Early Donor-Derived Cell-Free DNA Kinetics After Kidney Transplantation in Atypical Hemolytic Uremic Syndrome: A Preliminary Observational Study

Donor-derived cell-free DNA (dd-cfDNA) is an emerging non-invasive biomarker of kidney allograft injury. Elevated dd-cfDNA has been associated with acute rejection, particularly antibody-mediated rejection; however, dd-cfDNA reflects graft-derived tissue injury rather than a specific alloimmune mechanism. Its interpretation may therefore be challenging in conditions characterized by endothelial and microvascular injury, such as atypical hemolytic uremic syndrome (aHUS). This retrospective observational study included 14 kidney transplant recipients who underwent their first kidney transplantation at Wroclaw Medical University between April and December 2022. Twelve recipients without aHUS and two recipients with aHUS were assessed at day 7 (D7), day 14 (D14), month 1 (M1), and month 2 (M2). Protocol biopsies were not systematically performed. In recipients without aHUS, median %dd-cfDNA declined from 0.72% (range, 0.26–2.33%) at D7 to 0.12% (range, 0.05–0.34%) at M2. In the two recipients with aHUS, values remained near or above 1% through M1 and declined at M2. No donor-specific antibodies against human leukocyte antigens (HLA) or clinically documented rejection occurred. Exploratory analyses did not identify a statistically significant association between %dd-cfDNA and serum creatinine (Spearman rho = 0.09, p = 0.541). These recipient-level observations suggest that early dd-cfDNA kinetics in the two recipients with aHUS differed from the declining pattern in the small comparison cohort, but they do not establish a group-level difference. Because protocol biopsies were not systematically performed, subclinical rejection could not be excluded. The findings should be considered hypothesis-generating and support cautious interpretation of universal dd-cfDNA thresholds in aHUS.