*Purpose: A decline in estimated glomerular filtration rate (eGFR) during the first 12 months following kidney transplantation is associated with poor outcome and increased graft loss. Assessing whether elevation in donor-derived cell-free DNA (dd-cfDNA) is predictive of 2^nd year eGFR decline may help to predict long term outcome.

*Methods: 173 patients identified from the DART study had dd-cfDNA (AlloSure®) and eGFR measured 1-10 times during the first-year post transplant and 1-6 times during follow up visits during the second year. The mean eGFR results from year 2 were compared to the mean from year 1 (day 90-365) in patients with ≥1 elevated dd-cfDNA (AlloSure ≥1%) in the first year vs. those without dd-cfDNA elevation. Association between elevated dd-cfDNA (≥1%) and future events, defined as an instance of low eGFR below a target level of 15 – 30 ml/min/1.73m², were also tested. dd-cfDNA was also explored as a risk factor in a Cox proportional adjusted hazards model.

*Results: 33 patients with ≥1 elevated dd-cfDNA in days 90 – 365 were compared to 133 patients without dd-cfDNA elevation. 24/33 (73%) of patients with high 1^st year dd-cfDNA (≥1%) had a significant drop in eGFR in year 2 (median eGFR change -25%, IQR -46% to +2%) compared to 60/140 (45%) patients without elevated dd-cfDNA (median eGFR change +2%, IQR -18% to +45%), p = 0.002. dd-cfDNA ≥1% was associated with eGFR < 30 mL/min (p = 0.040, Chi Square test) and was a significant risk factor for eGFR below a threshold of 30 in the Cox model (p = 0.047), having a hazard ratio of 2.31 (95% CI 1.01 - 5.28).

*Conclusions: The cause of eGFR decline remains multifactorial; however, elevations in 1st year dd-cfDNA (≥1%) are associated with declining eGFR in year 2. dd-cfDNA may have utility beyond detecting acute events, and regular surveillance may be a useful tool in prediction of long term outcomes.

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