Bu Lihong, Gupta Gaurav, Pai Akshta, Anand Sanjiv, Stites Erik, Moinuddin Irfan, Bowers Victor, Jain Pranjal, Axelrod David A, Weir Matthew R, Wolf-Doty Theresa K, Zeng Jijiao, Tian Wenlan, Qu Kunbin, Woodward Robert, Dholakia Sham, De Golovine Aleskandra, Bromberg Jonathan S, Murad Haris, Alhamad Tarek
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
Division of Nephrology, Virginia Commonwealth University, Richmond, Virginia, USA.
Kidney Int. 2022 Apr;101(4):793-803. doi: 10.1016/j.kint.2021.11.034. Epub 2021 Dec 22.
The use of routine monitoring of donor-derived cell-free DNA (dd-cfDNA) after kidney transplant may allow clinicians to identify subclinical allograft injury and intervene prior to development of clinically evident graft injury. To evaluate this, data from 1092 kidney transplant recipients monitored for dd-cfDNA over a three-year period was analyzed to assess the association of dd-cfDNA with histologic evidence of allograft rejection. Elevation of dd-cfDNA (0.5% or more) was significantly correlated with clinical and subclinical allograft rejection. dd-cfDNA values of 0.5% or more were associated with a nearly three-fold increase in risk development of de novo donor-specific antibodies (hazard ratio 2.71) and were determined to be elevated a median of 91 days (interquartile range of 30-125 days) ahead of donor specific antibody identification. Persistently elevated dd-cfDNA (more than one result above the 0.5% threshold) predicted over a 25% decline in the estimated glomerular filtration rate over three years (hazard ratio 1.97). Therefore, routine monitoring of dd-cfDNA allowed early identification of clinically important graft injury. Biomarker monitoring complemented histology and traditional laboratory surveillance strategies as a prognostic marker and risk-stratification tool post-transplant. Thus, persistently low dd-cfDNA levels may accurately identify allograft quiescence or absence of injury, paving the way for personalization of immunosuppression trials.
肾移植后对供体来源的游离DNA（dd-cfDNA）进行常规监测，可能使临床医生能够识别亚临床同种异体移植损伤，并在临床明显的移植损伤发生之前进行干预。为评估这一点，分析了1092名肾移植受者在三年期间监测dd-cfDNA的数据，以评估dd-cfDNA与同种异体移植排斥组织学证据之间的关联。dd-cfDNA升高（0.5%或更高）与临床和亚临床同种异体移植排斥显著相关。dd-cfDNA值达到0.5%或更高与新发供体特异性抗体的风险增加近三倍相关（风险比2.71），并且在供体特异性抗体识别前中位数91天（四分位间距为30-125天）被确定为升高。持续升高的dd-cfDNA（超过一个结果高于0.5%阈值）预测三年期间估计肾小球滤过率下降超过25%（风险比1.97）。因此，对dd-cfDNA进行常规监测可早期识别临床上重要的移植损伤。生物标志物监测作为移植后的预后标志物和风险分层工具，补充了组织学和传统实验室监测策略。因此，持续低水平的dd-cfDNA可能准确识别同种异体移植的静止状态或无损伤，为免疫抑制试验的个性化铺平道路。
