Biomarkers of Rejection in Kidney Transplantation

Alloimmune injury is a major cause of long-term kidney allograft failure whether due to functionally stable (subclinical) or overt clinical rejection. These episodes may be mediated by immune cells (cellular rejection) or alloantibody (antibody-mediated rejection). Early recognition of immune injury is needed for timely appropriate intervention to maintain graft functional viability. However, the conventional measure of kidney function (ie, serum creatinine) is insufficient for immune monitoring due to limited sensitivity and specificity for rejection. As a result, there is need for biomarkers that more sensitively detect the immune response to the kidney allograft. Recently, several biomarkers have been clinically implemented into the care of kidney transplant recipients. These biomarkers attempt to achieve multiple goals including (1) more sensitive detection of clinical and subclinical rejection, (2) predicting impending rejection, (3) monitoring for the adequacy of treatment response, and (4) facilitating personalized immunosuppression. In this review, we summarize the findings to date in commercially available biomarkers, along with biomarkers approaching clinical implementation. While we discuss the analytical and clinical validity of these biomarkers, we identify the challenges and limitations to widespread biomarker use, including the need for biomarker-guided prospective studies to establish evidence of clinical utility of these new assays.