Adenine-Induced Nephropathy Reduces Atherosclerosis in Knockout Mice.

Background: Cardiovascular events are the main cause of death in patients with chronic kidney disease. We hypothesize that the protective effects of renal cholesterol and vitamin D metabolism are lost under this condition. Nephropathy was induced by adenine in Apolipoprotein E knockout mice. The atherosclerotic phenotype was compared to mice with normal renal function.

Methods: Mice were fed a western diet ±0.15% adenine. Urine and feces were collected to assess renal function and fecal output. Atherosclerosis, serum lipoprotein composition and functionality, hepatic lipids, and expression of genes involved in lipid metabolism, vitamin D and Na homeostasis, were assessed. Bones were analyzed by microCT.

Results: Mice fed with adenine showed enhanced urinary Na, Ca, and Pi excretion, reduced urinary pH, Urea/Urea, and Creatinine/Creatinine ratios. They developed less atherosclerosis. Lipoproteins in serum and hepatic lipids remained unchanged. Cholesterol efflux increased. Fecal output of cholesteryl ester and triglycerides increased. In the liver, mRNA levels of , , and increased; in the kidneys, , , and decreased. Adenine increased cholesterol efflux in vitro. Tibias were shorter.

Conclusion: Adenine induced tubular damage and was athero-protective because of enhanced cholesterol efflux and lipids elimination in feces. Bone growth was also affected.