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Updated: Mar 3, 2026
Robot-Assisted Kidney Transplantation
Published on: July 19, 2021
Risk stratification by donor-derived cell-free DNA: a three-year single center study of kidney transplant outcomes
Rhys Mendel1, Kabir Jalal2, Lin Liu3
1Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States.
Insights
Donor-derived cell-free DNA (dd-cfDNA) is a valuable biomarker for kidney transplant recipients. Elevated dd-cfDNA levels indicate increased alloimmune activity, rejection risk, and reduced graft survival.
Area of Science:
- Nephrology
- Transplant Immunology
- Biomarker Discovery
Background:
- Donor-derived cell-free DNA (dd-cfDNA) is an established blood biomarker for assessing alloimmune activity post-kidney transplantation.
- Monitoring dd-cfDNA aids in understanding the immune response against the transplanted kidney.
Purpose of the Study:
- To evaluate the association between dd-cfDNA levels and kidney graft function and survival.
- To explore relationships between dd-cfDNA levels and rejection, donor-specific antibodies (DSAs), C4d deposition, and eGFR trajectories.
Main Methods:
- Retrospective study of 257 kidney transplant recipients with dd-cfDNA measurements over 3 years.
- Patients stratified into three groups based on highest dd-cfDNA levels: <0.50%, 0.50-0.99%, and ≥1.0%.
- Analysis of graft function, survival, rejection rates, DSAs, C4d, and eGFR trends.
Main Results:
- The ≥1.0% dd-cfDNA group showed higher rejection rates, severe histopathologic injury, and more DSAs.
- The 0.50-0.99% dd-cfDNA group exhibited greater eGFR variability and decline.
- Higher dd-cfDNA levels were linked to decreased graft function and survival in multivariable modeling.
Conclusions:
- Elevated dd-cfDNA levels correlate with adverse alloimmune and functional outcomes, including rejection and reduced graft survival.
- eGFR decline in the >1.0% dd-cfDNA group predicted long-term graft failure and patient survival.
- dd-cfDNA is a clinically valuable biomarker for alloimmune risk stratification in kidney transplant recipients.
Background:
Donor-derived cell-free DNA is an established blood-based biomarker used to assess alloimmune activity after kidney transplantation.
Methods:
We performed a retrospective study of 257 kidney transplant recipients that had at least one dd-cfDNA measurements during 3-year period. The primary aim was to assess the association between dd-cfDNA levels with graft function and survival. Secondary exploratory aims included examining the relationships between dd-cfDNA strata and biopsy-proven rejection, donor-specific antibodies, C4d deposition, and longitudinal eGFR trajectories. Patients were stratified by their highest dd-cfDNA measurement into three groups: <0.50%, 0.50-0.99%, and ≥1.0%.
Results:
Patients categorized in the ≥1.0% dd-cfDNA group had increased rates of rejection, more severe histopathologic injury, and a higher prevalence of DSAs. With the ≥ 0.50-0.90% dd-cfDNA group having greater variability and decline in eGFR over the 3 year period. In exploratory multivariable modeling, higher dd-cfDNA strata were associated with a decline in graft function and survival.
Conclusions:
Elevated dd-cfDNA levels were associated with adverse alloimmune and functional outcomes, including rejection, DSA positivity, and reduced graft survival (p=0.0071). A logistic regression model identified eGFR decline in the >1.0% group to predict long-term graft failure and patient survival (p=0.04). These findings support the clinical value of dd-cfDNA as a biomarker of alloimmune risk in kidney transplant recipients.
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