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

Validation of candidate phospholipid biomarkers of chronic kidney disease in hyperglycemic individuals and their organ-specific exploration in leptin receptor-deficient db/db mouse.

Metabolites 11:89 (2021)

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	Open Access Gold

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Biological exploration of early biomarkers for chronic kidney disease (CKD) in (pre)diabetic individuals is crucial for personalized management of diabetes. Here, we evaluated two candidate biomarkers of incident CKD (sphingomyelin (SM) C18:1 and phosphatidylcholine diacyl (PC aa) C38:0) concerning kidney function in hyperglycemic participants of the Cooperative Health Research in the Region of Augsburg (KORA) cohort, and in two biofluids and six organs of leptin receptor-deficient (db/db) mice and wild type controls. Higher serum concentrations of SM C18:1 and PC aa C38:0 in hyperglycemic individuals were found to be associated with lower estimated glomerular filtration rate (eGFR) and higher odds of CKD. In db/db mice, both metabolites had a significantly lower concentration in urine and adipose tissue, but higher in the lungs. Additionally, db/db mice had significantly higher SM C18:1 levels in plasma and liver, and PC aa C38:0 in adrenal glands. This cross-sectional human study confirms that SM C18:1 and PC aa C38:0 associate with kidney dysfunction in pre(diabetic) individuals, and the animal study suggests a potential implication of liver, lungs, adrenal glands, and visceral fat in their systemic regulation. Our results support further validation of the two phospholipids as early biomarkers of renal disease in patients with (pre)diabetes.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Chronic Kidney Disease ; Diabetic Nephropathy ; High-fat-diet ; Leptin Receptor-deficient Mouse ; Liver ; Lungs ; Metabolomics ; Prediabetes And Type 2 Diabetes ; Reduced Kidney Function

ISSN (print) / ISBN 2218-1989

e-ISSN 2218-1989

Journal Metabolites

Quellenangaben Volume: 11, Issue: 2, Article Number: 89

Publisher MDPI

Publishing Place St Alban-anlage 66, Ch-4052 Basel, Switzerland

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Experimental Genetics (IEG)
Institute of Computational Biology (ICB)
Institute of Health Economics and Health Care Management (IGM)
CF Metabolomics & Proteomics (CF-MPC)

Grants 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)
Biomedical Research Program funds at Weill Cornell Medical College in Qatar - Qatar Foundation
EIT, a body of the European Union
EIT Health
iPDM-GO "Integrated Personalized Diabetes Management goes Europe" innovation project