Does losartan (Cozaar) slow the progression of renal disease in patients with type 2 diabetes and nephropathy?

BACKGROUND: Interruption of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors is renoprotective both in patients with type 1 diabetes and in patients without diabetes who have overt nephropathy. This study evaluates the effectiveness of losartan, an angiotensin-receptor blocker (ARB), in slowing the progression of nephropathy in type 2 diabetes.

POPULATION STUDIED: The Reduction of Endpoints in Non-insulin– dependent diabetes with the Angiotensin II Antagonist Losartan (RENAAL) study included 1513 people with type 2 diabetes and nephropathy, ranging in age from 31 to 70 years. Nephropathy was defined as urinary protein excretion of at least 500 mg daily and a serum creatinine of 1.3 to 3.0 mg per dL. Patients were excluded if they had a diagnosis of nondiabetic nephropathy; had experienced a recent myocardial infarction, transient ischemic attack, or stroke; had recently undergone coronary artery bypass grafting or percutaneous coronary angioplasty; or had ever had heart failure.

STUDY DESIGN AND VALIDITY: The RENAAL study was a double-blind randomized placebo-controlled trial in which patients were assigned to receive either losartan 50 to 100 mg or placebo. All patients received other antihypertensive therapy (excluding ACE inhibitors and ARBs) as necessary to maintain a blood pressure level of less than 140/90 mm Hg. The groups were similar at baseline, with a mean serum creatinine was 1.9 mg per dL (standard deviation = 0.5). The patients were followed up for a mean of 3.4 years, and an intention-to-treat analysis was reported. The study methods appeared valid, although concealment of allocation was not described.

OUTCOMES MEASURED: The primary outcome was the combined outcomes of a doubling of the baseline serum creatinine concentration, end-stage renal disease, and death.

RESULTS: Treatment with losartan resulted in a 16% reduction in the primary composite end point (95% confidence interval [CI], 2%-28%; P =.02; number needed to treat [NNT]=28). The risk for doubling of serum creatinine concentration was reduced by 25% (95% CI, 8-39; P =.006; NNT=23). The likelihood of reaching end-stage renal disease was reduced by 28% (95% CI, 11-42; P =.002; NNT=17). Losartan also decreased the level of proteinuria by 35% (P < .001) and the rate of decline of renal function by 18% (P =.01). A 32% reduction in a patient’s first hospitalization for heart failure was observed (P =.005). There was no difference in the composite end point of morbidity and mortality due to cardiovascular causes, adverse events, or overall mortality.

BACKGROUND: Interruption of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors is renoprotective both in patients with type 1 diabetes and in patients without diabetes who have overt nephropathy. This study evaluates the effectiveness of losartan, an angiotensin-receptor blocker (ARB), in slowing the progression of nephropathy in type 2 diabetes.

POPULATION STUDIED: The Reduction of Endpoints in Non-insulin– dependent diabetes with the Angiotensin II Antagonist Losartan (RENAAL) study included 1513 people with type 2 diabetes and nephropathy, ranging in age from 31 to 70 years. Nephropathy was defined as urinary protein excretion of at least 500 mg daily and a serum creatinine of 1.3 to 3.0 mg per dL. Patients were excluded if they had a diagnosis of nondiabetic nephropathy; had experienced a recent myocardial infarction, transient ischemic attack, or stroke; had recently undergone coronary artery bypass grafting or percutaneous coronary angioplasty; or had ever had heart failure.

STUDY DESIGN AND VALIDITY: The RENAAL study was a double-blind randomized placebo-controlled trial in which patients were assigned to receive either losartan 50 to 100 mg or placebo. All patients received other antihypertensive therapy (excluding ACE inhibitors and ARBs) as necessary to maintain a blood pressure level of less than 140/90 mm Hg. The groups were similar at baseline, with a mean serum creatinine was 1.9 mg per dL (standard deviation = 0.5). The patients were followed up for a mean of 3.4 years, and an intention-to-treat analysis was reported. The study methods appeared valid, although concealment of allocation was not described.

OUTCOMES MEASURED: The primary outcome was the combined outcomes of a doubling of the baseline serum creatinine concentration, end-stage renal disease, and death.

RESULTS: Treatment with losartan resulted in a 16% reduction in the primary composite end point (95% confidence interval [CI], 2%-28%; P =.02; number needed to treat [NNT]=28). The risk for doubling of serum creatinine concentration was reduced by 25% (95% CI, 8-39; P =.006; NNT=23). The likelihood of reaching end-stage renal disease was reduced by 28% (95% CI, 11-42; P =.002; NNT=17). Losartan also decreased the level of proteinuria by 35% (P < .001) and the rate of decline of renal function by 18% (P =.01). A 32% reduction in a patient’s first hospitalization for heart failure was observed (P =.005). There was no difference in the composite end point of morbidity and mortality due to cardiovascular causes, adverse events, or overall mortality.

BACKGROUND: Interruption of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors is renoprotective both in patients with type 1 diabetes and in patients without diabetes who have overt nephropathy. This study evaluates the effectiveness of losartan, an angiotensin-receptor blocker (ARB), in slowing the progression of nephropathy in type 2 diabetes.

POPULATION STUDIED: The Reduction of Endpoints in Non-insulin– dependent diabetes with the Angiotensin II Antagonist Losartan (RENAAL) study included 1513 people with type 2 diabetes and nephropathy, ranging in age from 31 to 70 years. Nephropathy was defined as urinary protein excretion of at least 500 mg daily and a serum creatinine of 1.3 to 3.0 mg per dL. Patients were excluded if they had a diagnosis of nondiabetic nephropathy; had experienced a recent myocardial infarction, transient ischemic attack, or stroke; had recently undergone coronary artery bypass grafting or percutaneous coronary angioplasty; or had ever had heart failure.

STUDY DESIGN AND VALIDITY: The RENAAL study was a double-blind randomized placebo-controlled trial in which patients were assigned to receive either losartan 50 to 100 mg or placebo. All patients received other antihypertensive therapy (excluding ACE inhibitors and ARBs) as necessary to maintain a blood pressure level of less than 140/90 mm Hg. The groups were similar at baseline, with a mean serum creatinine was 1.9 mg per dL (standard deviation = 0.5). The patients were followed up for a mean of 3.4 years, and an intention-to-treat analysis was reported. The study methods appeared valid, although concealment of allocation was not described.

OUTCOMES MEASURED: The primary outcome was the combined outcomes of a doubling of the baseline serum creatinine concentration, end-stage renal disease, and death.

RESULTS: Treatment with losartan resulted in a 16% reduction in the primary composite end point (95% confidence interval [CI], 2%-28%; P =.02; number needed to treat [NNT]=28). The risk for doubling of serum creatinine concentration was reduced by 25% (95% CI, 8-39; P =.006; NNT=23). The likelihood of reaching end-stage renal disease was reduced by 28% (95% CI, 11-42; P =.002; NNT=17). Losartan also decreased the level of proteinuria by 35% (P < .001) and the rate of decline of renal function by 18% (P =.01). A 32% reduction in a patient’s first hospitalization for heart failure was observed (P =.005). There was no difference in the composite end point of morbidity and mortality due to cardiovascular causes, adverse events, or overall mortality.