Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease

Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Molecular &amp Cellular Proteomics (Impact Factor: 7.25). 11/2010; 9(11):2424-37. DOI: 10.1074/mcp.M110.001917
Source: PubMed

ABSTRACT Because of its availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics. However, the lack of comparable data sets from large cohorts has greatly hindered the development of clinical proteomics. Here, we report the establishment of a reproducible, high resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins, ranging from 800 to 17,000 Da, using samples from 3,600 individuals analyzed by capillary electrophoresis coupled to MS. All processed data were deposited in an Structured Query Language (SQL) database. This database currently contains 5,010 relevant unique urinary peptides that serve as a pool of potential classifiers for diagnosis and monitoring of various diseases. As an example, by using this source of information, we were able to define urinary peptide biomarkers for chronic kidney diseases, allowing diagnosis of these diseases with high accuracy. Application of the chronic kidney disease-specific biomarker set to an independent test cohort in the subsequent replication phase resulted in 85.5% sensitivity and 100% specificity. These results indicate the potential usefulness of capillary electrophoresis coupled to MS for clinical applications in the analysis of naturally occurring urinary peptides.

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Available from: Petra Zürbig, Aug 25, 2015
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    • "There have been a number of studies, especially using urine, that have developed biomarkers models for a number of different diseases using capillary electrophoresis (CE) and mass spectrometry (MS). Those investigated so far range from renal disorders [16] [17] to cardiovascular disease [18] and diabetes [19]. "
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    • "The interfaces can be divided into sheathflow and sheathless designs [4]. Sheath-flow interfaces use a sheath fluid that mixes with the electrophoretic stream at the exit of the separation capillary [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]. The sheath liquid helps stabilize the electrospray, provides electrical contact with the distal end of the separation capillary, and allows dilution of the separation buffer to make it more compatible with ESI detection [14]. "
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    • "This model was subsequently validated in a blinded test set of 280 samples yielding 97.8% sensitivity and 85.5% specificity. Most of the CKD biomarker peptides were found to be fragments of collagen, uromodulin fragments, and some different blood protein fragments [11]. "
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