Search

A 12-month, multicenter (57 clinical institutions), randomized, open-labeled trial was undertaken to compare the efficacy of the angiotensin II receptor antagonist losartan and the calcium channel blocker amlodipine in patients with proteinuric chronic kidney disease (CKD) and hypertension. A total of 117 patients (79, chronic glomerulonephritis; 14, diabetic nephropathy; 24, other CKD) were randomly allocated into two treatment groups. Losartan and amlodipine exerted the same efficacy for blood pressure (BP) control; however, losartan significantly reduced the 24-h urinary protein excretion at months 3, 6, and 12, with the reduction of 20.7%, 35.2%, 35.8%, whereas amlodipine did not change the amount of proteinuria over the 12-month study period. When patients were stratified into groups according to the level of BP control at 3 months, the reduction in urinary protein excretion by losartan was evident in the group for which a BP of <140/90 mmHg was achieved, as well as in the group for which the goal BP (<130/85 mmHg) for treatment of CKD was not achieved. When patients were stratified according to baseline urinary protein excretion, those with > or = 2 g/day showed a reduction in proteinuria by losartan of 23.3%, 39.4%, and 47.9% at months 3, 6, and 12, and those with <2 g/day showed a reduction of 18.5% and 31.2% at months 3 and 6, respectively. No fatal adverse events were experienced in either drug group. We conclude that losartan reduced proteinuria in patients with CKD and hypertension. This positive effect may contribute to the renal protective benefit of losartan, and is beyond the magnitude of BP control.

Background: Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection., Methods: We examined the effect of the angiotensin (AT)1 receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] > or = 140 mmHg or diastolic blood pressure [DBP] > or = 90 mmHg) and CKD (male, body weight [BW] > or = 60 kg: 1.5 < or = SCr < 3.0 mg/dl; female or male BW < 60 kg: 1.3 < or = SCr < 3.0 mg/dl), manifesting proteinuria of 0.5 g or more/day. Losartan was administered once daily at doses of 25 to 100 mg/day, and amlodipine was given once daily at 2.5 to 5 mg/day. No antihypertensive combination therapy was allowed during the first 3-month period., Results: A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group ( n = 43), but there was no change in the amlodipine group ( n = 43). Analysis of stratified subgroups with proteinuria of 2 g or more/day and less than 2 g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2 g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period., Conclusions: Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.