Abstract

Using targeted NMR spectroscopy of 227 fasting serum metabolic traits, we searched for novel metabolic signatures of renal function in 926 type 2 diabetics (T2D) and 4838 non-diabetic individuals from four independent cohorts. We furthermore investigated longitudinal changes of metabolic measures and renal function and associations with other T2D microvascular complications. 142 traits correlated with glomerular filtration rate (eGFR) after adjusting for confounders and multiple testing: 59 in diabetics, 109 in non-diabetics with 26 overlapping. The amino acids glycine and phenylalanine and the energy metabolites citrate and glycerol were negatively associated with eGFR in all the cohorts, while alanine, valine and pyruvate depicted opposite association in diabetics (positive) and non-diabetics (negative). Moreover, in all cohorts, the triglyceride content of different lipoprotein subclasses showed a negative association with eGFR, while cholesterol, cholesterol esters (CE), and phospholipids in HDL were associated with better renal function. In contrast, phospholipids and CEs in LDL showed positive associations with eGFR only in T2D, while phospholipid content in HDL was positively associated with eGFR both cross-sectionally and longitudinally only in non-diabetics. In conclusion, we provide a wide list of kidney function–associated metabolic traits and identified novel metabolic differences between diabetic and non-diabetic kidney disease.

Details

Title
Circulating metabolic biomarkers of renal function in diabetic and non-diabetic populations
Author
Barrios, Clara 1 ; Zierer, Jonas 2   VIAFID ORCID Logo  ; Würtz, Peter 3 ; Haller, Toomas 4 ; Metspalu, Andres 4 ; Gieger, Christian 5 ; Thorand, Barbara 6 ; Meisinger, Christa 7 ; Waldenberger, Melanie 5 ; Raitakari, Olli 8 ; Lehtimäki, Terho 9 ; Otero, Sol 10 ; Rodríguez, Eva 11 ; Pedro-Botet, Juan 12 ; Kähönen, Mika 13 ; Ala-Korpela, Mika 14 ; Kastenmüller, Gabi 15 ; Spector, Tim D 16 ; Pascual, Julio 11 ; Menni, Cristina 16   VIAFID ORCID Logo 

1  Department for Twin Research, King’s College London, London, UK; Department of Nephrology, Hospital del Mar, Institut Mar d’Investigacions Mediques, Barcelona, Spain 
2  Department for Twin Research, King’s College London, London, UK; Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Weill Cornell Medical College, New York City, USA 
3  Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland; Nightingale Health Ltd, Helsinki, Finland 
4  Estonian Genome Center, University of Tartu, Tartu, Estonia 
5  Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Research Unit Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany 
6  Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany 
7  Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Chair of Epidemiology, Ludwig-Maximilians-Universität München, UNIKA-T, Augsburg, Germany 
8  Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland 
9  Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland 
10  Department of Nephrology, Hospital del Mar, Institut Mar d’Investigacions Mediques, Barcelona, Spain; Department of Nephrology, Consorci Sanitari del Garraf, Barcelona, Spain 
11  Department of Nephrology, Hospital del Mar, Institut Mar d’Investigacions Mediques, Barcelona, Spain 
12  Department of Endocrinology and Nutrition, Hospital del Mar, Institut Mar d’Investigacions Mediques, Barcelona, Spain 
13  Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland 
14  Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK; Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK; Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland; Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia 
15  Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany 
16  Department for Twin Research, King’s College London, London, UK 
Pages
1-11
Publication year
2018
Publication date
Oct 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-33507-7
ProQuest document ID
2120171400
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.