Combination therapy with an angiotensin-converting-enzyme inhibitor and an angiotensin II receptor antagonist ameliorates microinflammation and oxidative stress in patients with diabetic nephropathy.
OBJECTIVE
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.


METHODS
A total of 32 Japanese 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 (sICAM-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-OHdG) 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, sICAM-1 and IL-18, as well as urinary excretion of albumin, IL-18 and 8-OHdG decreased significantly in the combination therapy group at 48 weeks. The percent decreases in serum IL-18 concentrations and urinary IL-18 and 8-OHdG 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.
Osafune Clinic Okayama Japan ; Department of Internal Medicine Okayama Saiseikai General Hospital Okayama Japan.
Akihiko
A
Nakamura
Department of Medicine and Clinical Science Okayama Japan ; Center for Innovative Clinical Medicine Okayama University Hospital Okayama Japan.
Kenichi
K
Shikata
Department of Internal Medicine Okayama Saiseikai General Hospital Okayama Japan.
Tatsuaki
T
Nakatou
Department of Internal Medicine Okayama Saiseikai General Hospital Okayama Japan.
Takuya
T
Kitamura
Department of Internal Medicine Okayama Saiseikai General Hospital Okayama Japan ; Department of Medicine and Clinical Science Okayama Japan.
Nobuo
N
Kajitani
Department of Medicine and Clinical Science Okayama Japan ; Department of Diabetic Nephropathy Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama Japan.
Daisuke
D
Ogawa
Department of Medicine and Clinical Science Okayama Japan.
Hirofumi
H
Makino
Combination; Diabetic nephropathy; Renin–angiotensin system