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Huang, J. ; Huth, C. ; Covic, M. ; Troll, M. ; Adam, J. ; Zukunft, S. ; Prehn, C. ; Wang, L. ; Nano, J. ; Scheerer, M.F. ; Neschen, S. ; Kastenmüller, G. ; Suhre, K.* ; Laxy, M. ; Schliess, F.* ; Gieger, C. ; Adamski, J. ; Hrabě de Angelis, M. ; Peters, A. ; Wang-Sattler, R.

Machine learning approaches reveal metabolic signatures of incident chronic kidney disease in individuals with prediabetes and type 2 diabetes.

Diabetes 69, 2756-2765 (2020)

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Early and precise identification of individuals with pre-diabetes and type 2 diabetes (T2D) at risk for progressing to chronic kidney disease (CKD) is essential to prevent complications of diabetes. Here, we identify and evaluate prospective metabolite biomarkers and the best set of predictors of CKD in the longitudinal, population-based Cooperative Health Research in the Region of Augsburg (KORA) cohort by targeted metabolomics and machine learning approaches. Out of 125 targeted metabolites, sphingomyelin C18:1 and phosphatidylcholine diacyl C38:0 were identified as candidate metabolite biomarkers of incident CKD specifically in hyperglycemic individuals followed during 6.5 years. Sets of predictors for incident CKD developed from 125 metabolites and 14 clinical variables showed highly stable performances in all three machine learning approaches and outperformed the currently established clinical algorithm for CKD. The two metabolites in combination with five clinical variables were identified as the best set of predictors, and their predictive performance yielded a mean area value under the receiver operating characteristic curve of 0.857. The inclusion of metabolite variables in the clinical prediction of future CKD may thus improve the risk prediction in people with prediabetes and T2D. The metabolite link with hyperglycemia-related early kidney dysfunction warrants further investigation.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Risk; Sphingomyelin; Prediction; Albuminuria; Progression; Population; Children

ISSN (print) / ISBN 0012-1797

e-ISSN 1939-327X

Journal Diabetes

Quellenangaben Volume: 69, Issue: 12, Pages: 2756-2765

Publisher American Diabetes Association

Publishing Place Alexandria, VA.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)
Institute of Experimental Genetics (IEG)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Bioinformatics and Systems Biology (IBIS)
Institute of Health Economics and Health Care Management (IGM)

Grants Biomedical Research Program funds at Weill Cornell Medicine -Qatar, a program - Qatar Foundation
EIT, a body of the European Union
European Institute of Innovation and Technology (EIT) Health
European Union Seventh Framework Programme (EU FP7)
Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universitat, as part of LMUinnovativ
State of Bavaria
Helmholtz Zentrum Munchen -German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF)