TY - JOUR
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
AU - Huang, Jialing
AU - Covic, Marcela
AU - Huth, Cornelia
AU - Rommel, Martina
AU - Adam, Jonathan
AU - Zukunft, Sven
AU - Prehn, Cornelia
AU - Wang, Li
AU - Nano, Jana
AU - Scheerer, Markus F.
AU - Neschen, Susanne
AU - Kastenmüller, Gabi
AU - Gieger, Christian
AU - Laxy, Michael
AU - Schliess, Freimut
AU - Adamski, Jerzy
AU - Suhre, Karsten
AU - De Angelis, Martin Hrabe
AU - Peters, Annette
AU - Wang-Sattler, Rui
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/1
Y1 - 2021/1
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.
AB - 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 - Diabetic nephropathy
KW - High-fat-diet
KW - Leptin receptor-deficient mouse
KW - Liver
KW - Lungs
KW - Metabolomics
KW - Prediabetes and type 2 diabetes
KW - Reduced kidney function
UR - http://www.scopus.com/inward/record.url?scp=85100747468&partnerID=8YFLogxK
U2 - 10.3390/metabo11020089
DO - 10.3390/metabo11020089
M3 - Article
AN - SCOPUS:85100747468
SN - 2218-1989
VL - 11
SP - 1
EP - 16
JO - Metabolites
JF - Metabolites
IS - 2
M1 - 89
ER -
