Date: Monday, June 7, 2021
Session Time: 4:30pm-5:30pm
Presentation Time: 4:35pm-4:40pm
*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 August 3, 2021.
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