Huang Edmund, Haas Mark, Gillespie Matt, Sethi Supreet, Peng Alice, Najjar Reiad, Vo Ashley, Jordan Stanley C
Department of Medicine, Division of Nephrology, Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, CA.
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
Transplantation. 2023 Jan 1;107(1):274-282. doi: 10.1097/TP.0000000000004267. Epub 2022 Aug 1.
Donor-derived cell-free DNA (dd-cfDNA) is a biomarker validated to detect rejection when measured to assess kidney allograft dysfunction. However, it remains unclear whether routine surveillance with dd-cfDNA provides additional information over standard monitoring of kidney allografts with creatinine and donor-specific antibodies (DSAs), particularly among those with little suspicion of rejection or injury. We investigated the value of measuring dd-cfDNA in patients with preserved allograft function and describe its association with future events.
Three-hundred seventeen kidney transplant recipients with a creatinine ≤1.5 mg/dL, no current DSA, and no prior rejection were assessed with dd-cfDNA and categorized into low (dd-cfDNA <0.5%; n = 239), moderate (dd-cfDNA 0.5% to <1.0%; n = 43), and high (dd-cfDNA ≥1.0%; n = 35) groups. The occurrence of rejection, DSA, graft loss, and change in estimated glomerular filtration rate over time after dd-cfDNA assessment was compared.
Over follow-up, rejections were more commonly found among patients with high vs low dd-cfDNA (17% versus 5%; P = 0.01); a similar nonsignificant trend was observed among patients with moderate compared to low dd-cfDNA (12% versus 5%; P = 0.13). DSA development was uncommon and not different between groups (low: 4%; moderate: 3%; high: 0%; P = 0.52). There was only 1 graft loss in a patient with low dd-cfDNA, and dd-cfDNA was not associated with graft dysfunction over time.
Most patients with elevated dd-cfDNA in conjunction with preserved allograft function remained stable over follow-up without deterioration in function or graft loss. Studies are needed to differentiate patients with elevated dd-cfDNA who will develop adverse outcomes from those who will remain clinically stable.
供体来源的游离DNA（dd-cfDNA）是一种生物标志物，经证实可在用于评估肾移植功能障碍时检测排斥反应。然而，与使用肌酐和供体特异性抗体（DSA）对肾移植进行标准监测相比，常规监测dd-cfDNA是否能提供更多信息仍不清楚，尤其是在那些几乎没有排斥或损伤嫌疑的患者中。我们研究了在移植肾功能良好的患者中检测dd-cfDNA的价值，并描述了其与未来事件的关联。
对317例肌酐≤1.5mg/dL、目前无DSA且既往无排斥反应的肾移植受者进行dd-cfDNA评估，并分为低（dd-cfDNA<0.5%；n=239）、中（dd-cfDNA 0.5%至<1.0%；n=43）、高（dd-cfDNA≥1.0%；n=35）三组。比较dd-cfDNA评估后随时间推移排斥反应、DSA、移植肾丢失及估计肾小球滤过率变化的发生情况。
随访期间，dd-cfDNA高组患者排斥反应的发生率高于低组（17%对5%；P=0.01）；dd-cfDNA中组与低组相比也观察到类似的无显著差异趋势（12%对5%；P=0.13）。DSA的发生并不常见，且各组之间无差异（低组：4%；中组：3%；高组：0%；P=0.52）。dd-cfDNA低组仅1例移植肾丢失，且dd-cfDNA与随时间推移的移植肾功能障碍无关。
大多数dd-cfDNA升高且移植肾功能良好的患者在随访期间保持稳定，功能无恶化或移植肾丢失。需要开展研究以区分dd-cfDNA升高且将出现不良结局的患者与临床保持稳定的患者。
