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  • Review Article
  • Published:

Proteomic biomarkers in kidney disease: issues in development and implementation

Nature Reviews Nephrology volume 11, pages 221–232 (2015)Cite this article

Subjects

Key Points

  • A useful clinical biomarker must have an exact and well-defined context of use, generally linked to a therapeutic consequence, and every new biomarker identified must be validated in independent studies

  • Proteomic studies have detected initial sets of biomarkers that have demonstrated potential in the context of kidney disease, but they have not yet been fully integrated into clinical use

  • High-dimensional classifiers based on multiple, well-defined biomarkers generally outperform individual markers, because such classifiers account for disease complexity and molecular heterogeneity

  • Guidance from professional, clinical and scientific societies on the clinical use of biomarkers and their development would substantially improve clinical biomarker research

  • The lack of appropriate samples in sufficient numbers is a major barrier to the further development of effective proteomic biomarkers; publicly funded biobanks could substantially improve this situation

  • Evaluation of proteomics data employing systems biology approaches has the potential to yield information that cannot be established using proteomics alone

Abstract

Proteomic biomarkers offer the hope of improving the management of patients with kidney diseases by enabling more accurate and earlier detection of renal pathology than is possible with currently available biomarkers, serum creatinine and urinary albumin. In addition, proteomic biomarkers could also be useful to define the most suitable therapeutic targets in a given patient or disease setting. This Review describes the current status of proteomic and protein biomarkers in the context of kidney diseases. The valuable lessons learned from early clinical studies of potential proteomic biomarkers in kidney disease are presented to give context to the newly identified biomarkers, which have potential for actual clinical implementation. This article also includes an overview of protein-based biomarker candidates that are undergoing development for use in nephrology, focusing on those with the greatest potential for clinical implementation. Relevant issues and problems associated with the discovery, validation and clinical application of proteomic biomarkers are discussed, along with suggestions for solutions that might help to guide the design of future proteomic studies. These improvements might remove some of the current obstacles to the utilization of proteomic biomarkers, with potentially beneficial results.

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Figure 1: Research interest in biomarkers of kidney disease.
Figure 2: The two main routes of proteomic biomarker development.

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Acknowledgements

The authors' research is supported in part by the European Commission Seventh Framework Programme (FP7) projects Clinical and System–Omics for Identification of the Molecular Determinants of Established Chronic Kidney Disease (iMODE-CKD, PEOPLE-ITN-GA-2013-608332), Markers for Sub-Clinical Cardiovascular Risk Assessment (EU-MASCARA, HEALTH-2011 278,249), Systems Biology to Identify Molecular Targets for Vascular Disease Treatment (SysVasc, HEALTH-2013 603288) and Systems Biology: Towards Novel Chronic Kidney Disease Diagnosis and Treatment (SysKID HEALTH–F2–2009–241544). The authors are grateful to Gert Mayer, University of Innsbruck, Austria, and Claudia Pontillo, Mosaiques Diagnostics, Germany, for critically reviewing the manuscript and to Clemens Gutzeit for help with preparing the original artwork.

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Authors and Affiliations

  1. Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK

    Harald Mischak & Christian Delles

  2. Division of Biotechnology, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4, Athens, 11527, Greece

    Antonia Vlahou

  3. Department of Nephrology, Department of Internal Medicine, Ghent University Hospital, University Hospital Gent, De Pintelaan 185, Ghent, B9000, Belgium

    Raymond Vanholder

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  1. Harald Mischak
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  2. Christian Delles
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  4. Raymond Vanholder
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All authors contributed equally to writing this article, researching the data, reviewing and/or editing of the manuscript before submission, and discussion of its content.

Corresponding author

Correspondence to Raymond Vanholder.

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Competing interests

H.M. is the co-founder and co-owner of Mosaiques Diagnostics and DiaPat—companies that provide clinical proteomics services—and developed the CKD273 urinary proteomic classifier. The other authors declare no competing interests.

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Mischak, H., Delles, C., Vlahou, A. et al. Proteomic biomarkers in kidney disease: issues in development and implementation. Nat Rev Nephrol 11, 221–232 (2015). https://doi.org/10.1038/nrneph.2014.247

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