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  • Review Article
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Application of proteomic analysis to the study of renal diseases

Abstract

Proteomics-based approaches are generating considerable data in clinical nephrology covering almost all aspects of the discipline. Proteomic experiments commonly involve fractionation and protein separation, followed by mass spectrometric analysis to identify proteins and peptides. Biostatistical and bioinformatical input is essential in such experiments, from initial experimental design to analysis of data. Standardization of procedures is an important research objective. Depending on study design, results can lead to biomarker discovery, mechanistic insight and identification of potential avenues for therapeutic intervention and treatment evaluation. Understanding proteomic information and its place in current clinical research and practice is fundamental. This Review describes proteomic experimentation and the concepts behind it, and gives an overview of its application to important areas in clinical nephrology including acute kidney injury, chronic kidney disease, end-stage renal disease, genetic diseases and fluid and electrolyte disorders, with a particular focus on biomarker discovery. The importance of future developments, such as the establishment of an infrastructure for a 'biomarker pipeline' with structured validation pathways for candidate biomarkers and development of clinical assays, is also discussed and some future perspectives are presented.

Key Points

  • Proteomic analyses are currently being applied to almost all aspects of nephrology; this approach results in the proposition of candidate biomarkers for renal disease and provides mechanistic insight

  • Discoveries in proteomic research are generating new hypotheses and opening new potential avenues for therapeutic intervention and evaluation of the efficacy of treatment

  • Proteomic experiments commonly involve sample fractionation and protein separation, followed by mass spectrometry analysis

  • Biostatistical and bioinformatical input are critical elements in all aspects of proteomics, from initial experimental design to analysis of data

  • Focus should increase on ensuring the high quality of samples, clinical data and experimental design; standardization of research practice remains an important goal of the field

  • A 'biomarker pipeline' must be devised to harness the potential of proteomics, including validation (also known as qualification) pathways for candidate biomarkers and development of assays for use in clinical practice

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Figure 1: Overview of the main strategies employed in proteomic studies.
Figure 2: Workflow in proteomic biomarker discovery experiments.
Figure 3: Protein identification by mass spectrometry.

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Smith, M., Banks, R., Wood, S. et al. Application of proteomic analysis to the study of renal diseases. Nat Rev Nephrol 5, 701–712 (2009). https://doi.org/10.1038/nrneph.2009.183

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