Losartan in diabetic nephropathy

Area of Science:

• Nephrology
• Endocrinology
• Pharmacology

Background:

• Diabetic nephropathy is a leading cause of end-stage renal disease (ESRD).
• Angiotensin II plays a key role in the pathogenesis of diabetic nephropathy.
• Selective AT(1) receptor antagonists offer a potential therapeutic strategy.

Purpose of the Study:

• To evaluate the efficacy of losartan in reducing renal endpoints in patients with type 2 diabetes mellitus and proteinuria.
• To assess the impact of losartan on the progression of kidney disease and mortality.

Main Methods:

• The Reduction of Endpoints in Non insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) study was a pivotal, randomized, placebo-controlled trial.
• 1513 patients with type 2 diabetes mellitus and proteinuria received losartan (50 or 100 mg/day) or placebo.
• Primary endpoint was a composite of doubling of serum creatinine, ESRD, or death.

Main Results:

• Losartan significantly reduced the composite endpoint of doubling of serum creatinine, ESRD, or death compared to placebo (43.5% vs 47.1%, p = 0.02).
• Significant reductions were observed for doubling of serum creatinine (p = 0.006), ESRD (p = 0.002), and ESRD or death (p = 0.01) with losartan.
• No significant differences in overall mortality, cardiovascular morbidity, or mortality were observed between groups.
• Losartan also effectively reduced mean albumin excretion rate and showed comparable effects to enalapril on kidney function in other studies.

Conclusions:

• Losartan is effective in slowing the progression of kidney disease and reducing mortality in patients with type 2 diabetes mellitus and proteinuria.
• Losartan is a well-tolerated treatment option for this patient population.
• The findings support the use of losartan for renoprotection in diabetic nephropathy.