High-Throughput Proteomic Approaches to the Elucidation of Potential Biomarkers of Chronic Allograft Injury (CAI)

Abstract

This review focuses on the role of OMICs technologies, concentrating in particular on proteomics, in biomarker discovery in chronic allograft injury (CAI). CAI is the second most prevalent cause of allograft dysfunction and loss in the first decade post-transplantation, after death with functioning graft (DWFG). The term CAI, sometimes referred to as chronic allograft nephropathy (CAN), describes the deterioration of renal allograft function and structure as a result of immunological processes (chronic antibody-mediated rejection), and other non-immunological factors such as calcineurin inhibitor (CNI) induced nephrotoxicity, hypertension and infection. Current methods for assessing allograft function are costly, insensitive and invasive; traditional kidney function measurements such as serum creatinine and glomerular filtration rate (GFR) display poor predictive abilities, while the current “gold-standard” involving histological diagnosis with a renal biopsy presents its own inherent risks to the overall health of the allograft. As early as two years post-transplantation, protocol biopsies have shown more than 50% of allograft recipients have mild CAN; ten years post-transplantation more than 50% of the allograft recipients have progressed to severe CAN which is associated with diminishing graft function. Thus, there is a growing medical requirement for minimally invasive biomarkers capable of identifying the early stages of the disease which would allow for timely intervention. Proteomics involves the study of the expression, localization, function and interaction of the proteome. Proteomic technologies may be powerful tools used to identify novel biomarkers which would predict CAI in susceptible individuals. In this paper we will review the use of proteomics in the elucidation of novel predictive biomarkers of CAI in clinical, animal and in vitro studies.

Proteomics: Its Promise and Pitfalls in Shaping Precision Medicine in Solid Organ Transplantation

“…Prior observations suggested that a single biomarker is not likely to reflect the complex pathophysiological process in solid organ transplantation. 31,159 This notion, combined with the advent of a plethora of computational methods, has justified the preference toward the development of proteomic classifiers or protein panels. Additionally, integration of proteomics data with those from other techniques, such as genomics, transcriptomics, and metabolomics, is expected to provide more comprehensive snapshots and a deeper understanding of the mechanisms involved in the pathophysiology after solid organ transplantation.…”

Urinary biomarkers of chronic allograft nephropathy

“…Since the first successful kidney transplant in 1954, kidney transplantation has become the routine management for patients presenting with end‐stage renal disease (ESRD) . The two most common causes of long‐term graft loss remain “death with a functioning graft,” usually from a marked excess of cardiovascular mortality in allograft recipients, and chronic allograft nephropathy (CAN) , the term given to the development of fibrotic processes leading to progressive allograft dysfunction with variable proteinuria and hypertension . Despite the significant improvement in the rate of acute rejection over the last decade , CAN remains the principle cause of late graft loss after the first year post renal transplantation , accounting for 50–80% of graft losses after this time .…”