dd-cfDNA is a biomarker for accurate diagnosis of kidney transplant antibody-mediated rejection (ABMR)

Recently, the Nephrology Center of the General Hospital of Eastern Theater Command collaborated with the AlloDx Medical Department, using the AlloDx AlloK seqTM [Ankang] non-invasive kidney transplant testing platform, to conduct a retrospective study on 50 patients with suspected rejection, revealing the value of donor-derived cell-free DNA (dd-cfDNA) in diagnosing antibody-mediated rejection in Chinese kidney transplant patients. The related results were published in the international authoritative transplantation journal Transplant Immunology.

In this retrospective observational study, 50 kidney transplant recipients diagnosed with suspected rejection at the General Hospital of Eastern Theater Command from June 2018 to May 2019 were enrolled, and plasma dd-cfDNA concentration was measured using the AlloK seqTM targeted capture sequencing method. Based on pathology (ABMR yes/no) and donor-specific antibody (DSA) results, patients were clinically divided into four groups: ABMR+/DSA+, ABMR+/DSA−, ABMR−/DSA+, and ABMR−/DSA−. Results showed the median dd-cfDNA concentration in the ABMR+ group (1.66%, IQR 1.34–3.76%) was significantly higher than in the ABMR− group (0.63%, IQR 0.43–0.74%; p < 0.001). ROC analysis yielded an AUC of 0.90 (95% CI 0.86–0.95); at a dd-cfDNA threshold of 0.96%, sensitivity was 90.5% (95% CI 69.6–98.8%), specificity 96.6% (95% CI 82.2–100%), PPV 95% (95% CI 73.4–99.2%), and NPV 93.3% (95% CI 78.9–98.1%). Accuracy far exceeded DSA for diagnosing ABMR (specificity 50%, sensitivity 74.1%, PPV 41.7%, NPV 80%). dd-cfDNA showed no significant difference between DSA+ and DSA− groups (p>0.05). The study suggests that regardless of DSA positivity, elevated dd-cfDNA may indicate ABMR, and dd-cfDNA can independently and precisely diagnose ABMR occurrence.

dd-cfDNA is a novel non-invasive diagnostic biomarker for organ transplantation. In kidney transplantation, it shows higher specificity and sensitivity than traditional markers (serum creatinine, antibodies, etc.). Since its clinical application in 2018, it has been routinely performed at kidney transplant centers abroad, with over 150,000 patients tested cumulatively. This study is the first to evaluate the value of AlloK seqTM in antibody-mediated rejection in a Chinese population, providing a precise non-invasive method for diagnosing rejection in Chinese kidney transplant patients.