Effects of Monotherapy of Temocapril or Candesartan with Dose Increments or Combination Therapy with Both Drugs on the Suppression of Diabetic Nephropathy

ArticleinHypertension Research 30(4):325-34 · May 2007with16 Reads
DOI: 10.1291/hypres.30.325 · Source: PubMed
Abstract
We examined the effects of increasing the recommended initial doses of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), or of switching to combination therapy with both drugs, on diabetic nephropathy. Hypertensive type 2 diabetic patients with urinary albumin excretion (ACR) between 100 and 300 mg/g creatinine (Cre) were assigned to the following five groups in which an antihypertensive drug was administered at a recommended initial dose for 48 weeks, and then either the dose was doubled or an additional drugs was added to regimen for the following 48 weeks: N, nifedipine-CR (N) 20 mg/day (initial dose); T, ACEI temocapril (T) 2 mg/day; C, ARB candesartan (C) 4 mg/day; T+C, T first and then addition of C; C+T, C first and then addition of C. ACR decreased in the T (n=34), C (n=40), T+C (n=37) and C+T (n=35) groups, but not in the N group (n=18). However, the anti-proteinuric effect was less in the T than in the C, T+C or C+T groups, while no differences existed among the latter three. In each group, there were significant linear relationships between attained BP and ACR; however, the regression lines were shifted toward lower ACR level in the renin-angiotensin system-inhibition groups compared with the N group. These results indicate that an ACEI and/or ARB is superior to a CCB in retarding diabetic nephropathy, while the combination of low doses of ACEI and ARB has effects similar to those of high-dose ARB. Even among patients treated with an ACEI and/or ARB, lowering BP is important.
    • "Ten studies [18, 21, 25, 27–29, 36, 38, 44, 45] reported regression of albuminuria (n03,710; ESMTable 6). The treatment effect between ACEI/ARB and other antihypertensive drugs, based on nine studies [18, 21, 25, 27, 28, 36, 38, 44, 45] (n0646 vs 640), was homogeneous (χ 2 08.74, df08, p00.365, I 2 08.4%) with a borderline non-significant effect of 16% (pooled RR01.16 [95% CI 0.99, 1.39]; seeTable 2 andFig. "
    Full-text · Article · Jun 2012
    • "Ten studies [18, 21, 25, 27–29, 36, 38, 44, 45] reported regression of albuminuria (n03,710; ESMTable 6). The treatment effect between ACEI/ARB and other antihypertensive drugs, based on nine studies [18, 21, 25, 27, 28, 36, 38, 44, 45] (n0646 vs 640), was homogeneous (χ 2 08.74, df08, p00.365, I 2 08.4%) with a borderline non-significant effect of 16% (pooled RR01.16 [95% CI 0.99, 1.39]; seeTable 2 andFig. "
    [Show abstract] [Hide abstract] ABSTRACT: This meta-analysis aimed to compare the renal outcomes between ACE inhibitor (ACEI)/angiotensin II receptor blocker (ARB) and other antihypertensive drugs or placebo in type 2 diabetes. Publications were identified from Medline and Embase up to July 2011. Only randomised controlled trials comparing ACEI/ARB monotherapy with other active drugs or placebo were eligible. The outcome of end-stage renal disease, doubling of serum creatinine, microvascular complications, microalbuminuria, macroalbuminuria and albuminuria regression were extracted. Risk ratios were pooled using a random-effects model if heterogeneity was present; a fixed-effects model was used in the absence of heterogeneity. Of 673 studies identified, 28 were eligible (n = 13-4,912). In direct meta-analysis, ACEI/ARB had significantly lower risk of serum creatinine doubling (pooled RR = 0.66 [95% CI 0.52, 0.83]), macroalbuminuria (pooled RR = 0.70 [95% CI 0.50, 1.00]) and albuminuria regression (pooled RR 1.16 [95% CI 1.00, 1.39]) than other antihypertensive drugs, mainly calcium channel blockers (CCBs). Although the risks of end-stage renal disease and microalbuminuria were lower in the ACEI/ARB group (pooled RR 0.82 [95% CI 0.64, 1.05] and 0.84 [95% CI 0.61, 1.15], respectively), the differences were not statistically significant. The ACEI/ARB benefit over placebo was significant for all outcomes except microalbuminuria. A network meta-analysis detected significant treatment effects across all outcomes for both active drugs and placebo comparisons. Our review suggests a consistent reno-protective effect of ACEI/ARB over other antihypertensive drugs, mainly CCBs, and placebo in type 2 diabetes. The lack of any differences in BP decrease between ACEI/ARB and active comparators suggest this benefit is not due simply to the antihypertensive effect.
    Full-text · Article · Dec 2011
    • "These data are consistent with the concept derived from recent in-vitro observations [31,32] that local activation of the RAS plays an important role in the progression of podocyte injury. The moderate effects of HRH on the progression of albuminuria might be simply associated with the reduction in BP, as suggested by recent clinical studies [33,34]. Glomerular sclerosis, which is characterized by mesangial matrix expansion, is observed in advanced diabetic nephropathy [13,14,16]. "
    [Show abstract] [Hide abstract] ABSTRACT: Clinical studies indicate that the remission, regression or both of nephrotic-range albuminuria are exerted by angiotensin II receptor blockers (ARBs) in diabetes. The current study was performed to test the hypothesis that these effects of ARBs are associated with regression of glomerular podocyte injury. We examined the effects of an ARB, olmesartan, on glomerular podocyte injury in type 2 diabetic Otsuka-Long-Evans-Tokushima-Fatty rats with overt albuminuria. At baseline (55-week-old), diabetic Otsuka-Long-Evans-Tokushima-Fatty rats showed severe albuminuria with desmin-positive areas (an index of podocyte injury) in both superficial and juxtamedullary glomeruli, and podocyte injury was much greater in juxtamedullary than in superficial glomeruli. At 75-week-old, Otsuka-Long-Evans-Tokushima-Fatty rats had developed more severe albuminuria and superficial glomerular podocyte injury, whereas juxtamedullary glomerular podocyte injury did not advance further. Olmesartan (10 mg/kg per day) decreased albuminuria and superficial glomerular desmin staining to levels that were lower than those at baseline, whereas advanced juxtamedullary glomerular podocyte injury was not changed. The current study demonstrates for the first time that juxtamedullary glomerular podocyte injury reaches a severe condition at an earlier time than superficial glomerular podocyte injury during the progression of overt albuminuria in type 2 diabetic rats. Our data also support the hypothesis that the antialbuminuric effects of ARBs are associated with regression of superficial glomerular podocyte injury in type 2 diabetes with nephrotic-range albuminuria.
    Full-text · Article · Nov 2010
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