*Purpose: Donor derived cell free DNA (dd-cfDNA) is increasingly used to predict acute rejection in kidney allografts . Cell free DNA fragments are constantly released into the circulation through cellular senescence and injury. DNA fragments are cleared from the blood by kidney and liver with a short half-life of around 30 minutes. It is unclear whether reduced estimated glomerular filtration rate (eGFR) in kidney transplant recipients (KTRs) would result in higher baseline dd-cfDNA values. We aimed to explore the variations in baseline dd-cfDNA at differing levels of eGFR in stable KTRs.

*Methods: Our center has been doing for-cause and surveillance (high immunologic risk) dd-cfDNA in KTRs using AlloSure (CareDx, Brisbane, CA). We identified patients who underwent kidney transplantation between September 2017 and June 2020 and had dd-cfDNA levels at or around 8 weeks post-transplantation. A dd-cfDNA value ≥ 1% prompted allograft biopsy. KTRs with biopsy evidence for rejection or other injuries were excluded from the analysis. Patients were divided based on GFR estimated with MDRD equation using 8-week serum creatinine (<30, 30-59 and ≥60 ml/min/1.73m²). Baseline 8-week dd-cfDNA levels were compared between different eGFR groups using t-test.

*Results: A total of 156 patients were identified during the study period. We excluded 36 patients with biopsy evidence of rejection from the analysis. The remaining 120 patients (66 males and 54 females) were available for the analysis including 11 with re-transplants. Among the study group, 40 patients had living and 80 had deceased donor kidney transplantation. Patients were stratified based on eGFR as follows: <30 ml/min/1.73m² (n=18), 30-59 ml/min/1.73m² (n=72), ≥60 ml/min/1.73m² (n=30). Baseline 8-week dd-cfDNA values were significantly higher in groups with eGFR <30 vs. ≥60 ml/min/1.73m² (0.74±0.65 vs. 0.25±0.12, p=0.005); <30 vs. 30-59 ml/min/1.73m² (0.74±0.65 vs. 0.38±0.34, p=0.03) and 30-59 vs. ≥60 ml/min/1.73m² (0.38±0.34 vs. 0.25±0.12, p=0.004). There was significant linear correlation between dd-cfDNA levels and eGFR as shown in figure 1.

*Conclusions: Our study found a significant correlation between baseline dd-cfDNA levels and decreasing eGFR. Higher levels of ongoing intra-graft inflammation and injury that could be associated with decreasing GFR is a plausible explanation for this finding. Decreased renal clearance of DNA fragments with declining GFR could also be contributory. These observations point towards the possible need for stratifying baseline dd-cfDNA based on the level of allograft function.

« Back to 2021 American Transplant Congress