Combination Therapy More Renoprotective for Diabetics Than Monotherapy

The clinical effectiveness of combination therapy warrants its application to diabetic kidney disease and may contribute to amelioration of the prognosis of the disease. Combination therapy with an ACE inhibitor and an angiotensin-receptor blocker (ARB) appears to have a stronger renoprotective effect than monotherapy with either drug, even when the two drugs are each given at half the normal dose, Japanese researchers report.

Both ACE inhibitors and ARB have renoprotective effects in diabetic kidney disease, Dr. Hiroshi Ikegami of the Osaka University Graduate School of Medicine and colleagues note in their report in the January issue of the American Journal of Hypertension.

New research shows the two classes of drugs have different pathways of action beyond their effects on the renin-angiotensin system. Specifically, ACE inhibitors target the kallikrein-kinin system involved in vasoconstriction, Dr. Ikegami’s group explains, while ARBs can block angiotensin II produced independently of ACE.

The researchers determined whether combining a half-dose of each drug would be more beneficial than monotherapy in patients with diabetic kidney disease.

Twenty-seven patients with type 2 diabetes, all of whom had been on 10 mg imidapril or 8 mg candesartan for longer than 3 months, were switched to 5 mg imidapril and 4 mg candesartan daily. The researchers measured urinary albumin index (UAI) and blood pressure at baseline and after 3 months on the combination regimen.

While there was not a significant change in blood pressure, the researchers found, average UAI was reduced from 79.4 mg/g Cre to 52.5 mg/g Cre.

"It is speculated that potentially more effective inhibition of the renin-angiotensin system by the combination has a predominantly vasodilatory effect on efferent arterioles, leading to a reduction in intraglomerular pressure and thus to renoprotection," they write.

The researchers conclude: "The clinical effectiveness of combination therapy that we report here further warrants its application to diabetic kidney disease and may contribute to amelioration of the prognosis of the disease."
Am J Hypertens 2005;18:13-17.