Abstract: SA-OR81
pOKRA Study: Biomarker-Based Diagnosis and Histological Correlation of Allograft Rejection in Pediatric Kidney Transplantation
Session Information
- Pediatric Nephrology: Insights and Innovations
October 26, 2024 | Location: Room 23, Convention Center
Abstract Time: 05:50 PM - 06:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Dharnidharka, Vikas R., Washington University in St Louis, St Louis, Missouri, United States
- Dandamudi, Raja, Washington University in St Louis, St Louis, Missouri, United States
- Agarwal, Mansi, Washington University in St Louis, St Louis, Missouri, United States
- Goss, Charles, Washington University in St Louis, St Louis, Missouri, United States
- Kelton, Megan, Seattle Children's Hospital, Seattle, Washington, United States
- Smith, Jodi M., Seattle Children's Hospital, Seattle, Washington, United States
Background
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.
Conclusion
Combining AlloSure and AlloMap yields highly accurate AR assessment, correlating positively with allograft tissue injury severity
Funding
- Commercial Support – American Society of Transplantation/ CareDx