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.
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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. · 16.10 Impact Factor
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ABSTRACT: Both enalapril and losartan are effective and widely used in patients with chronic kidney disease (CKD). This review aimed to evaluate the benefits of enalapril and losartan in adults with CKD. PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched, without language limitations, for randomized controlled trials (RCTs), in which enalapril and losartan were compared in adults with CKD. Standard methods, consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, were used. Reviewer Manager software, version 5.2, was used for meta-analysis. Of 318 citations retrieved, 17 RCTs (14 parallel-group and 3 crossover) met our inclusion criteria. The pooled analysis for parallel RCTs showed that the effects of enalapril and losartan on blood pressure, renal function and serum uric acid (UA) were similar. Meta-analysis indicated that patients taking enalapril had a higher risk of dry cough (risk ratio, 2.88; 95% CI, 1.11 to 7.48; P = 0.03). Sensitivity analysis showed well robustness of these findings. Enalapril has similar effects to losartan on systemic blood pressure, renal function and serum UA in patients with CKD, but carries a higher risk of dry cough. Larger trials are required to evaluate the effects of these medications on clinical outcomes.Nephrology 07/2013; 18(9). DOI:10.1111/nep.12134 · 1.86 Impact Factor
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ABSTRACT: Chronic kidney disease is a common disease. Most chronic kidney diseases evolve from primary glomerulonephritis. Proteinuria is an independent risk factor for the progression of chronic kidney disease. The general consensus is that therapy administered to decrease proteinuria should include steroids and/or immunosuppressants, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers. However, the side effects of, and adverse reactions to, these agents reduce the benefits to patients. In addition, the cost of these drugs is relatively high. Therefore, identification of inexpensive and effective drugs to decrease proteinuria is urgently needed. Shenyankangfu tablets have been a widely applied Chinese patent medicine for many years to decrease proteinuria. However, there is a lack of research-derived data regarding the clinical use. Therefore, we designed the present randomized controlled clinical trial to compare the efficacy and safety of Shenyankangfu tablets versus losartan potassium for control of proteinuria in patients with primary glomerulonephritis.Methods/design: This study will be a multicenter, prospective, double-blind, double-dummy, randomized controlled clinical trial. We will enroll 720 patients diagnosed with primary glomerulonephritis. The eligible patients will be randomly divided into the following groups at a 1:1:1:1:1 ratio: Shenyankangfu tablets group, losartan potassium 50 mg group, losartan potassium 100 mg group, Shenyankangfu tablets + losartan potassium 50 mg group, and Shenyankangfu tablets + losartan potassium 100 mg group. All groups will be followed up for 48 weeks; follow-up visits will be performed, at weeks 0, 4, 8, 12, 24, 36, and 48. The primary efficacy outcome will be the post-treatment change in the 24-hour proteinuria level, and the secondary efficacy outcomes will be the post-treatment changes in the serum creatinine level, estimated glomerular filtration rate, traditional Chinese medicine syndrome score, and serum albumin level. The results of this trial will provide solid data for use in evidence-based medicine with respect to the efficacy and safety of Shenyankangfu tablets for control of proteinuria in patients with primary glomerulonephritis compared to those of losartan potassium. Moreover, we infer that therapy comprising Shenyankangfu tablets + losartan potassium can decrease proteinuria to a larger extent than Shenyankangfu tablets or losartan potassium can alone.Trial registration: This trial was registered on 12 February 2014 at ClinicalTrials.gov (ID number NCT02063100).Trials 12/2014; 15(1):479. DOI:10.1186/1745-6215-15-479 · 2.12 Impact Factor