1332 - Prognostic Significance of Early Donor-Derived Cell-Free DNA Elevations After Kidney Transplantation

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Author Block: K. Sureshkumar¹, J. Klein², D. Kumar³, N. Costa⁴, K. Sureshkumar¹, P. Chuang⁵, L. Shen⁵, J. Lu⁵, Y. Huang⁶, A. Wiseman⁷, E. Huang⁸, S. Knechtle⁹, S. Bunnapradist¹⁰, R. Villicana¹¹, P. Sood¹², N. Leca¹³, D. Mandelbrot¹⁴, J. S. Bromberg¹⁵, ¹Allegheny General Hospital, Pittsburgh, PA, ²University of Kansas, Leawood, KS, ³VCU, Richmond, VA, ⁴MedStar Georgetown, Washington, DC, ⁵CareDx, Brisbane, CA, ⁶UC Davis, Sacramento, CA, ⁷AdventHealth, Denver, CO, ⁸Cedas-Sinai, Los Angeles, CA, ⁹Duke University, Durham, NC, ¹⁰UCLA, Los Angeles, CA, ¹¹Loma Linda University, Loma Linda, CA, ¹²UCSF, San Francisco, CA, ¹³University of Washington, Seatle, WA, ¹⁴UW Health, Madison, WI, ¹⁵University of Maryland, Baltimore, MD
*Purpose: Early post-transplant dd-cfDNA elevations are frequently attributed to ischemia-reperfusion injury with unclear clinical implications. We evaluated whether dd-cfDNA trajectories during the first 4 months after kidney transplant were associated with long-term graft survival.
*Methods: Kidney transplant recipients (KTRs) from the Kidney Outcomes AlloSure® Registry (KOAR) with a first dd-cfDNA test between 15-60 days post-transplant and ≥2 results within 4 months were included. dd-cfDNA was elevated if ≥1% or 0.5-<1% with ≥61% relative change value. KTRs were classified by dd-cfDNA trajectory: low-low (no elevation), high-low (transient), low-high (late), and high-high (persistent). Outcomes assessed after month 4 were 3-year incidence of DSA, rejection, graft dysfunction (eGFR ≤30 mL/min/1.73 m²), and graft loss, with mortality as a competing risk.
*Results: Among 1,137 KTRs (low-low n=952; high-low n=111; low-high n=36; high-high n=38), the 3-year cumulative incidence of DSA, rejection, graft dysfunction, and graft loss were higher in patients who had dd-cfDNA elevation (Low-High, High-High) by Month-4 than those with normalized dd-cfDNA (High-Low, Low-Low) (Figure 1). Rejection occurred in 8.0%, 15.3%, 30.6%, and 47.4% of the Low-Low, High-Low, Low-High, and High-High groups, respectively (p<0.001). The risk of graft loss was highest with persistent elevation (High-Low HR 1.4 [0.4-4.8], p=0.58; Low-High HR 4.4 [1.3-15.2], p=0.018; High-High HR 11.2 [4.6-27.0], p<0.001; reference=Low-Low). Persistent dd-cfDNA elevation was associated with the highest event rates across all outcomes, whereas normalization (High-Low) yielded outcomes comparable to Low-Low.
*Conclusions: Early dd-cfDNA trajectories within the first 4 months post-transplant stratify long-term graft risk. Persistent elevation identifies KTRs at greater risk for DSA, rejection, graft dysfunction, and graft loss, while normalization reflects immune recovery and favorable prognosis.