Open AccessCombination therapy with an angiotensin‐converting‐enzyme inhibitor and an angiotensin II receptor antagonist ameliorates microinflammation and oxidative stress in patients with diabetic nephropathy
Author(s) -
Nakamura Akihiko,
Shikata Kenichi,
Nakatou Tatsuaki,
Kitamura Takuya,
Kajitani Nobuo,
Ogawa Daisuke,
Makino Hirofumi
Publication year - 2013
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.12004
Subject(s) - medicine , losartan , combination therapy , diabetic nephropathy , pharmacology , nephropathy , ace inhibitor , diabetes mellitus , angiotensin receptor , endocrinology , angiotensin converting enzyme , urology , angiotensin ii , blood pressure
Aims/Introduction Recent studies have pointed to the effectiveness of combination therapy with an angiotensin‐converting‐enzyme inhibitor ( ACEI ) and an angiotensin receptor blocker ( ARB ) for diabetic nephropathy. However, some controversy over this combination treatment remains and the mechanisms underlying its renoprotective effects have not been fully clarified. Therefore, we compared the renoprotective effects of imidapril ( ACEI ) and losartan ( ARB ) combination therapy with losartan monotherapy in patients with diabetic nephropathy. We also compared the anti‐inflammatory and anti‐oxidative stress effects of these two treatments. Materials and Methods A total of 32 J apanese patients with type 2 diabetes and nephropathy were enrolled. Patients were randomized to either 100 mg/day losartan ( n = 16) or 50 mg/day losartan plus 5 mg/day imidapril ( n = 16). We evaluated clinical parameters, serum concentrations of high‐sensitivity C ‐reactive protein (hs‐ CRP ), soluble intercellular adhesion molecule‐1 (s ICAM ‐1), interleukin‐18 ( IL ‐18) and monocyte chemotactic protein‐1 ( MCP ‐1), and the urinary concentrations of IL ‐18, MCP ‐1 and 8‐hydroxy‐2′‐deoxyguanosine (8‐ OH d G ) at 24 and 48 weeks after starting treatment. Results Blood pressure was not significantly different between the two groups. The serum levels of hs‐ CRP , s ICAM ‐1 and IL‐18, as well as urinary excretion of albumin, IL ‐18 and 8‐ OH d G decreased significantly in the combination therapy group at 48 weeks. The percent decreases in serum IL ‐18 concentrations and urinary IL ‐18 and 8‐ OH d G were significantly greater in the combination therapy group than in the monotherapy group. Conclusions Combination therapy with an ACEI and an ARB could be beneficial for treating diabetic nephropathy through its anti‐inflammatory and anti‐oxidative stress effects.