Urinary peptidomics in kidney disease and drug research

ABSTRACT

Introduction: Due to its close connection with the renal system, urine is considered a valuable source of information in kidney disease research. Peptidomics methods focus on the discovery of endogenous peptides, given their wide range of biological functions and diagnostic and therapeutic potential. Representing a non-invasive and sensitive method, technological prospects of urinary peptidomics should be evaluated in the context of drug discovery and research.

Areas covered: This review describes urinary peptidomics with focus on its application in drug research in the field of kidney diseases. The authors provide an overview of current achievements and potential future applications.

Expert opinion: The urinary peptidome is a dynamically changing source of information, able to reflect sudden and long-term changes affecting the renal system. Studies utilizing urinary peptidomics techniques have demonstrated their value in patient stratification and detection of early pathological changes in kidney disease. Serving as a liquid biopsy, urinary peptides are an invaluable tool for drug response monitoring. Nevertheless, peptidomics is largely underexplored in drug research in general, as evidenced by the scarce number of scientific publications on this topic. Further progress will be driven by the successful validation of current discoveries and continued efforts to improve the translation of results into therapeutic applications.

KEYWORDS:

• Biomarker
• clinical proteomics
• drug discovery
• kidney disease
• peptidomics
• urine

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Article highlights

• Urine represents an excellent sample material for investigation in kidney disease research, due to its stability, accessibility and close relation to renal system

• Peptides are excreted by kidneys under physiological conditions, therefore changes in their urinary content can be reflective of early molecular changes in the kidney

• Peptidomics techniques provide a highly sensitive readout, therefore are able to detect subtle change in the peptide content

• Urine, specifically urine peptides, are reflective of kidney (patho)physiology. While not serving as direct therapeutic targets, urine peptides hold substantial indirect information on molecular changes associated with kidney diseases

• CE-MS technique has matured noticeably over the past several years through methodological and technological advancements and its reproducibility has been confirmed by several investigators

• Successful application of urinary peptide panels for kidney disease diagnosis, prognosis and treatment response proves their raising utility and impact in the field of drug research

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Declaration of interest

H Mischak is founder and co-owner of Mosaiques Diagnostics while M Krochmal is an employee of Mosaiques Diagnostics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The work was supported in part by the FP7 programs ‘Clinical and system–omics for the identification of the Molecular Determinants of established Chronic Kidney Disease’ [iMODE-CKD, PEOPLE-ITN-GA-2013-608332], and “Molecular Medicine and ‘Systems Biology to Identify Molecular Targets for Vascular Disease Treatment’ [SysVasc, HEALTH-2013 603288].