Introduction:
To improve acute rejection(AR) detection in pediatric renal transplants, we propose KidneyCare , combining AlloSure(donor-derived cell-free DNA) and AlloMap(gene expression profiling). AlloMap assesses 5 genes expression, generating a score of 0-20. AlloSure quantifies allograft tissue injury as a percentage of total circulating cell-free DNA.We suggest this combined approach may boost diagnostic accuracy and correlate with Banff lesion intensity
Methods:
In the study, 72 AlloSure and 69 AlloMap samples were collected prospectively pre-biopsy from 61 patients across 3 centers in the first year post-transplant
Assays were conducted at CareDx labs. Samples were categorized as AR or Quiescence. Area under the ROC assessed their ability to distinguish AR from quiescence. Principal component analysis condensed variables for logistic regression. Histology scores followed Banff 2018 update
Results:
In our study, comprising 18 AR biopsy specimens and 59 without AR, median AlloSure levels were significantly higher in the AR group (1.7%; IQR,0.42%–3.9%) compared to the quiescent group (0.28%; IQR,0.18%–0.46%). AlloMap scores were also significantly elevated in the AR group (median 13; IQR,12–14) compared to the quiescent group (median 9.9; IQR,8.2–11). The AUC for AlloSure alone to identify AR was 0.83, for AlloMap alone was 0.82, and the combined AUC improved to 0.94.
The combination of tests correctly predicted and potentially avoided 40 out of 41 biopsies. AlloSure levels increased with Banff lesions: from 0.77 ± 0.13% to 3.8 ± 0.52% for glomerulitis (G grades 1-2),0.44 ± 0.01% to 2.9 ± 2.1% for peritubular capillaritis (PTC grades 0-3),0.40 ± 0.05% to 3.0 ± 0.52% for interstitial inflammation (IF grades 0-3),0.51 ± 0.07% to 3.0 ± 0.8% for tubulitis grades 0-3,0.5 ± 0.1% to 2.6 ± 0.27% for interstitial fibrosis (IF grades 0-3), and 0.42 ± 0.8% to 3.9 ± 1.3% for tubular atrophy (TA grades 0-3). Similarly, AlloMap levels increased with Banff lesion severity: from 10 ± 2.8 to12 ± 1.6 for G1-2,9.8 ± 2.6 to14 ± 2.5 for PTC 0-3, 9.7 ± 2.1 to 14 ± 2.6 for IF0-3, 9.4 ± 2.1 to 13.0 ± 1.9 for tubulitis 0-3, 9.8 ± 2.9 to 14 ± 1 for IF 0-3, and 9.8 ± 2.8 to 13 ± 1.6 for TA 0-3.
Conclusions:
Combining AlloSure and AlloMap yields highly accurate AR assessment, correlating positively with allograft tissue injury severity
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.