Co-administration of ezetimibe enhances proteinuria-lowering effects of pitavastatin in chronic kidney disease patients partly via a cholesterol-independent manner.
Since co-administration of ezetimibe, a specific inhibitor of cholesterol absorption into the intestine, has been shown to augment lipid-lowering effects of statins, ezetimibe plus statins is a novel therapeutic strategy for the treatment of dyslipidemia in high-risk patients. Statins have been shown to ameliorate renal function and reduce proteinuria in patients with chronic kidney disease (CKD). However, effects of co-administration of ezetimibe with statins on renal damage and dysfunction in CKD patients remain unknown. In this study, we examined whether co-administration of ezetimibe with pitavastatin could augment renoprotective properties of pitavastatin in non-diabetic CKD patients with dyslipidemia. Total cholesterol, LDL-cholesterol and triglycerides levels were reduced more by co-administration of ezetimibe (10mg/day) with pitavastatin (2mg/day) (n=10) than by pitavastatin alone (n=10). In addition, ezetimibe plus pitavastatin treatment produced significant incremental reduction in proteinuria related to pitavastatin therapy alone. In univariate analyses, proteinuria was correlated with plasma levels of total cholesterol, LDL-cholesterol, triglycerides, HDL-cholesterol (inversely), asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, and urinary excretion levels of L-fatty acid binding protein (L-FABP), a marker of tubular injury and 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker. Multiple stepwise regression analysis revealed that LDL-cholesterol (p<0.001) and urinary excretion levels of L-FABP (p=0.001) and 8-OHdG (p<0.001) were independently related to proteinuria (R(2)=0.969). Our present study demonstrated for the first time that co-administration of ezetimibe enhanced proteinuria-lowering effects of pitavastatin in non-diabetic CKD patients partly via a cholesterol-independent manner. Ezetimibe may have pleiotropic actions that could contribute to renoprotective properties of this lipid-lowering agent.
Nakamura
Tsukasa
T
Division of Nephrology, Department of Internal Medicine, Shinmatsudo Central General Hospital, Chiba, Japan.
Sato
Eiichi
E
Fujiwara
Nobuharu
N
Kawagoe
Yasuhiro
Y
Ueda
Yoshihiko
Y
Suzuki
Tsukasa
T
Ueda
Seiji
S
Fukami
Kei
K
Okuda
Seiya
S
Yamagishi
Sho-Ichi
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D001384:Azetidines / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D000069438:Ezetimibe; D050556:Fatty Acid-Binding Proteins / Q000652:urine; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D011804:Quinolines / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001384:Azetidines; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; D014280:Triglycerides; C018524:N,N-dimethylarginine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D001120:Arginine; D002784:Cholesterol; D000069438:Ezetimibe; D003849:Deoxyguanosine; C108475:pitavastatin