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Metabolomics in the study of kidney diseases

Nature Reviews Nephrology volume 8, pages 22–33 (2012)Cite this article

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Abstract

Metabolomics—the nontargeted measurement of all metabolites produced by the body—is beginning to show promise in both biomarker discovery and, in the form of pharmacometabolomics, in aiding the choice of therapy for patients with specific diseases. In its two basic forms (pattern recognition and metabolite identification), this developing field has been used to discover potential biomarkers in several renal diseases, including acute kidney injury (attributable to a variety of causes), autosomal dominant polycystic kidney disease and kidney cancer. NMR and gas chromatography or liquid chromatography, together with mass spectrometry, are generally used to separate and identify metabolites. Many hurdles need to be overcome in this field, such as achieving consistency in collection of biofluid samples, controlling for batch effects during the analysis and applying the most appropriate statistical analysis to extract the maximum amount of biological information from the data obtained. Pathway and network analyses have both been applied to metabolomic analysis, which vastly extends its clinical relevance and effects. In addition, pharmacometabolomics analyses, in which a metabolomic signature can be associated with a given therapeutic effect, are beginning to appear in the literature, which will lead to personalized therapies. Thus, metabolomics holds promise for early diagnosis, increased choice of therapy and the identification of new metabolic pathways that could potentially be targeted in kidney disease.

Key Points

  • Metabolomics is the study of all small-molecule metabolites produced by the body and thus provides a functional fingerprint of the physiological and pathophysiological state of the body

  • Two useful clinical methods exist for metabolomics analysis: pattern recognition and metabolite identification

  • The study design (adequate sample size and the statistical analysis strategy) should be carefully planned to detect small differences in metabolic profiles in a population with wide biological variation

  • Metabolomics has resulted in potential biomarkers for several renal diseases, but to become true biomarkers, the clinical merit of potential biomarkers needs to be validated in separate targeted studies

  • Pharmacometabolomics could enable metabolomics to be used in personalized medicine

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Figure 1: The science of metabolomics has been practiced in the field of nephrology, albeit with slightly less sophisticated analytical techniques, for centuries.
Figure 2: This flow chart details the use of metabolomics to find clinically useful biomarkers.
Figure 3: Two separate methods exist for metabolomics analysis that can stratify patients as being healthy or having a disease: global metabolomics refers to true biomarker discovery and chemical identification, whereas metabolic fingerprinting refers to pattern recognition to segregate healthy patients from patients with a disease without the need for rigorous chemical identification or quantification of metabolites.
Figure 4: Pharmacometabolomics combines metabolomic analysis with drug response through the association of altered metabolites with metabolic pathways that are affected by specific drugs.

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Acknowledgements

R. H. Weiss would like to acknowledge the support of NIH grants 5UO1CA86402 (Early Detection Research Network), 1R01CA135401-01A1 and 1R01DK082690-01A1, and the Medical Service of the US Department of Veterans' Affairs.

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Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Genome and Biomedical Sciences Building, Room 6312

    Robert H. Weiss

  2. University of California, Davis, 95616, CA, USA

    Robert H. Weiss

  3. Division of Biostatistics, Medical Sciences 1-C, University of California, Davis, 95616, CA, USA

    Kyoungmi Kim

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Weiss, R., Kim, K. Metabolomics in the study of kidney diseases. Nat Rev Nephrol 8, 22–33 (2012). https://doi.org/10.1038/nrneph.2011.152

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