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

Abstract

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. A total of 32 Japanese patients with type2 diabetes and nephropathy were enrolled. Patients were randomized to either 100mg/day losartan (n=16) or 50mg/day losartan plus 5mg/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 48weeks after starting treatment. 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 48weeks. 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. Combination therapy with an ACEI and an ARB could be beneficial for treating diabetic nephropathy through its anti-inflammatory and anti-oxidative stress effects.