Chandar Jayanthi, Sigurjonsdottir Vaka, Defreitas Marissa, Gavcovich Tara, Zhou Mingming, Glehn-Ponsirenas Renata, Burke George
Department, of Pediatrics, Division of Pediatric Nephrology, University of Miami Miller School of Medicine, Miami, FL, USA.
Miami Transplant Institute, Jackson Health System, Miami, FL, USA.
Pediatr Nephrol. 2025 Apr 14. doi: 10.1007/s00467-025-06770-w.
We describe our single-center experience in performing donor-derived cell-free DNA (dd-cfDNA) testing for a clinical indication in pediatric kidney transplant recipients.
Dd-cfDNA was done for increase in creatinine, appearance of de novo anti-HLA antibodies (dnHLAab) and for a clinical indication. We compared clinical characteristics of patients with dd-cfDNA > 1 with those with dd-cfDNA ≤ 1 and also compared dd-cfDNA in patients with no biopsy proven rejection (BPAR) or dnHLAab with those with BPAR, and those with dnHLAab and no BPAR.
Chart review was performed in 106 patients with a mean age of 11.0 ± 5.5 years. When compared with 62 patients with dd-cfDNA ≤ 1, 59.0% (26/44) of patients with dd-cfDNA > 1 had BPAR (OR 13.5: 95%CI 4.6,38; p < 0.0001), and 88.1% (37/44) had dnHLAab (OR 60.3 95%CI 17.2,192.2; p < 0.0001). Patients with DQ and DR dnHLAab (OR 115.2: 95%CI 24.8, 509.5; p < 0.0001) and those with donor-specific antibodies (DSAs) (OR 50.8: 95%CI 13.0, 168.7; p < 0.0001) were likely to have dd-cfDNA > 1. A repeated measures linear mixed effect model revealed a significant difference in dd-cfDNA between those with no antibodies or BPAR (p < 0.0001) and patients with BPAR and dnHLAab, with or without DSA. At the end of the follow-up period, eGFR was 72 mL/min/1.73 m in those without BPAR or dnHLAab and was significantly different from those with BPAR (eGFR 51 mL/min/1.73 m (p < 0.0001).
Elevated dd-cfDNA is strongly associated with BPAR, class II dnHLAab and DSAs. Conversely, low values are observed in immunoquiescent states. Dd-cfDNA can be a useful tool for non-invasive clinical decision-making.
我们描述了在儿科肾移植受者中进行供体来源的游离DNA（dd-cfDNA）检测以获得临床指征的单中心经验。
对肌酐升高、出现新发抗HLA抗体（dnHLAab）以及出于临床指征进行dd-cfDNA检测。我们比较了dd-cfDNA>1的患者与dd-cfDNA≤1的患者的临床特征，还比较了未活检证实排斥反应（BPAR）或dnHLAab的患者与有BPAR的患者以及有dnHLAab但无BPAR的患者的dd-cfDNA。
对106例平均年龄为11.0±5.5岁的患者进行了病历审查。与62例dd-cfDNA≤1的患者相比，dd-cfDNA>1的患者中有59.0%（26/44）发生了BPAR（比值比13.5：95%置信区间4.6,38；p<0.0001），88.1%（37/44）有dnHLAab（比值比60.3 95%置信区间17.2,192.2；p<0.0001）。有DQ和DR dnHLAab的患者（比值比115.2：95%置信区间24.8,509.5；p<0.0001）以及有供体特异性抗体（DSA）的患者（比值比50.8：95%置信区间13.0,168.7；p<0.0001）更有可能dd-cfDNA>1。重复测量线性混合效应模型显示，无抗体或BPAR的患者与有BPAR和dnHLAab的患者（无论有无DSA）之间的dd-cfDNA存在显著差异（p<0.0001）。在随访期末，无BPAR或dnHLAab的患者的估算肾小球滤过率（eGFR）为72 mL/min/1.73 m²，与有BPAR的患者（eGFR 51 mL/min/1.73 m²，p<0.0001）有显著差异。
dd-cfDNA升高与BPAR、II类dnHLAab和DSA密切相关。相反，在免疫静止状态下观察到低值。dd-cfDNA可成为无创临床决策的有用工具。
