Proteomics for rejection diagnosis in renal transplant patients: Where are we now?

Abstract

Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allograft biopsies are not suitable for continuous monitoring of rejection. Thus, there is an unmet need for non-invasive methods to diagnose acute and chronic rejection. Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003. This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses. The potential limitations and open questions in establishing proteomic markers for rejection are discussed, including ongoing trials and future challenges to this topic.

Urinary Peptidomic Biomarkers in Kidney Diseases

“…Many proteomic studies have focused on graft rejection, given that, despite improvements in immunosuppressive therapy and patient surveillance after renal transplantation, allograft rejection remains a significant adverse factor for long-term graft survival [58]. Both T cell-mediated rejection and antibody-mediated rejection are leading causes of graft failure.…”

“…When evaluating the urinary peptidomic results, the biological significance of identified molecules and identification of the modulated processes which are involved form a key aspect. In a recent review on proteomic markers for T-cell mediated rejection, use of the pathway-and enzyme reaction-related Reactome information resource revealed processes related to platelet degranulation, lipid digestion, keratan sulphate degradation, antigen presentation and interferon gamma signaling to be directly associated with the input proteins [58]. More recently, Marx et al [67] used a semantic clustering approach to evaluate the molecular pathway and biological processes specific for different forms of renal allograft disease, including T cell-mediated rejection, antibody-mediated rejection, intestinal fibrosis and tubular atrophy, and polyomavirus-associated nephropathy.…”

Proteomics in Kidney Allograft Transplantation—Application of Molecular Pathway Analysis for Kidney Allograft Disease Phenotypic Biomarker Selection

“…A multitude of biomarkers have already been described for the main complications occurring after kidney transplantation, particularly for TCMR and AMR . Yet, there is an unmet need for better understanding of the mechanisms driving acute and chronic alloimmune injury, immunological quiescence, operational tolerance and tissue injury.…”

Urinary proteomics: fancy gadgetry or a clinically useful diagnostic instrument? The end-user's perspective

“…A vast number (hundreds to thousands) of different peptides are “fished” or “mined” from the urine, identified and sorted using sophisticated hardware and software tools. The differences in urine proteins according to the various etiologies provided by conventional methods allows establishing a group of marker proteins and peptides exhibiting different patterns depending on the pathomechanism which may be characteristic (similarly to a fingerprint) and potentially be used for disease detection and diagnostics .…”

“…This is especially true for children grafted with an adult kidney which by far overcomes the body's detoxification requirements. The presence of donor‐specific HLA antibodies again is not a fully reliable indicator of cABMR, since antibodies not pathogenic and not involved in the disease processes may be detected and vice versa, and histopathological features of cABMR may be present without detectable antibodies . Since the ultimate goal is early detection of rejection, some transplant centers perform protocol biopsies to evaluate the course of the allograft.…”