Rejection markers in kidney transplantation: do new technologies help children?

Recent insights in allorecognition and graft rejection mechanisms revealed a more complex picture than originally considered, involving multiple pathways of both adaptive and innate immune response, supplied by efficient inflammatory synergies. Current pillars of transplant monitoring are serum creatinine, proteinuria, and drug blood levels, which are considered as traditional markers, due to consolidated experience, low cost, and widespread availability. The most diffuse immunological biomarkers are donor-specific antibodies, which are included in routine post-transplant monitoring in many centers, although with some reproducibility issues and interpretation difficulties. Confirmed abnormalities in these traditional biomarkers raise the suspicion for rejection and guide the indication for graft biopsy, which is still considered the gold standard for rejection monitoring. Rapidly evolving new omic technologies have led to the identification of several novel biomarkers, which may change the landscape of transplant monitoring should their potential be confirmed. Among them, urinary chemokines and measurement of cell-free DNA of donor origin are perhaps the most promising. However, at the moment, these approaches remain highly expensive and cost-prohibitive in most settings, with limited clinical applicability; approachable costs upon technology investments would speed their integration. In addition, transcriptomics, metabolomics, proteomics, and the study of blood and urinary extracellular vesicles have the potential for early identification of subclinical rejection with high sensitivity and specificity, good reproducibility, and for gaining predictive value in an affordable cost setting. In the near future, information derived from these new biomarkers is expected to integrate traditional tools in routine use, allowing identification of rejection prior to clinical manifestations and timely therapeutic intervention. This review will discuss traditional, novel, and invasive and non-invasive biomarkers, underlining their strengths, limitations, and present or future applications in children.

Automated summary

Recent insights have revealed that the process of allorecognition and graft rejection in transplantation involves multiple pathways of both adaptive and innate immune response. Traditional markers for transplant monitoring, such as serum creatinine, proteinuria, and drug blood levels, are widely used due to their affordability and availability. Donor-specific antibodies, the most common immunological biomarkers, are included in routine post-transplant monitoring but have some reproducibility issues. New omic technologies have led to the identification of novel biomarkers, including urinary chemokines and cell-free DNA of donor origin, which show promise but are currently expensive. Transcriptomics, metabolomics, proteomics, and the study of extracellular vesicles also have the potential for early identification of rejection in a cost-effective manner. These new biomarkers are expected to integrate with traditional tools for improved rejection detection and timely intervention.