TY  - JOUR
A1  - Huang, Jialing
A1  - Covic, Marcela
A1  - Huth, Cornelia
A1  - Rommel, Martina
A1  - Adam, Jonathan
A1  - Zukunft, Sven
A1  - Prehn, Cornelia
A1  - Wang, Li
A1  - Nano, Jana
A1  - Scheerer, Markus
A1  - Neschen, Susanne
A1  - Kastenmüller, Gabi
A1  - Gieger, Christian
A1  - Laxy, Michael
A1  - Schliess, Freimut
A1  - Adamski, Jerzy
A1  - Suhre, Karsten
A1  - Hrabé de Angelis, Martin
A1  - Peters, Annette
A1  - Wang-Sattler, Rui
T1  - Validation of candidate phospholipid biomarkers of chronic kidney disease in hyperglycemic individuals and their organ-specific exploration in leptin receptor-deficient db/db mouse
T2  - Metabolites
N2  - 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.
KW  - chronic kidney disease
KW  - prediabetes and type 2 diabetes
KW  - diabetic nephropathy
KW  - reduced kidney function
KW  - leptin receptor-deficient mouse
KW  - high-fat-diet
KW  - liver
KW  - lungs
KW  - metabolomics
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62158
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-621582
SN  - 2218-1989
N1  - 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.
VL  - 11
IS  - 2, art. 89
SP  - 1
EP  - 16
PB  - MDPI
CY  - Basel
ER  -