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

  • 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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Author:Jialing Huang, Marcela Covic, Cornelia Huth, Martina Rommel, Jonathan Adam, Sven ZukunftORCiD, Cornelia Prehn, Li Wang, Jana Nano, Markus Scheerer, Susanne Neschen, Gabi Kastenmüller, Christian Gieger, Michael Laxy, Freimut Schliess, Jerzy Adamski, Karsten Suhre, Martin Hrabé de Angelis, Annette Peters, Rui Wang-Sattler
Parent Title (English):Metabolites
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/02/03
Date of first Publication:2021/02/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/11/03
Tag:chronic kidney disease; diabetic nephropathy; high-fat-diet; leptin receptor-deficient mouse; liver; lungs; metabolomics; prediabetes and type 2 diabetes; reduced kidney function
Issue:2, art. 89
Page Number:16
First Page:1
Last Page:16
Part of this research was supported by the 19076 and 20679 iPDM-GO “Integrated Person- alized Diabetes Management goes Europe” innovation project supported by EIT Health. EIT Health is supported by the EIT, a body of the European Union. K.S. is supported by Biomedical Research Program funds at Weill Cornell Medical College in Qatar, a program funded by the Qatar Foundation. The KORA study was initiated and financed by the Helmholtz Zentrum München—German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ.
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0