High Levels of Donor-Derived Cell-Free DNA Predict EGFR Decline After Kidney Transplantation
1Washington University in St. Louis, St. Louis, MO, 2Tampa General Hospital, Tampa, FL, 3University of Colorado, Aurora, CO, 4Intermountain Medical Center, Murray, UT, 5University of Maryland School of Medicine, Baltimore, MD, 6Virginia Commonwealth University, Richmond, VA, 7University of Minnesota, Minneapolis, MN, 8CareDx, Brisbane, CA, 9University of Texas McGovern Medical School, Houston, TX
Meeting: 2021 American Transplant Congress
Abstract number: 218
Keywords: Glomerular filtration rate (GFR), Graft survival, Kidney transplantation, Non-invasive diagnosis
Topic: Clinical Science » Biomarkers, Immune Assessment and Clinical Outcomes
Session Information
Session Name: Biomarkers, Immune Assessment and Clinical Outcomes - III
Session Type: Rapid Fire Oral Abstract
Date: Monday, June 7, 2021
Session Time: 4:30pm-5:30pm
Presentation Time: 4:35pm-4:40pm
Location: Virtual
*Purpose: Persistent, low-grade inflammation is associated with decline in eGFR. Cross-sectional studies have demonstrated a consistent association between circulating inflammatory markers and kidney function. Our objective was to assess whether donor-derived cell-free DNA (dd-cfDNA) as a marker of injury and inflammation is independently associated with longitudinal kidney transplant (KT) function decline.
*Methods: 1092 patients (2873 visits) were examined from the Assessing dd-cfDNA monitoring insights of renal allograft with longitudinal surveillance (ADMIRAL study; clinicaltrials.gov: NCT04566055219). Patients had dd-cfDNA (AlloSure®; CareDx, Inc.) during post-KT surveillance. Clinical events and Quant- BK PCR were monitored. High dd-cfDNA was defined as >0.5% based on analysis in ADMIRAL. K-means Clustering – an unsupervised machine learning algorithm was used to partition patients into similar clusters using key features such as race, gender, age at transplant, BK, dd-cfDNA, DSA and creatinine; reducing cohort to 219 patients. Intra-cluster noise reduction applied to only include patients with Δdd-cfDNA >60%. Each patient time-line weighted moving average (WMA) was applied to smooth eGFR and dd-cfDNA estimates.
*Results: K-means yielded 4 distinct clusters representing mean time post-KT of 4 months, 1, 3 and 10 years; frequency of patient visits ranged from 2-14. Over 1st year post-KT, there was a slight negative correlation for dd-cfDNA and eGFR (R:-0.11); however, there was a more significant decline over the initial 3-years (R:-0.84) (FIGURE 1). The 10-year cluster included a single patient, but manifested identical trend (R :-0.69).
*Conclusions: Although allograft dysfunction remains multifactorial, a high dd-cfDNA (>0.5%) level is associated with eGFR decline over the initial 3-years post-KT. Persistently elevated dd-cfDNA, a marker of injury and molecular inflammation, may indicate an increased risk of eGFR decline, thereby extending its utility beyond mere detection of acute clinical events. Therefore, dd-cfDNA surveillance after KT may add value to risk-stratify patients when considering long term outcomes and adjunctive therapies.
To cite this abstract in AMA style:
Alhamad T, Bowers V, Stites E, Anand S, Bromberg JS, Murad H, Gupta G, Moinuddin I, Bu L, Ghosh S, Zeng J, Pai A. High Levels of Donor-Derived Cell-Free DNA Predict EGFR Decline After Kidney Transplantation [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/high-levels-of-donor-derived-cell-free-dna-predict-egfr-decline-after-kidney-transplantation/. Accessed May 11, 2025.« Back to 2021 American Transplant Congress