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Allograft Function and Baseline Donor-Derived Cell-Free DNA in Kidney Transplant Recipients: One Size Doesn’t Fit All
Corresponding author: Kalathil K Sureshkumar, Division of Nephrology and Hypertension, Medicine Institute, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA, United States. E mail: kalathil.sureshkumar@ahn.org
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Dear Editor,
Donor-derived cell-free DNA (dd-cfDNA) predicts acute rejection in kidney allografts.1-3 Cellular senescence and injury constantly release cfDNA fragments into circulation. DNA fragments are cleared from the blood by the kidneys and liver with a half-life of ∼30 minutes.4 It is unclear whether reduced estimated glomerular filtration rate (eGFR) in kidney transplant recipients (KTRs) would result in higher baseline dd-cfDNA values. Variations in baseline dd-cfDNA at different eGFRs in stable KTRs were explored in the current study.
We identified KTRs between September 2017 and June 2020 who had dd-cfDNA levels (AlloSure, CareDx, Brisbane, CA) 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. Patients were divided based on MDRD equation-based eGFR 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.
Among 156 patients, 36 with biopsy-proven rejection were excluded from the analysis. The remaining 120 (40 living and 80 deceased donor KTRs) 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 a significant linear correlation between dd-cfDNA levels and eGFR, as shown in Figure 1.
We found a significant correlation between baseline dd-cfDNA levels and eGFR. Decreasing renal clearance of DNA fragments and possibly higher levels of intra-graft inflammation with declining GFR are plausible explanations.5 These observations point towards the possible need for stratifying baseline dd-cfDNA based on the level of allograft function.
Acknowledgement
Presented virtually as a poster at American Transplant Congress 2021.
Financial support and sponsorship
Dr. Kalathil Sureshkumar and Dr. Bhavna Chopra received research grant from CareDx.
Conflicts of interest
There are no conflicts of interest.
The authors declare that no generative AI or AI-assisted tools were used in drafting, editing, or preparing this manuscript.
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