TABLE 2.
Summary of key literature reviewed on donor-derived cell-free DNA for clinical acute rejection.
| Authors | Study design | Number of samples | Results |
|---|---|---|---|
| [9] | Prospective observational, Multicenter | 107 biopsies | For any rejection (AUROC 0.74, PPV 0.61, NPV 0.84) |
| 27 rejections | |||
| 80 no rejection | |||
| [10] | Subgroup analysis of prospective observational, Multicenter | 87 patients | For ABMR with + DSA and dd-cfDNA >1%, (AUROC 0.86, PPV 0.81, NPV 0.83] |
| 16 ABMR | |||
| 53 no rejection | |||
| [2] | Retrospective analysis of biorepository samples, Single center | 217 biopsies | For any rejection for cause + SubAR (AUROC 0.87, PPV 0.52, NPV 0.95) |
| 38 rejections | |||
| 179 no rejection | |||
| [11] | Prospective observational, Single center | 63 biopsies | For any rejection (AUROC 0.71, PPV 0.77, NPV 0.75) |
| 34 rejections | |||
| 29 no rejection | |||
| [12] | Prospective observational, Single center | 189 patients | For any rejection (Absolute concentration of dd-cfDNA (AUROC 0.83) is better than dd-cfDNA (%) (AUROC 0.73) |
| 22 rejections | |||
| 395 stable samples | |||
| [13] | Prospective cross-sectional, Multicenter (n = 2) | 61 biopsies | For ABMR (absolute concentration AUROC 0.91 vs. dd-cfDNA (%) 0.89) |
| 13 ABMR | |||
| 48 no rejection | |||
| [14] | Subgroup analysis of prospective observational, Multicenter | 79 patients with TCMR 1A/borderline changes | Subjects with TCMR (1A and borderline) with high dd-cfDNA had worse clinical outcomes compared to those with low dd-cfDNA |
| [15] | Cross-sectional for DSA screening/Retrospective testing of dd-cfDNA on bio-banked samples, Single center | From 2 independent cohort | For ABMR with +DSA |
| 45/30 biopsies | AUROC for dd-cfDNA alone 0.89/0.69 | ||
| 25/17 ABMR | AUROC for DSA alone 0.88/0.77 | ||
| 20/13 no ABMR | |||
| [3] | Prospective observational, multicenter (ADMIRAL) | 219 biopsies | For any rejection dd-cfDNA (AUROC 0.8, PPV 0.5, NPV 0.9) |
| 113 rejections | |||
| 106 no rejection | |||
| [16] | Prospective observational, Single center | 208 biopsies | For any rejection dd-cfDNA and MMDx (AUROC 0.80), dd-cfDNA and histology (AUROC 0.75) |
| 162 rejections by histology | |||
| 46 no rejection by histology | |||
| [17] | Prospective observational, multicenter (TRIFECTA) | 300 biopsies | dd-cfDNA levels are strongly associated with the active molecular rejection phenotype (MMDx), particularly with AMR, mixed, and active TCMR |
| 120 rejections | |||
| 180 no rejection | |||
| [18] | Prospective observational, multicenter (TRIFECTA) | 367 biopsies | Any rejection prediction AUROC in test set by logistic regression model using both dd-cfDNA (%) and absolute concentration |
| 83 (histology test set) rejection | • 0.88 for MMDx | ||
| 71 (MMDx test set) rejection | • 0.82 for histologic rejection |
AUROC, area under the receiver operating characteristic curve; DSA, donor-specific antibody; MMDx, the molecular microscope diagnostic system; NPV, negative predictive value; PPV, positive predictive value.