Challenges of Diagnosing Antibody-Mediated Rejection: The Role of Invasive and Non-Invasive Biomarkers

Abstract

Kidney transplantation is the best treatment modality for end-stage kidney disease, leading to improvement in a patient’s quality and quantity of life. With significant improvements in short-term outcomes, prolonging long-term allograft and patient survival remain ongoing challenges. The ability to monitor allograft function, immune tolerance and predict rejection accurately would enable personalization and better prognostication during post-transplant care. Though kidney biopsy remains the backbone of transplant diagnostics, emerging biomarkers can help detecting kidney allograft injury early enough to prevent permanent damage and detect injury before it is clinically apparent. In this review, we summarize the recent biomarkers that have shown promise in the prediction of acute rejection with a focus on antibody-mediated rejection in kidney transplantation.

Extracellular vesicles: a potential new player in antibody-mediated rejection in lung allograft recipients

“…As per ISHLT consensus on pulmonary AMR ( 25 ), a diagnosis of allograft dysfunction requires histologic evidence, complement component 4d (C4d) deposition, circulating DSAs, and the reasonable exclusion of other causes ( 11 , 17 ). Although histology remains a popular diagnostic approach, new noninvasive methods involving blood (DSAs, donor-derived cell-free DNA, mRNA assays) or urine (chemokines, urinary mRNA, and urinary proteomics) are also becoming popular ( 5 , 27 , 42 ). We have summarized AMR diagnosis with invasive and non-invasive methods and treatments in Table 1 .…”

“…Therefore, it is important to devlop modern diagnostic techniques to determine AMR. One emerging possibility, in addition to C4d staining, is non-invasive molecular diagnostics ( 27 , 42 ).…”

Understanding Donor-derived Cell-free DNA in Kidney Transplantation: An Overview and Case-based Guide for Clinicians

“…[10][11][12] The search for a rejection biomarker that is not only better than serum creatinine but also sensitive, specific, noninvasive, inexpensive, rapidly obtained, repeatable, and independent of patient and transplant characteristics has been documented widely in the literature. [13][14][15][16][17] Many candidate biomarkers have failed to navigate the stringent validation process required for implementation in clinical care or have failed to garner the enthusiasm of clinicians necessary to permit widespread clinical adoption. Biomarker performance is dependent on the clinical context.…”

“…10-12 The search for a rejection biomarker that is not only better than serum creatinine but also sensitive, specific, noninvasive, inexpensive, rapidly obtained, repeatable, and independent of patient and transplant characteristics has been documented widely in the literature. 13-17…”

An Antibody-Aptamer-Hybrid Lateral Flow Assay for Detection of CXCL9 in Antibody-Mediated Rejection after Kidney Transplantation

“…C4d deposition of peritubular capillaries in transplant biopsies were also not consistently associated with the full histopathological finding of AMR [ 12 , 13 ]. Thus, an alternative easy and cheap diagnostic for recognition of AMR is urgently needed based upon biomarkers with high specificity for AMR [ 14 , 15 ].…”