Chronic Kidney Disease Alters Vitamin A Homeostasis via Effects on Hepatic RBP4 Protein Expression and Metabolic Enzymes.
Vitamin A, via retinoic acid (RA), is a critical micronutrient. Normally, plasma concentrations are tightly regulated. Concentrations of vitamin A metabolites (13cis-RA, atRA) and relationships between RBP4 and retinoids have never been fully evaluated in adult patients with CKD. We measured retinoid and RBP4 concentrations in plasma and urine from 55 adult patients with CKD and 21 matched healthy subjects. RBP4 and retinol levels were increased approximately twofold in patients with CKD, with a negative correlation between plasma retinol and eGFR (p = 0.006) and plasma RBP4 and eGFR (p = 0.0007). RBP4 renal clearance was higher in patients with CKD than healthy subjects but not associated with eGFR. Circulating concentrations of atRA increased and concentrations of 13cis-RA decreased in subjects with CKD with no change in RA-to-retinol ratio. Increases in circulating retinol, RBP4, and atRA may be due to increased hepatic RBP4 synthesis, retinyl ester hydrolysis, and/or hepatic secretion of RBP4-retinol.
Department of Pharmaceutics, University of Washington School of Pharmacy, Seattle, Washington, USA.
J
J
Jing
Department of Pharmaceutics, University of Washington School of Pharmacy, Seattle, Washington, USA.
N
N
Isoherranen
Division of Nephrology, Department of Medicine, Kidney Research Institute, Seattle, Washington, USA.
C
C
Robinson-Cohen
Department of Pharmacy, University of Washington School of Pharmacy, Seattle, Washington, USA.
I
I
Petrie
Division of Nephrology, Department of Medicine, Kidney Research Institute, Seattle, Washington, USA.
B R
BR
Kestenbaum
Division of Nephrology, Department of Medicine, Kidney Research Institute, Seattle, Washington, USA.|Department of Pharmacy, University of Washington School of Pharmacy, Seattle, Washington, USA.
C K
CK
Yeung
D003710:Demography; D005260:Female; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011228:Prealbumin / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000378:metabolism*; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism*; D014801:Vitamin A / Q000097:blood*
D011228:Prealbumin; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D014801:Vitamin A