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A proton nuclear magnetic resonance-based metabolomic approach in IgA nephropathy urinary profiles

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Abstract

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. Both one-dimensional NOESY and transverse-relaxation filter CPMG NMR spectra were recorded to investigate the urine metabolome of 24 IgAN patients and to detect altered metabolic profiles in comparison with 68 healthy matched controls. The spectral data were analyzed using multivariate statistical techniques. The analysis revealed that the NMR spectra of IgAN patients were statistically different from those of the controls (P = 4 × 10−7 for 1D-NOESY and P = 2 × 10−7 for CPMG). The robustness of the determined statistical model was confirmed by its predictive performance (for the 1D-NOESY dataset: sensitivity = 67 %, specificity = 95 %; for the CPMG dataset sensitivity = 60 %, specificity = 94 %). For the first time we found metabolites, including betaine and citrate, that are differentially modulated in IgAN patients compared to controls and that may be directly involved in the pathogenesis of IgAN. These metabolites may influence, directly or indirectly, the TNF-α, a regulating factor of the Th1/Th2 cell balance that is relevant in the pathology. The involvement of metabolites such as betaine and citrate in TNF-α regulation supports the power of the identified metabolic profiles to discern IgAN from controls.

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Abbreviations

CA:

Canonical analysis

CPMG:

Carr–Purcell–Meiboom–Gill spin-echo sequence

IgAN:

IgA nephropathy

IPA:

Ingenuity pathway analysis

MANOVA:

Multivariate analysis of variance

NMR:

Nuclear magnetic resonance

NOESY:

Nuclear overhauser effect spectroscopy

PC:

Principal component

PCA:

Principal component analysis

TNF-α:

Tumor necrosis factor alpha

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Acknowledgments

We are grateful to the patients for their cooperation in this study. This work was supported by Regione Puglia (Grant BISIMANE Project 44/2008) and Ministero dell'Istruzione, dell'Università e della Ricerca (Grant FIRB CAROMIX RBAP11B2SX_008). Maintenance of the NMR spectrometer was funded in part by the Department of Biotechnology of the University of Verona.

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Authors and Affiliations

  1. C.A.R.S.O. Consortium, Strada Provinciale Casamassima Km 3, 70010, Valenzano, Bari, Italy

    Laura Del Coco, Fabio Sallustio, Francesco P. Fanizzi & Francesco P. Schena

  2. Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134, Verona, Italy

    Michael Assfalg & Mariapina D’Onofrio

  3. Nephrology Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Policlinico, Piazza G. Cesare 11, 70124, Bari, Italy

    Fabio Sallustio, Francesco Pesce & Francesco P. Schena

  4. Department of Science, Biological and Environmental Sciences and Technologies, University of Salento, Prov.le Lecce-Monteroni, 73100, Lecce, Italy

    Laura Del Coco, Fabio Sallustio & Francesco P. Fanizzi

  5. Clinical Cardiology and Imaging, National Heart & Lung Institute, Imperial College London, Room 2058, Royal Brompton Hospital, Sydney Street, SW3 6NP, London, UK

    Francesco Pesce

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  1. Laura Del Coco
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  2. Michael Assfalg
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  7. Francesco P. Schena
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Correspondence to Michael Assfalg or Francesco P. Schena.

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Del Coco, L., Assfalg, M., D’Onofrio, M. et al. A proton nuclear magnetic resonance-based metabolomic approach in IgA nephropathy urinary profiles. Metabolomics 9, 740–751 (2013). https://doi.org/10.1007/s11306-012-0489-2

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  • DOI: https://doi.org/10.1007/s11306-012-0489-2

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