Abstract
Rejection following liver and kidney transplantation remains a major barrier to long-term graft survival. Early and reliable detection of rejection is crucial for optimizing patient outcomes and guiding personalized therapeutic approaches. Despite ongoing efforts, currently available serum-based biomarkers often fail to provide sufficient sensitivity and specificity for early diagnosis. Dickkopf-1 (DKK1) and cytoskeleton-associated protein 4 (CKAP4) are molecules involved in Wnt signaling, immune regulation, fibrosis, and tissue remodeling. Their upregulation has been associated with inflammatory and fibrotic processes in various pathological contexts. These properties make them strong candidates as novel molecular biomarkers in transplant rejection. This prospective observational study aimed to investigate the association between DKK1 and CKAP4 mRNA expression levels and the occurrence of rejection in liver and kidney transplant recipients. Peripheral blood samples from 55 transplant patients diagnosed with rejection (30 kidney, 25 liver) and 35 healthy controls were analyzed for DKK1 and CKAP4 mRNA expression using real-time polymerase chain reaction. Expression profiles were evaluated in relation to clinical and histopathological parameters. DKK1 and CKAP4 mRNA expression levels were significantly elevated in transplant recipients with rejection compared with healthy controls. In kidney transplant patients, both markers showed increased expression, although no significant histopathological correlations were detected. In liver transplant recipients, DKK1 expression was significantly associated with cellular rejection and portal inflammation. These findings suggest that DKK1 and CKAP4 may serve as promising molecular biomarkers for transplant rejection monitoring. In particular, DKK1 may provide additional diagnostic value in identifying cellular rejection and portal inflammation in liver grafts. Further multicenter studies are required to validate these results and assess their potential for clinical application.