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1,5-Anhydroglucitol predicts CKD progression in macroalbuminuric diabetic kidney disease: results from non-targeted metabolomics

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Abstract

Introduction

Metabolomics allows exploration of novel biomarkers and provides insights on metabolic pathways associated with disease. To date, metabolomics studies on CKD have been largely limited to Caucasian populations and have mostly examined surrogate end points.

Objective

In this study, we evaluated the role of metabolites in predicting a primary outcome defined as dialysis need, doubling of serum creatinine or death in Brazilian macroalbuminuric DKD patients.

Methods

Non-targeted metabolomics was performed on plasma from 56 DKD patients. Technical triplicates were done. Metabolites were identified using Agilent Fiehn GC/MS Metabolomics and NIST libraries (Agilent MassHunter Work-station Quantitative Analysis, version B.06.00). After data cleaning, 186 metabolites were left for analyses.

Results

During a median follow-up time of 2.5 years, the PO occurred in 17 patients (30.3%). In non-parametric testing, 13 metabolites were associated with the PO. In univariate Cox regression, only 1,5-anhydroglucitol (HR 0.10; 95% CI 0.01–0.63, p = .01), norvaline and l-aspartic acid were associated with the PO. After adjustment for baseline renal function, 1,5-anhydroglucitol (HR 0.10; 95% CI 0.02–0.63, p = .01), norvaline (HR 0.01; 95% CI 0.001–0.4, p = .01) and aspartic acid (HR 0.12; 95% CI 0.02–0.64, p = .01) remained significantly and inversely associated with the PO.

Conclusion

Our results show that lower levels of 1,5-anhydroglucitol, norvaline and l-aspartic acid are associated with progression of macroalbuminuric DKD. While norvaline and l-aspartic acid point to interesting metabolic pathways, 1,5-anhydroglucitol is of particular interest since it has been previously shown to be associated with incident CKD. This inverse biomarker of hyperglycemia should be further explored as a new tool in DKD.

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Funding

FAPESP, Sao Paulo, Brazil.

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Authors and Affiliations

  1. Nephrology Division, University of São Paulo Medical School, Av Dr Enéas de Carvalho Aguiar, 255, São Paulo, SP, 05403-000, Brazil

    Gesiane Tavares, Roberto Zatz & Silvia M. O. Titan

  2. Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, São Paulo, SP, Brazil

    Gabriela Venturini, Kallyandra Padilha & Alexandre C. Pereira

  3. Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    Ravi I. Thadhani & Eugene P. Rhee

  4. Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Ravi I. Thadhani

  5. Division of Endocrinology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    Eugene P. Rhee

Authors
  1. Gesiane Tavares
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  2. Gabriela Venturini
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  3. Kallyandra Padilha
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  4. Roberto Zatz
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  5. Alexandre C. Pereira
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  6. Ravi I. Thadhani
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  7. Eugene P. Rhee
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  8. Silvia M. O. Titan
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Correspondence to Gesiane Tavares.

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Conflict of interest

Ravi I. Thadhani is a consultant to Fresenius Medical Care North America. Gesiane Tavares, Gabriela Venturini, Kallyandra Padilha, Roberto Zatz, Alexandre C. Pereira, Eugene P. Rhee, Silvia M. O. Titan declares that they have no conflict of interest.

Ethical approval

The protocol was approved by the local Ethics Committees: the Universitary Hospital Ethics Committee (CEP-HU, Sao Paulo University) and the Ethics Committee for Analysis of Research Projects (CAPPesq, Hospital das Clínicas, Sao Paulo University).

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Written informed consent was obtained from all participants and all research was performed in accordance with the 2013 Helsinki Declaration principles.

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Tavares, G., Venturini, G., Padilha, K. et al. 1,5-Anhydroglucitol predicts CKD progression in macroalbuminuric diabetic kidney disease: results from non-targeted metabolomics. Metabolomics 14, 39 (2018). https://doi.org/10.1007/s11306-018-1337-9

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