Proteomics and Renal Transplantation: Searching for Novel Biomarkers and Therapeutic Targets

Abstract

Renal transplantation has emerged as the preferred option for many patients with endstage renal failure. While significant progress has been achieved in short-term outcomes, long-term survival has only marginally improved. Adaptation of immunosuppressive drugs to the individual needs of every patient at every time point after transplant will be essential to improve long-term outcomes. Thus, assays are required that detect allograft injury very early, which implies frequent noninvasive measurements (e.g. in urine or serum). In this review, we describe important general aspects in urine biomarker discovery using proteomics and discuss currently published studies. Although proteomics has the potential to provide insights into complex pathophysiological processes and reveal novel diagnostic biomarkers as well as therapeutic drug targets, the actual status of urine proteomic activities in renal transplantation is still far from reaching these ambitious goals. Copyright © 2008 S. Karger AG, Basel Current Problems in Renal TransplantationAlthough short-term renal allograft survival has continuously improved over the last two decades and acute clinical rejection episodes have been significantly reduced, long-term outcome became only marginally better [1,2]. There are several possible interpretations for this contradictory finding. First, due to the growing gap between the increasing number of patients waiting for a deceased donor organ and the decreasing availability of organs with excellent quality, more marginal donors with pre-existing kidney pathologies have been used in recent years

The Clinical Significance of Early Proteinuria After Renal Transplantation

“…Intervention at this late stage has less chance of success (1). For this reason, research interest has focused on alternative strategies to diagnose early graft injury including diverse techniques such as proteomics, genomics, immunological assays and the use of protocol biopsies (2,3).…”

Characterization of acute renal allograft rejection by human serum proteomic analysis

“…2-D DIGE is an effective technology for separating complex protein samples and for quantifying protein levels between samples [8] . To our knowledge, there have been some studies about urine biomarker discovery in renal allograft rejection patients using proteomics method [9][10][11][12] . There have been few studies about serum allograft rejection biomarkers in animal transplant model [13,14] .…”

Urinary Biomarkers in Acute Kidney Transplant Dysfunction

“…Proteomics analysis relies on the extraction and separation of the protein from the human samples, fractionation of this protein into peptides by using 2D gel electrophoresis (or using the whole protein), then performing one of the techniques: matrix-assisted laser desorption ionization (MALDI) or ionizing the whole protein by surface-enhanced laser desorption ionization (SELDI) or capillary electrophoresis coupled to mass spectrometry (CE-MS) [3]. SELDI-TOF-MS combines matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) with surface retentive chromatography [4]. MALDI-TOF-MS and the related technique, SELDI-MS, provide means for analyzing a complex mixture of proteins in solution [5,6] (table 1).…”

“…All currently published data were restricted to analysis of urine using this technology, which can only assess a limited part of the proteome. The continuous developments in this field including more sensitive mass spectrometers with higher mass accuracy, differential protein expression technology, and analysis of allograft tissue parts selected by laser-capture microdissection may allow deeper understanding of changes of the proteome associated with allograft rejection and injury [4]. …”