title: Atorvastatin reduces proteinuria in non-diabetic chronic kidney disease patients partly via lowering serum levels of advanced glycation end products (AGEs).
abstract: There is accumulating evidence that advanced glycation end products (AGEs) play a role in the development and progression of chronic kidney disease (CKD). We have previously found that atorvastatin treatment significantly reduces serum levels of AGEs in type 2 diabetic patients and subjects with non-alcoholic steatohepatitis in a cholesterol lowering-independent manner. In this study, we examined whether atorvastatin could reduce proteinuria partly via reduction of serum levels of AGEs in non-diabetic CKD patients. Ten non-diabetic normotensive stage I or II CKD patients with dyslipidemia were enrolled. Patients were treated with atorvastatin (10 mg/day) for 1 year. All subjects underwent determination of blood chemistries, proteinuria and serum levels of AGEs at baseline and after 1 year. Atorvastatin treatment for 1 year significantly decreased circulating levels of total cholesterol, LDL-cholesterol, triglycerides, and AGEs, while it increased HDL-cholesterol levels. Further, although atorvastatin treatment did not affect estimated glomerular filtration rate, it significantly reduced proteinuria. In univariate analyses, proteinuria levels were correlated with total cholesterol, LDL-cholesterol, triglycerides, HDL-cholesterol (inversely) and AGEs. Multiple stepwise regression analysis revealed that AGE level was a sole independent correlate of proteinuria. In this initial examination of the patients in this study, our present study suggests that atorvastatin could decrease proteinuria in non-diabetic CKD patients with dyslipidemia partly via reduction of serum levels of AGEs. Atorvastatin may have AGE-lowering effects in CKD patients as well that could contribute to renoprotective properties of this agent.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Shinmatsudo Central General Hospital, Chiba, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Nakamura
authors.forename: Eiichi
authors.initials: E
authors.lastname: Sato
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Fujiwara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawagoe
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Sayaka
authors.initials: S
authors.lastname: Maeda
authors.forename: Sho-ichi
authors.initials: S
authors.lastname: Yamagishi
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D011507:Proteinuria / Q000188:drug therapy*; D011758:Pyrroles / Q000627:therapeutic use*; D012720:Severity of Illness Index; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017127:Glycation End Products, Advanced; D006538:Heptanoic Acids; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin