Randomized, controlled study of the effects of losartan versus enalapril in small doses on proteinuria and tubular injury in primary glomerulonephritis.
ABSTRACT Pharmacological blockade of the renin-angiotensin-aldosteron system ameliorates glomerular and tubulointerstitial damage. For optimal renoprotection, high doses of angiotensin II converting enzyme inhibitors and angiotensin II subtype 1 receptor antagonists are commonly recommended, but cannot always be administered. The aim of this study was to evaluate the effects of low-dose (25 mg) losartan on proteinuria and tubular injury extent.
This was an open, randomized, 12-month study on the effects of 25 mg of losartan (n=19) vs. 10 mg of enalapril (n=14) as a control on proteinuria, urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), and blood pressure in patients with primary glomerulonephritis. The second part of the study was an uncontrolled assessment of the renal effects of 50-mg administration of losartan.
There were no significant differences between the groups in the effects on proteinuria and NAG excretion. Losartan and enalapril reduced proteinuria by 32.8% (p<0.029) and 40.9% (p<0.021), respectively, but did not affect NAG excretion. The antiproteinuric effect of losartan, achieved without changes in blood pressure, was particularly evident in subjects with proteinuria >1.5 g/24 h and normal blood pressure. 50 mg of losartan caused a significant decrease in NAG excretion vs. the baseline (p<0.027).
25 mg of losartan and 10 mg of enalapril equally reduce proteinuria. The significant antiproteinuric effect of losartan was achieved despite no changes in blood pressure. There were no differences between the drugs regarding their influence on tubular injury extent. 50 mg of losartan seems to be the minimal dose to improve tubular status.
- SourceAvailable from: Johannes F E Mann[Show abstract] [Hide abstract]
ABSTRACT: Reduction of proteinuria is associated with delayed progression of chronic kidney disease. Reports suggest that angiotensin-receptor blockers (ARBs) reduce proteinuria, but results are variable. The relative effect of ARBs and angiotensin-converting enzyme (ACE) inhibitors, and their combined administration, remains uncertain. To establish the effect of ARBs versus placebo and alternative treatments, and the effect of combined treatment with ARBs and ACE inhibitors, on proteinuria. English-language studies in MEDLINE and the Cochrane Library Central Register of Controlled Trials (January 1990 to September 2006), reference lists, and expert contacts. Randomized trials of ARBs versus placebo, ACE inhibitors, calcium-channel blockers, or the combination of ARBs and ACE inhibitors in patients with or without diabetes and with microalbuminuria or proteinuria for whom data were available on urinary protein excretion at baseline and at 1 to 12 months. Two investigators independently searched and abstracted studies. Forty-nine studies involving 6181 participants reported results of 72 comparisons with 1 to 4 months of follow-up and 38 comparisons with 5 to 12 months of follow-up. The ARBs reduced proteinuria compared with placebo or calcium-channel blockers over 1 to 4 months (ratio of means, 0.57 [95% CI, 0.47 to 0.68] and 0.69 [CI, 0.62 to 0.77], respectively) and 5 to 12 months (ratio of means, 0.66 [CI, 0.63 to 0.69] and 0.62 [CI, 0.55 to 0.70], respectively). The ARBs and ACE inhibitors reduced proteinuria to a similar degree. The combination of ARBs and ACE inhibitors further reduced proteinuria more than either agent alone: The ratio of means for combination therapy versus ARBs was 0.76 (CI, 0.68 to 0.85) over 1 to 4 months and 0.75 (CI, 0.61 to 0.92) over 5 to 12 months; for combination therapy versus ACE inhibitors, the ratio of means was 0.78 (CI, 0.72 to 0.84) over 1 to 4 months and 0.82 (CI, 0.67 to 1.01) over 5 to 12 months. The antiproteinuric effect was consistent across subgroups. Most studies were small, varied in quality, and did not provide reliable data on adverse drug reactions. Proteinuria reduction is only a surrogate for important progression of renal failure. The ARBs reduce proteinuria, independent of the degree of proteinuria and of underlying disease. The magnitude of effect is similar regardless of whether the comparator is placebo or calcium-channel blocker. Reduction in proteinuria from ARBs and ACE inhibitors is similar, but their combination is more effective than either drug alone. Uncertainty concerning adverse effects and outcomes that are important to patients limits applicability of findings to clinical practice.Annals of internal medicine 02/2008; 148(1):30-48. · 13.98 Impact Factor