title: Additive renoprotective effects of aliskiren on angiotensin receptor blocker and calcium channel blocker treatments for type 2 diabetic patients with albuminuria.
abstract: This open-label, randomized, parallel-controlled study investigated the effects of the direct renin inhibitor aliskiren on 64 hypertensive type 2 diabetic patients with chronic kidney disease (CKD) and stable glycemic control who were already being treated with fixed doses of antihypertensive agents over a 24-week period. These agents were 80 mg of the angiotensin II receptor blocker (ARB) telmisartan and 5 mg of the calcium channel blocker (CCB) amlodipine. Patients were randomly assigned to two groups: the aliskiren group, receiving 150 mg per day aliskiren, which was increased to 300 mg per day (n=32), and the CCB group, which received an increased dose (7.5 mg per day) of amlodipine that was increased to 10 mg per day (n=32). Urinary albumin excretion and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and liver-type fatty acid-binding protein (L-FABP) were investigated in each group. Mean systolic and diastolic blood pressure decreased significantly in both groups, but there was no significant difference between the two groups at the end of the study. Serum creatinine levels and estimated glomerular filtration rate did not differ significantly between the two groups, but percent changes of urinary albumin/creatinine ratios, 8-OHdG and L-FABP levels decreased significantly in the aliskiren group compared with the CCB group. Plasma aldosterone levels were significantly decreased in the aliskiren group, which correlated significantly with those of urinary 8-OHdG and L-FABP. Our results suggest that the addition of aliskiren to the maximal recommended dose of ARB and usual dose of amlodipine is more effective in reducing albuminuria and oxidant stress in hypertensive diabetic patients with CKD than increasing the dose of amlodipine.
authors.affiliation: Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan. abe.masanori@nihon-u.ac.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Abe
authors.forename: Noriaki
authors.initials: N
authors.lastname: Maruyama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fujii
authors.forename: Midori
authors.initials: M
authors.lastname: Ito
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Okada
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000517:prevention & control; D000450:Aldosterone / Q000097:blood; D000577:Amides / Q000009:adverse effects / Q000627:therapeutic use*; D017311:Amlodipine / Q000627:therapeutic use; D057912:Angiotensin II Type 2 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D001565:Benzoates / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000652:urine; D005260:Female; D005650:Fumarates / Q000009:adverse effects / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D000077333:Telmisartan; D055815:Young Adult; D000092502:Renin Inhibitors
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000450:Aldosterone; D000577:Amides; D017311:Amlodipine; D057912:Angiotensin II Type 2 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D002121:Calcium Channel Blockers; D003849:Deoxyguanosine; D050556:Fatty Acid-Binding Proteins; D005650:Fumarates; D006442:Glycated Hemoglobin; D012083:Renin; D000077333:Telmisartan; D000092502:Renin Inhibitors; C446481:aliskiren