Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic nephropathy: Comparing telmisartan's and losartan's effects on proteinuria

Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA.
Kidney International (Impact Factor: 8.56). 09/2008; 74(3):364-9. DOI: 10.1038/ki.2008.204
Source: PubMed


In patients with diabetic nephropathy, lowering blood pressure and reducing proteinuria by over 30% correlates with a slower progression to kidney failure. We compared two different angiotensin receptor-blockers in a double blind, prospective trial of 860 patients with type 2 diabetes whose blood pressure levels was over 130/80 mmHg or who were receiving antihypertensive medication(s) and who had a morning spot urinary protein to creatinine ratio of 700 or more. Patients were randomized to telmisartan (a highly lipophilic agent with a long half-life) or losartan (with low lipophilicity and short half-life). The primary endpoint was the difference in the urinary albumin to creatinine ratio between the groups at 52 weeks. The geometric coefficient of variation and the mean of the urinary albumin to creatinine ratio fell in both groups at 52 weeks but both were significantly greater for the telmisartan compared to the losartan cohort. Mean systolic blood pressure reductions were not significantly different between groups at trial end. We conclude that telmisartan is superior to losartan in reducing proteinuria in hypertensive patients with diabetic nephropathy, despite a similar reduction in blood pressure.

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Available from: Ellen D Burgess, Jan 26, 2015
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    • "Many investigators have reported that blockage of the RAS by ARBs could maintain renal function in various types of nephropathy.12,13,21 In addition to examining chronic renal failure progression, a study used 5/6 nephrectomized rat models to clarify the renoprotective effects of ARBs in acute renal failure.22 "
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    ABSTRACT: The renoprotective function of the angiotensin II type 1 receptor blocker (ARB) is well-known in various studies, including the animal model of renal failure. However, detailed temporal changes of pathological and molecular findings after unilateral nephrectomy are not fully understood. The main purpose of this study was to clarify the renoprotective effects and pathological changes induced by the ARB in rat-remnant kidney (RK) tissues after unilateral nephrectomy, but not after a 5/6 nephrectomy. Telmisartan, which is structurally and functionally unique among ARB, was used in this study. Three rat groups were examined: A) no ARB administrated (RK, n=21); B) continuous subcutaneous infusion of an ARB administrated (RK-ARB, n=21); and C) a sham-operated group (Sham). Renal function was evaluated by blood urea nitrogen (BUN) levels and creatinine clearance (Ccr). Fibrosis was evaluated by hydroxyproline levels and Masson's trichrome staining. Expressions of angiotensin II type 1 receptor (AT1R) and transforming growth factor beta (TGF-β) were investigated by real-time polymerase chain reaction and Western blotting. There was no significant difference regarding body and kidney weight or pathological features evaluated by hematoxylin and eosin staining between the RK and RK-ARB groups. The Ccr in the RK group was significantly lower than that in the Sham group (P<0.01), but no significant difference was found between the RK-ARB and Sham groups. The fibrotic area increased significantly with time after nephrectomy in the RK group. Although a similar trend was found in the RK-ARB group, the percentage of fibrous area in the RK-ARB group was significantly lower than that in the RK group at each time point (P<0.01). AT1R mRNA levels in the RK group were regulated immediately compared with those in the RK-ARB group. Although expressions of the AT1R and TGF-β were significantly higher in the RK-ARB group than in the Sham group, no significant differences were found between the RK-ARB and Sham group. The ARB had renoprotective effects after unilateral nephrectomy. The ARB effectively maintained Ccr. Our results also showed the possibility that fibrotic changes mediated by AT1R and TGF-β play an important role in renal protection. Moreover, this is the first report on changes of AT1R expression after using the ARB telmisartan in kidney tissues after unilateral nephrectomy. Finally, our results suggest that ARB may be useful to prevent renal failure in patients treated with nephrectomy.
    International Journal of Nephrology and Renovascular Disease 10/2013; 6:207-14. DOI:10.2147/IJNRD.S51216
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    • "Mauer et al. showed that early administration of RAS blocking agents did not reduce DN progression.[17] However, the results of a cohort study by Bakris et al. showed that telmisartan was more effective than losartan in reducing microalbuminuria in type 2 diabetes.[18] "
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    ABSTRACT: This study aimed to investigate the beneficial effects of angiotensin receptor blockers (ARBs) on markers of endothelial function in patients with early stage of diabetic nephropathy (DN). This cross-sectional study was conducted on 32 participants with IDDM from January 2010 until May 2011 in Isfahan, Iran. The participants were candidate for receiving ARBs or angiotensin-converting enzyme inhibitors (ACEIs) to decrease microalbuminuria. The inclusion criteria were as follows: the age of onset of insulin-dependent diabetes mellitus (IDDM)less than 15 years; normal glomerular filtration rate (GFR); normal blood pressure; normal cardiovascular examination; negative urine culture, receiving no medications except insulin. Microalbuminuria was measured in two fasting urine samples with a sampling interval of at least 1-2 months by ELISA method. Patients with two abnormal results were included. Microalbumin to creatinin ratio equal to or more than 30 mg/gm was considered abnormal. The fasting blood samples to determine serum nitric oxide (NO) and vascular cell adhesion molecule (VCAM) were obtained at the time 0 (before starting the study), and after 2 months of receiving ARBmedication. Valsartan tablet (Diovan, Novartis Company) with a dose of 1 mg/kg/day up to 80 mg/day in a single dose was administered. Urine microalbumin to creatinin ratio after valsartan consumption was lower than microalbumin level before the medication, P < 0.05. After valsartan consumption, serum VCAM-1 level reduced and NO level increased significantly, P < 0.05. Angiotensin receptor blockers may reduce VCAM-1 and microalbuminuria and may increase NO levels in early stages of DN. Thus administration of ARBs might be considered even in early stages of DN.
    International journal of preventive medicine 07/2012; 3(7):477-82.
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    • "There is also emerging evidence that telmisartan, in contrast to losartan, reduces progression of carotid artery thickening as assessed by carotid intima-media thickening in patients receiving treatment with ARBs [Hasegawa et al. 2011]. Finally, as described above, telmisartan was superior to losartan in reducing proteinuria , a known surrogate for renal dysfunction in patients with high CV risk, within the AMADEO trial [Bakris et al. 2008]. "
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    ABSTRACT: For patients with hypertension, effective control of blood pressure (BP) reduces cardiovascular (CV), and renal risk. Antihypertensive agents that offer benefits that extend beyond those associated with BP reduction alone, to include tissue protective effects and effects on the vasculature, may be of benefit for many patients with increased CV risk due to comorbidities or prior history of CV events. Renin-angiotensin system (RAS) blockers [angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs)] are guideline-recognized, highly effective antihypertensive agents that exert their BP-lowering action through different mechanisms at different levels of the RAS. Large-scale clinical studies suggest that small, between-treatment differences in BP lowering do not account for observed outcome differences between RAS blockers and other antihypertensive agents. Analysis of data from seminal clinical studies and meta-analyses identify that, controlling for effects on BP control, RAS blockers may be more effective than calcium channel blockers (CCBs) in reducing risk of myocardial infarction and congestive heart failure; ARBs may be more effective than either ACEIs or β blockers in stroke prevention; CCBs may be more effective than RAS blockers in stroke prevention; and ARBs may be more effective than β blockers in reducing left ventricular hypertrophy. This review considers the rationale and evidence for benefits of RAS blockade beyond BP lowering, and highlights the differences between ARBs and ACEIs, and between agents within these drug classes.
    Therapeutic Advances in Cardiovascular Disease 04/2012; 6(2):81-91. DOI:10.1177/1753944712444866 · 2.13 Impact Factor
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