNA百分比在M1为0.5%,显著高于M3的0.3%,但肌酐和肾小球滤过率在不同的时间点均无显著性差异。组间比较显示,亲体移植组的GcfDNA拷贝数在D10显著低于尸体移植组(0.45 cp/ml比0.90 cp/ml, P <0.05)。而两组受者的GcfDNA百分比在D10无显著性差异。将GcfDNA拷贝数和百分比与血清肌酐做回归分析,显示两者呈非线性相关。结论与肌酐或病理活检相比,GcfDNA拷贝数和GcfDNA百分比可作为评价肾功能的独立指标,同时GcfDNA水平与病理活检结果保持一致。缺血/再灌注损伤对GcfDNA的影响可持续到10 d以上,建议程序性检测在术后10 d启动。

Objective As a promising non-invasive biomarker, graft-derived cell-free DNA(GcfDNA) has been proved to be useful in detecting graft rejection in a series of studies. However, there has been no report on programmed detection of GcfDNA after renal transplantation. Whether GcfDNA monitoring during the follow-up period can guide clinical work is unknown. Methods The copy number and percentage of GcfDNA were prospectively collected from live donor kidney transplant recipients and cadaver kidney transplant recipients on day 10(D10), month 1(M1), month 3(M3), and month 6(M6) after surgery, and the clinical data of recipients were collected simultaneously for cohort study. Results A total of 87 recipients were enrolled, and the copy number of GcfDNA on D10 was 0.70 cp/ml, which was significantly higher than that on M1(0.40 cp/ml). The percentage of GcfDNA on M1 was 0.5%, which was significantly higher than that on M3(0.3%). However, there were no significant differences in creatinine and glomerular filtration rate at different time points. Group comparison showed that the GcfDNA copy number on D10 was lower in the live donor transplantation group than in the cadaver transplantation group(0.45 cp/ml vs. 0.90 cp/ml, P < 0.05). There was no significant difference in the percentage of GcfDNA between the two groups on D10. Regression analysis of GcfDNA copy number and percentage with serum creatinine showed a non-linear correlation. Conclusion GcfDNA copy number and percentage of GcfDNA are independent indicators of renal function compared with creatinine or pathological biopsy, and GcfDNA levels are in consistent with pathological biopsy results. The effect of ischemia reperfusion injury on GcfDNA can last for more than 10 days, so we recommend initiating programmed detection 10 days after surgery.