Session Name: Biomarkers, Immune Assessment and Clinical Outcomes
Session Date & Time: None. Available on demand.
*Purpose: Dd-cfDNA is a validated plasma analyte (t½~30 min) for surveillance of renal transplant (KT) rejection with limited reports characterizing response to acute allograft rejection treatment.
*Methods: Prospective, serial dd-cfDNA plasma levels (AlloSure®) were collected at renal allograft biopsy & prior to each treatment throughout the course of therapy for KTs with biopsy-proven acute rejection (BPAR). Kinetics during treatment for Δdd-cfDNA(%) & ΔSCr(mg/dL) were analyzed from time of biopsy (T0) to treatment completion (T1) by Wilcoxon matched pairs signed rank (p<0.05). Simple linear regression (p<0.05) was performed for Δdd-cfDNA vs ΔSCr. Individual treatment responses were determined 4 – 12 weeks later & deemed “successful” if ΔSCr<20%.
*Results: Twelve KTs were analyzed median age 32 years (range 3-54). BPAR diagnoses included mixed [TCMR(1B-2B) + AbMR] (n=7), mixed [TCMR 1B+TMA] (n=1), AbMR (n=2), and TCMR 1B (n=2). Treatment included TPE (n=6), rATG(n=8), IVIG(n=6), rituximab(n=1), eculizumab(n=1), and steroids(n=12). A median of 6 (4 to 15) “treatment” dd-cfDNA levels were obtained per patient. Dd-cfDNA T0-T1 median of difference was 0.580% [p=0.007, median IQR 1.20% (0.245-3.575) το (T1) 0.665% (0.175-1.075)]. SCr T0-T1 median of difference was 0.075 mg/dL [p=0.11, median IQR (T0) 1.72 mg/dL (1.260-2.038) το (T1) 1.56 (0.965-1.78)]. ΔSCr vs Δdd-cfDNA revealed no statistical correlation (R2=0.165; p=0.17). Of subjects with f/u: 7/9 (77.8%) had “successful” ΔSCr responses at a median of 4 weeks (2 – 12); and although no correlation was determined, 8/9 (88.9%) treatment-related Δdd-cfDNA achieved T1 dd-cfDNA <1.0%, and 1/9 (11.1%) retained elevated SCr and dd-cfDNA. Four patients with stable SCr demonstrated worsening dd-cfDNA kinetics post-treatment of their initial rejection and revealed BPAR upon repeat biopsy. Early intervention in these patients did not allow progression to HLA-DSA formation or AbMR months after repeat treatment.
*Conclusions: This novel analysis of dd-cfDNA kinetics links decreasing dd-cfDNA levels with resolving “molecular injury” during effective immunomodulatory treatment of BPAR, despite a lack of significant ΔSCr improvement. The T1 dd-cfDNA levels had fallen to <1.0% for most subjects. Continued study is needed to investigate whether dd-cfDNA “treatment” kinetics can predict clinical outcomes of HLA-DSA escalation and/or chronic allograft loss. Dynamic kinetics of dd-cfDNA may present opportunity for patient-specific approaches to rejection treatment and earlier intervention that appears meaningful in preventing alloimmune response maturation to AbMR.
To cite this abstract in AMA style:Hinojosa R, Hitchman KM, Ross DJ, Hall RC, Nelson JE, Kincaide EL, Klein K, Bell AM. Real-time Donor-derived Cell-free Dna Kinetics Indicate Decreased “Molecular Injury” During Treatment of Acute Renal Allograft Rejection [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/real-time-donor-derived-cell-free-dna-kinetics-indicate-decreased-molecular-injury-during-treatment-of-acute-renal-allograft-rejection/. Accessed September 21, 2021.
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