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Background <p>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.</p> Methods <p>Dd-cfDNA was done for increase in creatinine, appearance of de novo anti-HLA antibodies (<i>dn</i>HLAab) and for a clinical indication. We compared clinical characteristics of patients with dd-cfDNA &gt; 1 with those with dd-cfDNA ≤ 1 and also compared dd-cfDNA in patients with no biopsy proven rejection (BPAR) or <i>dn</i>HLAab with those with BPAR, and those with <i>dn</i>HLAab and no BPAR.</p> Results <p>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 &gt; 1 had BPAR (OR 13.5: 95%CI 4.6,38; <i>p</i> &lt; 0.0001), and 88.1% (37/44) had <i>dn</i>HLAab (OR 60.3 95%CI 17.2,192.2; <i>p</i> &lt; 0.0001). Patients with DQ and DR <i>dn</i>HLAab (OR 115.2: 95%CI 24.8, 509.5; <i>p</i> &lt; 0.0001) and those with donor-specific antibodies (DSAs) (OR 50.8: 95%CI 13.0, 168.7; <i>p</i> &lt; 0.0001) were likely to have dd-cfDNA &gt; 1. A repeated measures linear mixed effect model revealed a significant difference in dd-cfDNA between those with no antibodies or BPAR (<i>p</i> &lt; 0.0001) and patients with BPAR and <i>dn</i>HLAab, with or without DSA. At the end of the follow-up period, eGFR was 72 mL/min/1.73 m<sup>2</sup> in those without BPAR or <i>dn</i>HLAab and was significantly different from those with BPAR (eGFR 51 mL/min/1.73 m<sup>2</sup> (<i>p</i> &lt; 0.0001).</p> Conclusions <p>Elevated dd-cfDNA is strongly associated with BPAR, class II <i>dn</i>HLAab and DSAs. Conversely, low values are observed in immunoquiescent states. Dd-cfDNA can be a useful tool for non-invasive clinical decision-making.</p> Graphical abstract <p></p>

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Donor-derived cell-free DNA testing in pediatric kidney transplant recipients: indications and clinical utility

  • 期刊论文

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  • 发表日期：

    2025年4月14日

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  • Jayanthi Chandar,
  • Vaka Sigurjonsdottir,
  • Marissa Defreitas,
  • Tara Gavcovich,
  • Mingming Zhou,
  • Renata Glehn-Ponsirenas,
  • George Burke III

摘要

Background

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.

Methods

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.

Results

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 m2 in those without BPAR or dnHLAab and was significantly different from those with BPAR (eGFR 51 mL/min/1.73 m2 (p < 0.0001).

Conclusions

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.

Graphical abstract