Renoprotective Effect of the Addition of Losartan to Ongoing Treatment with an Angiotensin Converting Enzyme Inhibitor in Type-2 Diabetic Patients with Nephropathy

Abstract

Angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are frequently used for the treatment for glomerulonephritis and diabetic nephropathy because of their albuminuria-or proteinuria-reducing effects. To many patients who are nonresponsive to monotherapy with these agents, combination therapy appears to be a good treatment option. In the present study, we examined the effects of the addition of an ARB (losartan) followed by titration upon addition and at 3 and 6 months (n =14) and the addition of an ACE-I followed by titration upon addition and at 3 and 6 months (n =20) to the drug regimen treatment protocol in type 2 diabetic patients with nephropathy for whom more than 3-month administration of an ACE-I or the combination of an ACE-I plus a conventional antihypertensive was ineffective to achieve a blood pressure (BP) of 130/80 mmHg and to reduce urinary albumin to <30 mg/day. During the 12-month treatment, addition of losartan or addition of an ACE-I to the treatment protocol reduced systolic blood pressure (SBP) by 10% and 12%, diastolic blood pressure (DBP) by 7% and 4%, and urinary albumin excretion by 38% and 20% of the baseline value, respectively. However, the effects on both BP and urinary albumin were not significantly different between the two therapies. In conclusion, addition of losartan or an ACE-I to an ongoing treatment with an ACE-I, or addition of an ACE-I to ongoing treatment with a conventional antihypertensive were equally effective at reducing the urinary albumin excretion and BP, and

Direct Evidence for Intrarenal Chymase-Dependent Angiotensin II Formation on the Diabetic Renal Microvasculature

“…Our studies may provide a potential mechanism involved in the superior renoprotective effects of combining an ACE inhibitor with an AT 1 receptor antagonist relative to ACE inhibitor therapy alone in patients with DN which has been reported in some clinical studies. 43,44 In addition, the presence of this ACE-independent pathway for ANGII formation may explain the continued proteinuria in some patients on maximal ACE inhibitor therapy. 45 However, the ONTARGET trial indicated that in patients with cardiovascular disease or diabetes, the combination of ANG receptor blocker and ACE inhibitor provided more adverse events without an increase in benefit compared to either monotherapy.…”

Renin–angiotensin–aldosterone system genotypes and haplotypes affect the susceptibility to nephropathy in type 2 diabetes patients

“…13,14 Increasing body of evidence implicates RAAS in DN pathogenesis. 8,15,16 This was based on the findings that ANG II induces progressive renal injury in DN, in part by increasing cellular growth and proliferation and matrix synthesis, leading to glomerular sclerosis. 17 Blockade of RAAS by ACE-I and ARBs prevented structural and functional changes in the diabetic kidney, further establishing a role for RAAS in DN.…”

Irbesartan and Hydrochlorothiazide Association in the Treatment of Hypertension

“…Losartan add-on therapy resulted in a significant decrease in serum uric acid levels, although the baseline level of uric acid was within the normal range in the study patients [53]. Losartan possesses an uricosuric effect both after single and multiple doses, increasing urinary excretion of uric acid dose-dependently [54].…”