Tuesday March 29, 2022 - 14:00 to 15:10
Use of donor-derived cell-free DNA assay to monitor treatment response in pediatric renal transplant recipients with allograft rejection
Dechu Puliyanda1, Justin Steggarda2, Helen Phan Pizzo1, Jonathan Garrison1, Xiaohai Zhang1, Mark Haas1, Irene K. Kim1, Stanley C. Jordan1.
1Comprehensive transplant center, Cedars Sinai Medical Center, Los Angeles, CA, United States; 2Transplant Surgery, Northwestern University, Chicago, IL, United States
Background: Donor-derived cell-free DNA (dd-cfDNA) may reliably detect allograft rejection in pediatric kidney transplant (KT) recipients. This study evaluates the utility of dd-cfDNA for monitoring treatment response amongst pediatric KT recipients suffering graft rejection.
Methods: Fifty-eight pediatric KT recipients were enrolled between April 2018 and March 2020 to undergo dd-cfDNA testing to monitor for rejection. Patients with dd-cfDNA scores >1.0% and biopsy-proven rejection formed the study cohort. Treatment for rejection consisted of intravenous immunoglobulin and rituximab, with or without pulse steroids or thymoglobulin. Results of dd-cfDNA, serum creatinine (SCr), biopsy results, and treatment and outcomes were evaluated. Standard statistical analyses were applied.
Results: Nineteen of 58 (31%) patients had dd-cfDNA score >1.0%, of which 18 (94.7%) were found to have rejection on biopsy. Mean dd-cfDNA value was 2.57±1.74% and biopsy results showed 11 patients (61.1%) with antibody mediated rejection (ABMR), 2 patients (11.1%) with T-cell mediated rejection (TCMR) and 5 patients (27.7%) with Mixed ABMR/TCMR. SCr at time of biopsy was 1.28±1.09 mg/dL. Following treatment, dd-cfDNA scores decreased for all types of rejection but remained >1.0% in both ABMR (1.97±1.13%) and Mixed (2.32±2.03%) groups. Mean dd-cfDNA value was lower for patients with TCMR (0.28±0.10%). SCr showed minimal change between pre- and post-treatment levels, regardless of rejection subtype.
Conclusions: Measurement of dd-cfDNA represents a potential method for early detection of rejection in pediatric KT recipients. Patients with TCMR may be reliably followed by dd-cfDNA; however, it remains unclear whether persistently elevated dd-cfDNA levels in patients with ABMR reflects ongoing subclinical rejection or an inherent limitation of the assay.