35 - Detecting Subclinical Rejection using dd-cfDNA in Pediatric Kidney Transplant
Saturday, April 23, 2022
3:30 PM – 6:00 PM US MT
Poster Number: 35 Publication Number: 35.235
Auda M. Plaud Gonzalez, University of Puerto Rico School of Medicine, Carolina, Puerto Rico, United States; Nilka deJesus Gonzalez, University of Puerto Rico School of Medicine, San Juan, Puerto Rico, United States
Assistant Professor University of Puerto Rico School of Medicine Carolina, Puerto Rico, United States
Background: Detection of subclinical kidney transplant(KTx) rejection by surveillance biopsies and early management improves graft survival. However, these are cumbersome and invasive. Donor derived cell free DNA(dd-cfDNA) has emerged as a tool to predict KTx rejection in adult patients when >1% is present. Limited data is available in pediatrics.
Objective: We aimed to determine whether surveillance with dd-cfDNA detects subclinical KTx rejection in children using a threshold >1%.
Design/Methods: Retrospective chart review of all patients(n=30) followed at a single pediatric KTx program from 1/2021-12/2021. Patients with multiorgan transplant(n=2) and without dd-cfDNA(n=1) were excluded. dd-cfDNA was performed as surveillance, starting on 12/2020(every 3-6months). dd-cfDNA, demographics, eGFR, BK status, donor specific antibodies(DSA) and biopsy(Bx) findings(Banff 2019 criteria) were collected. Descriptive statistics and diagnostic test validity assessments were performed. Rejection outcome(for diagnostic validity testing) was defined as any of these: borderline T-cell mediated rejection(bTCMR), TCMR, antibody mediated rejection(ABMR), or mixed.
Results: During study period, 27 patients had dd-cfDNA performed(ESKD cause: 65%CAKUT, 31%GN; sex: 27%female; age at KTx: 12yrs; baseline egfr: 87 ml/min/1.73m2 [IQR 78-96]). Post KTx time at dd-cfDNA evaluations: 30%(n=8) < 1yr, 33%(n=9) 1-3yrs, 37%(n=10) > 3yrs. 11 patients had dd-cfDNA >1%; two of them were not biopsied(1 had BK viremia, dd-cfDNA decreased < 1% after lowering immunosuppression(IST); 1 had DSAs and abnormal coagulations, dd-cfDNA decreased < 1% after increasing maintenance IST). 44% of patients(12/27) had a biopsy: 9 with dd-cfDNA >1% (median 1.8% [IQR 1.6-3.2%]; Bx findings: 3 TCMR, 4 bTCMR, 2 mixed rejection) and 3 with dd-cfDNA < 1%, performed due to another indication(AKI=2 and BK viremia=1; median 0.78%[IQR 0.7-0.8%]; Bx findings: 1 bTCMR, 1 TCMR and 1 normal). dd-cfDNA >1% had a 100% specificity and 81.8% sensitivity(AUC: 0.909) to diagnose rejection. In patients with dd-cfDNA < 1% and no Bx, median dd-cfDNA was 0.23%[IQR 0.16-0.42%].Conclusion(s): Subclinical rejection was detected using dd-cfDNA >1% in this cohort with high specificity/sensitivity, supporting its potential use as a graft rejection surveillance tool. Two patients had dd-cfDNA < 1% and rejection suggesting that lower cut-offs may be needed to enhance detection. Given the small sample size and low ABMR prevalence in this cohort, we were unable to assess whether dd-cfDNA discriminates between rejection types. Validation of dd-cfDNA is needed in larger scale pediatric studies.