Ventura Abreu Aguiarà, PedroRamírez Bajo, María JoséRovira Juárez, JordiBañón Maneus, ElisendaHierro García, NataliaLazo Rodríguez, MartaCuatrecasas Freixas, MiriamGarcia Criado, María ÁngelesLiang, NathanSwenerton, Ryan K.Cofán Pujol, FedericoCucchiari, DavidEsforzado, NúriaMontagud Marrahi, EnriqueOppenheimer Salinas, FedericoPiñeiro, Gastón JulioRevuelta Vicente, IgnacioTorregrosa, VicensAhmed, EbadSoboleva, KarinaKaur, NavchetanZimmermann, Bernhard G.Al Haj Baddar, NourDemko, Zachary P.Escrig, CesarTabriziani, HosseinGauthier, PhilippeBillings, Paul R.Amor Fernández, Antonio JesúsFerrer Fábrega, JoanaCampistol Plana, Josep M.Diekmann, Fritz2025-12-022025-12-022022-08-010041-1337https://hdl.handle.net/2445/224584Background. Pancreas graft status in simultaneous pancreas-kidney transplant (SPKTx) is currently assessed by nonspecific biochemical markers, typically mylase or lipase. Identifying a noninvasive biomarker with good sensitivity in detecting early pancreas graft rejection could improve SPKTx management. Methods. Here, we developed a pilot study to explore donor-derived cell-free DNA (dd-cfDNA) performance in predicting biopsy-proven acute rejection (P-BPAR) of the pancreas graft in a cohort of 36 SPKTx recipients with biopsy-matched plasma samples. dd-cfDNA was measured using the Prospera test (Natera, Inc.) and reported both as a fraction of the total cfDNA (fraction; %) and as concentration in the recipient’s plasma (quantity; copies/mL). Results. In the absence of P-BPAR, dd-cfDNA was significantly higher in samples collected within the first 45 d after SPKTx compared with those measured afterward median, 1.00% versus 0.30%; median, 128.2 versus 35.3 cp/mL, respectively with both; P=0.001). In samples obtained beyond day 45, P-BPAR samples presented a significantly higher dd-cfDNA fraction (0.83 versus 0.30%; P=0.006) and quantity (81.3 versus 35.3 cp/mL; P=0.001) than stable samples. Incorporating dd-cfDNA quantity along with dd-cfDNA fraction outperformed dd-cfDNA fraction alone to detect active rejection. Notably, when using a quantity cutoff of 70 cp/mL, dd-cfDNA detected P-BPAR with a sensitivity of 85.7% and a specificity of 93.7%, which was more accurate than current iomarkers (area under curve of 0.89 for dd-cfDNA (cp/ml) compared with 0.74 of lipase and 0.46 for amylase). Conclusions. dd-cfDNA measurement through a simple noninvasive blood test could be incorporated into clinical practice to help inform graft management in SPKTx patients.8 p.application/pdfengcc-by-nc-nd (c) Ventura Abreu Aguiarà, Pedro et al., 2022https://creativecommons.org/licenses/by-nc-nd/4.0/Malalties del pàncreesMarcadors bioquímicsImmunologia de la trasplantacióPancréas diseasesBiochemical markersTransplantation immunologyinfo:eu-repo/semantics/article2025-10-30info:eu-repo/semantics/openAccess930055235289777