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

Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University School of Medicine, Sendai, Japan.
Hypertension Research (Impact Factor: 2.66). 05/2007; 30(4):325-34. DOI: 10.1291/hypres.30.325
Source: PubMed


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.

Full-text preview

Available from:
  • Source
    • "The progression of proteinuria increases the risk of renal and cardiovascular diseases in type 2 diabetes. In type 2 diabetic hypertensive patients, treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II (AngII) type 1 receptor blockers (ARBs) is more effective in reducing proteinuria than other traditional antihypertensive therapies (Sasso et al., 2002; Ogawa et al., 2007), suggesting the blood pressure-independent antiproteinuric effects of AngII blockade. Other studies have demonstrated that remission of nephrotic-range proteinuria with ACEIs is associated with substantial reductions in the risk of renal and cardiovascular events, leading to greatly improved survival in type 2 diabetic patients (Rossing et al., 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Treatment with angiotensin II type 1 receptor blockers (ARBs) is the first-line therapy for hypertensive patients with diabetic nephropathy. However, emerging clinical evidence indicates that mineralocorticoid receptor (MR) blockers have blood pressure-independent antiproteinuric effects. We sought to determine whether treatment with an MR blocker, eplerenone, enhances the effects of an ARB, telmisartan, on podocyte injury and proteinuria in type 2 diabetic Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats. From 20 to 50 weeks old, diabetic OLETF rats showed higher systolic blood pressure (SBP) and urinary protein excretion (U(protein)V) than nondiabetic control Long-Evans-Tokushima-Otsuka rats. At 50 weeks old, OLETF rats also showed glomerular sclerosis and podocyte injury, whereas nephrin and podocin mRNA levels in isolated glomeruli were significantly decreased. Treatment with telmisartan (3 mg/kg/day p.o.) decreased SBP and U(protein)V, increased nephrin and podocin mRNA levels, and attenuated glomerular sclerosis and podocyte injury. Eplerenone (100 mg/kg/day p.o.) did not alter SBP but elicited similar changes in renal parameters. However, greater reductions in U(protein)V and podocyte injury and greater increases in nephrin and podocin mRNA levels were observed in the combination treatment group. Hydralazine (25 mg/kg/day p.o.) decreased SBP but did not alter any renal parameters. These data indicate that MR blockade enhances the SBP-independent antiproteinuric effect of an ARB through inhibiting podocyte injury in type 2 diabetic rats.
    Preview · Article · Nov 2009 · Journal of Pharmacology and Experimental Therapeutics
  • [Show abstract] [Hide abstract]
    ABSTRACT: Evidence from recent studies indicates that in patients with diabetic nephropathy combined therapy with ACE inhibitors (ACEI) and AT1-receptor antagonists (ARB) results in more complete blockade of the renin–angiotensin–aldosterone system (RAS) than monotherapy, and reduces proteinuria. Most of these trials, however, had short follow-up, included a small number of patients, and were heterogeneous, so the opportunity to start this treatment in these patients remains unclear. This review summarizes the results of these studies, describing the renal effects of dual RAS blockade in both type 1 and type 2 diabetic patients.
    No preview · Article · Nov 2007 · Nature Clinical Practice Nephrology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The relative effectiveness of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) for lowering blood pressure is unknown. To compare the benefits and harms of ACE inhibitors versus ARBs for treating essential hypertension in adults. MEDLINE (1966 to May 2006), the Cochrane Central Register of Controlled Trials (Issue 2, 2006), and selected reference lists were searched for relevant English-language trials. The MEDLINE search was updated to August 2007 to identify head-to-head trials that reported blood pressure outcomes and major cardiovascular events. 61 clinical studies that directly compared ACE inhibitors versus ARBs in adult patients with essential hypertension, reported an outcome of interest, lasted at least 12 weeks, and included at least 20 patients. A standardized protocol with predefined criteria was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality and applicability; and assess the strength of the body of evidence for key outcomes. ACE inhibitors and ARBs had similar long-term effects on blood pressure (50 studies; strength of evidence, high). No consistent differential effects were observed for other outcomes (few studies reported long-term outcomes), including death, cardiovascular events, quality of life, rate of single antihypertensive agent use, lipid levels, progression to diabetes, left ventricular mass or function, and kidney disease. Consistent fair- to good-quality evidence showed that ACE inhibitors were associated with a greater risk for cough. There were fewer withdrawals due to adverse events and greater persistence with therapy for ARBs than for ACE inhibitors, although this evidence was not definitive. Patient subgroups for whom ACE inhibitors or ARBs were more effective, associated with fewer adverse events, or better tolerated were not identified. Few studies involved a representative sample treated in a typical clinical setting over a long duration, treatment protocols had marked heterogeneity, and substantive amounts of data about important outcomes and patient subgroups were missing. Available evidence shows that ACE inhibitors and ARBs have similar effects on blood pressure control, and that ACE inhibitors have higher rates of cough than ARBs. Data regarding other outcomes are limited.
    Full-text · Article · Feb 2008 · Annals of internal medicine
Show more