High Dietary Protein Does Not Alter Renal Prostanoids and Other Oxylipins in Normal Mice or in Those with Inherited Kidney Disease

Abstract

ABSTRACT Background Ex vivo studies suggest that increased renal prostanoids can mediate effects of high-protein (HP) compared with low-protein (LP) diets on normal and diseased kidneys. However, a short-term HP feeding study in normal male rats failed to demonstrate higher renal prostanoids in vivo. Objectives The aim of the present study was to investigate whether long-term HP feeding alters renal prostanoids in male and female mice, with and without kidney disease. Methods Weanling normal mice (CD1) and mice with kidney disease (CD1-pcy/pcy mice) were fed standard diets with normal protein [NP, 20% of energy (%E)] or HP (35%E) for 13 wk. Renal disease was assessed by histomorphometric analysis of cysts and fibrosis, and measurement of serum urea nitrogen (SUN) and creatinine concentrations. Targeted analysis of renal oxylipins was performed by HPLC-MS/MS. Results The HP diet increased kidney size and water content of normal kidneys, and worsened disease in CD1-pcy/pcy mice as indicated by higher (P < 0.05) kidney weights (8–31%), water content (8–10%), cyst volume (36–60%), fibrous volume (44–53%), and SUN (47–55%). Diseased compared with normal kidneys had higher (P < 0.05) concentrations of 6 of 11 prostanoids and lower (P < 0.05) concentrations of 33 of 54 other oxylipins. This is consistent with previously known effects of dietary HP and disease effects on the kidney. However, the HP diet did not alter renal prostanoids and other renal oxylipins in either normal or diseased kidneys (P < 0.05), despite having the expected physiological effects on normal and diseased kidneys. This study also showed that females have higher concentrations of renal prostanoids [9 of 11 prostanoids higher (P < 0.05) in females], but lower concentrations of other oxylipins [28 of 54 other oxylipins lower (P < 0.05) in females]. Conclusions The effects of HP diets on normal and diseased kidneys in CD1 and CD1-pcy/pcy mice are independent of renal oxylipin alterations.