Characterization of Urinary Peptide Biomarkers of Acute Rejection in Renal Allografts

O’Riordan, Edmond; Orlova, Tetiana; Podust, Vladimir N.; Chander, Praveen N.; Yanagi, Shigehisa; Nakazato, Masamitsu; Hu, Ran; Butt, Khalid M. H.; Delaney, Veronica; Goligorsky, Michael S.

doi:10.1111/j.1600-6143.2007.01733.x

Cited by 79 publications

(59 citation statements)

References 30 publications

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“…Screening studies using mass spectrometry have identified biomarkers predictive of acute allograft rejection, but for the most part these biomarkers are protein peak clusters that remain unidentified (as in Figure 2). [35][36][37][38]50,51 Two studies have now reported the identification of biomarkers after initial urine screening (Table 2). 35,50 The use of these urine biomarkers for noninvasive monitoring of renal allografts remains a little way off; however, work is now under way to examine their utility, along with that of other urine biomarkers of tubular injury, in assessing renal allograft function.…”

Section: Renal Transplantationmentioning

confidence: 99%

Urine proteomics: the present and future of measuring urinary protein components in disease

Barratt

Topham²

2007

Canadian Medical Association Journal

190

126

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P roteomics is the study of protein expression in a tissue or biological fluid. Comparison of protein patterns in biological fluids between healthy individuals and patients with disease is increasingly being used both to discover biological markers of disease (biomarkers) and to identify biochemical processes important in disease pathogenesis. Although currently available tests for urine proteins measure either the total level of urine protein or the presence of a single protein species, emerging proteomic technologies allow simultaneous examination of the patterns of multiple urinary proteins and their correlation with individual diagnoses, response to treatment or prognosis. Analysis of the various protein constituents of urine may suggest novel, noninvasive diagnostic tests, therapeutic guidance, and prognostic information for patients and clinicians.In this review, we describe the current practice of urine protein testing and the emerging technologies that are being used for analysis of the urinary proteome. BackgroundNormally, the low-molecular-weight proteins and albumin that are filtered from plasma into the early tubular fluid are almost completely reabsorbed and catabolized in the proximal tubules. As a result, daily urinary protein excretion is less than 150 mg/day, of which about 10 mg is albumin. In patients with physiologic proteinuria, the proteins excreted include mucoproteins (mainly Tamm-Horsfall protein), blood-group proteins, albumin, immunoglobulins, mucopolysaccharides and very small amounts of hormones and enzymes. Historically, proteinuria of more than 150 mg/day was regarded as abnormal. However, it is now appreciated that early renal disease is often characterized by low-level albuminuria (between 30 and 300 mg/day).1 This condition is termed microalbuminuria because the concentration of albumin is below the detection limit of traditional assays. Protein or albumin excretion greater than 300 mg/day represents overt proteinuria or macroalbuminuria; at this level, the result of standard urine dipstick testing becomes positive.Pathological proteinuria can be divided into 3 categories: glomerular proteinuria, tubular proteinuria and overload proteinuria.2 Glomerular proteinuria results from an increase in the permeability of the glomerular capillary wall to macromolecules (particularly albumin) and usually results from glomerular disease. Tubular proteinuria results from reduced reabsorption of proteins that are normally present in the glomerular filtrate or from excretion of proteins derived from injured tubular epithelial cells. It is usually caused by diseases of the tubulointerstitium. Overload proteinuria is due to an excess of low-molecular-weight proteins that are normally reabsorbed by the proximal tubules. These proteins are most often immunoglobulin light chains (in the plasma cell dyscrasias), although lysozyme (in myelomonocytic leukemia), myoglobin (in rhabdomyolysis) or hemoglobin (in intravascular hemolysis) may also be identified.Under normal conditions, urinary proteins exis...

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Section: Renal Transplantationmentioning

confidence: 99%

Urine proteomics: the present and future of measuring urinary protein components in disease

Barratt

Topham²

2007

Canadian Medical Association Journal

190

126

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“…SELDI-MS profiling indicated that there were predominantly small urine peptides or proteins (2.0-25.7 kDa) that could distinguish between renal transplant patients with no rejection and those with acute rejection [300][301][302][303][304]. Patients with acute tubulointerstitial rejection also expressed higher levels of cleaved beta-2-microglobulin (B2MG) in urine [305].…”

Section: Application To Human Disease Detectionmentioning

confidence: 99%

Human body fluid proteome analysis

2006

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The focus of this article is to review the recent advances in proteome analysis of human body fluids, including plasma/serum, urine, cerebrospinal fluid, saliva, bronchoalveolar lavage fluid, synovial fluid, nipple aspirate fluid, tear fluid, and amniotic fluid, as well as its applications to human disease biomarker discovery. We aim to summarize the proteomics technologies currently used for global identification and quantification of body fluid proteins, and elaborate the putative biomarkers discovered for a variety of human diseases through human body fluid proteome (HBFP) analysis. Some critical concerns and perspectives in this emerging field are also discussed. With the advances made in proteomics technologies, the impact of HBFP analysis in the search for clinically relevant disease biomarkers would be realized in the future.

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“…As intact ␤ 2 -microglobulin is a wellknown biomarker for tubular injury, it became obvious that cleaved ␤ 2 -microglobulin was unlikely to be specific for rejection but rather an indicator of tubular injury [27]. O'Riordan et al [26] identified ␤-defensin-1 and a fragment of ␣ 1 -antichymotrypsin as their previously detected biomarkers for renal allograft rejection, which are both involved in inflammatory processes. The other three groups have not yet identified their potential biomarkers (table 1) [13,16,17].…”

Section: Published Studies Using Proteomics In Human Transplantationmentioning

confidence: 99%

“…Interestingly, each group found a different set of urinary proteins that are associated with the investigated process. To understand these apparent discrepancies, one must consider that in each study disease definition, sample collection, [15,26] found that decreasing levels of urinary ␤-defensin-1 and increasing levels of a fragment of ␣ 1 -antichymotrypsin were associated with renal allograft rejection. Although we identified a different protein as a potential biomarker for renal allograft rejection (i.e.…”

Section: General Aspectsmentioning

confidence: 99%

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

Schaub¹,

Wilkins²,

Nickerson³

2008

Proteomics in Nephrology - Towards Clinical Applications

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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

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Characterization of Urinary Peptide Biomarkers of Acute Rejection in Renal Allografts

Cited by 79 publications

References 30 publications

Urine proteomics: the present and future of measuring urinary protein components in disease

Urine proteomics: the present and future of measuring urinary protein components in disease

Human body fluid proteome analysis

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

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