Additional renoprotective effects of azelnidipine combined with angiotensin receptor blockers in patients with diabetic nephropathy.
Azelnidipine has been reported to have antioxidant effects and attenuates tubulointerstitial ischemia. The aim of the present study was to determine whether azelnidipine exerts additional renoprotective effects to angiotensin II receptor blockers (ARBs) in hypertensive patients with diabetic nephropathy and microalbuminuria. 45 hypertensive patients with diabetes mellitus and microalbuminuria who were already being treated with ARBs were enrolled in this study. Azelnidipine was added to the drug treatment of 30 patients (8 mg/day, n = 15, or 16 mg/day, n = 15) whilst the remaining 15 control patients were not treated with azelnidipine. In all patients, urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and urinary liver-type fatty acid-binding protein (L-FABP) levels were significantly correlated (r = 0.587, p = 0.0006). However, urinary albumin excretion (UAE) was not correlated with the levels of urinary 8-OHdG (r = 0.1975, p = 0.2956) or urinary L-FABP (r = 0.2057, p = 0.2759). Azelnidipine significantly reduced UAE, urinary 8-OHdG and urinary L-FABP after 6 (p < 0.05) and 12 months (p < 0.05). Although blood pressure was comparable between the azelnidipine doses of 8 and 16 mg/day, the UAE (p < 0.05 after 12 months), urinary 8-OHdG (p < 0.05 after 6 and 12 months) and urinary L-FABP (p < 0.05 after 6 and 12 months) levels were more significantly reduced in patients receiving the higher dose of 16 mg/day. These data may suggest that the addition of azelnidipine treatment to therapy with ARBs has dose-dependent antioxidant and renoprotective effects beyond blood pressure-lowering effects in hypertensive diabetic nephropathy patients.
Nakamura
T
T
Department of Internal Medicine, Shinmatsudo Central General Hospital, Chiba, Japan.
Inoue
T
T
Fujiwara
N
N
Kawagoe
Y
Y
Sugaya
T
T
Ueda
Y
Y
Koide
H
H
Node
K
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D001383:Azetidinecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002121:Calcium Channel Blockers; D003404:Creatinine / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000652:urine; D004095:Dihydropyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D050556:Fatty Acid-Binding Proteins / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D001383:Azetidinecarboxylic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003404:Creatinine; D003849:Deoxyguanosine; C061679:azelnidipine