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Biomarkers and immune monitoring

Tuesday September 24, 2024 - 10:40 to 12:10

Room: Emirgan 1

321.2 Clinical utility of donor-derived cell-free DNA during the period of recovery of renal function after kidney transplantation

Pedro H. Oliveira Sr., Brazil

Clinical Research
Hospital do Rim - Fundação Oswaldo Ramos

Abstract

Clinical utility of donor-derived cell-free DNA during the period of recovery of renal function after kidney transplantation

Pedro Oliveira1, Monica Rika Nakamura1,2, Paulo Pierry3, Renata Glehn-Ponsirenas4, Silvia Casas4, José Levi3, Renato Foresto1,2, Jose Medina-Pestana1,2, Helio Tedesco-Silva1,2.

1Hospital do Rim , Fundação Oswaldo Ramos, São Paulo, Brazil; 2Nephrology Division , Universidade Federal de São Paulo, São Paulo, Brazil; 3DASA, São Paulo, Brazil; 4CareDX, Brisbane, CA, United States

Introduction: High Kidney Donor Profile Index (KDPI) and delayed graft function (DGF) duration are risk factors associated with incomplete recovery of kidney function (IRKF). Kidney biopsies are essential to exclude the diagnosis of acute rejection (AR). This study evaluates the clinical utility of monitoring donor-derived cell-free DNA (dd-cfDNA), a kidney injury biomarker, in recipients of high KDPI during kidney function recovery.
Methods: This is a single-center, prospective cohort study in recipients with a high risk of developing DGF, defined as the need for dialysis within the first week after transplantation. All patients received a single 3 mg/kg anti-thymocyte globulin dose, tacrolimus, mycophenolate, and prednisone. Blood samples were obtained at 14(D14) and 30(D30) days to measure the percentage of dd-cfDNA. The dd-cfDNA > 0.5% is associated with an increased probability of acute rejection (AR).
Results: This preliminary analysis includes data from 143 patients. The median KDPI was 63% [IQR 358], and the mean cold ischemia time was 24± 8 hours. The incidence of DGF was 76%, with a median duration of 4 [IQR 3-8] days.
At D14, the median GFR was 10 mL/min/1.73m2 (IQR 6-18). The median dd-cfDNA levels were 0.79% [IQR 0.51-1.20], with 109 patients (76%) showing dd-cfDNA ≥0.5%. Surveillance biopsies during DGF were performed in 69 (48%) patients showing 4 borderline changes (dd-cfDNA 0.57%, 0.98%, 2.90%, 3.30%), one T-cell mediated rejection IA (dd-cfDNA 0.41%), and 3 T-cell mediated rejection IIA (dd-cfDNA 0.21%, 0.52%, 0.57%). Using dd-cfDNA ≥0.5% to guide the indication of the surveillance biopsy, we would have avoided 16 (23%) biopsies but missed one patient with TCMR1A (dd-cfDNA 0.41%) and one patient with TCMR2A (dd-cfDNA 0.21%).
At D30, the median GFR was 33 mL/min/1.73m2 [IQR 23-47]. The median dd-cfDNA levels were 0.59% [IQR 0.40-0.80], with 88 patients (62%) showing dd-cfDNA ≥0.5%.  Surveillance biopsies performed in 22 (15%) patients with IRKF showed 3 borderline changes (ddcfDNA 0.17%, 0.67%, 2.80%), and 1 TCMR1A (dd-cfDNA 2.5%). Using dd-cfDNA ≥0.5% to guide the indication of the surveillance biopsy, we would have avoided 8 (36%) biopsies but missed 1 patient with borderline changes (dd-cfDNA 0.17%).
Conclusion: This preliminary analysis suggests that monitoring dd-cfDNA may assist clinical decisions during DGF and in kidney transplant recipients with incomplete recovery of graft function.

References:

[1] DGF
[2] ddcfDNA
[3] Kidney biopsies
[4] acute rejection
[5] Graft rejection
[6] Biomarkers
[7] delayed graft function
[8] kidney transplant

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