Article

Olmesartan reducing incidence of endstage renal disease in diabetic nephropathy trial (ORIENT): rationale and study design.

Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan.
Hypertension Research (Impact Factor: 2.79). 09/2006; 29(9):703-9. DOI: 10.1291/hypres.29.703
Source: PubMed

ABSTRACT Diabetic nephropathy (DN) is a leading cause of endstage renal disease (ESRD) in Japan and Hong Kong. Asian patients are known to be more predisposed to DN and ESRD than Caucasians. Strict blood glucose and blood pressure control are key factors in prevention and treatment of DN. In the last decade, inhibition of the renin-angiotensin-aldosterone (RAA) system has been confirmed to reduce the incidence of cardiovascular complications in Caucasian patients with diabetes. Although the RENAAL study has demonstrated the beneficial effects of inhibition of the RAA system on prevention of ESRD and death in type 2 diabetic patients with overt proteinuria, only 17% of patients in this multicenter study were of Asian ethnicity. Given the predilection of Asian diabetic patients for renal complications and the rising burden of ESRD, there is a need to confirm these findings in a homogenous group of Asian patients. The ORIENT (Omesartan Reducing Incidence of Endstage Renal Disease in Diabetic Nephropathy Trial) is a randomized, double-blind, placebo-controlled study in Japan and Hong Kong to evaluate the renal protective benefits of olmesartan medoxomil in type 2 diabetic patients with overt proteinuria (urinary albumin to creatinine ratio > or =300 mg/g creatinine) and renal insufficiency (serum creatinine: 1.0-2.5 mg/dl). The study has a targeted enrollment of 400 Japanese and Hong Kong Chinese patients. The primary outcome is the composite endpoint of time to the first occurrence of doubling of serum creatinine, ESRD (serum creatinine more than 5.0 mg/dl, the need for chronic dialysis, or renal transplantation) or death. The average follow-up period is 4 years and the study ends in 2009.

0 Bookmarks
 · 
103 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The renal and cardiovascular protective effects of angiotensin receptor blocker (ARB) remain controversial in type 2 diabetic patients treated with a contemporary regimen including an angiotensin converting enzyme inhibitor (ACEI). We examined the effects of olmesartan, an ARB, on primary composite outcome of doubling of serum creatinine, endstage renal disease and death in type 2 diabetic patients with overt nephropathy. Secondary outcome included composite cardiovascular outcomes, changes in renal function and proteinuria. Randomisation and allocation to trial group were carried out by a central computer system. Participants, caregivers, the people carrying out examinations and people assessing the outcomes were blinded to group assignment. Five hundred and seventy-seven (377 Japanese, 200 Chinese) patients treated with antihypertensive therapy (73.5% [n = 424] received concomitant ACEI), were given either once-daily olmesartan (10-40 mg) (n = 288) or placebo (n = 289) over 3.2 ± 0.6 years (mean±SD). In the olmesartan group, 116 developed the primary outcome (41.1%) compared with 129 (45.4%) in the placebo group (HR 0.97, 95% CI 0.75, 1.24; p = 0.791). Olmesartan significantly decreased blood pressure, proteinuria and rate of change of reciprocal serum creatinine. Cardiovascular death was higher in the olmesartan group than the placebo group (ten vs three cases), whereas major adverse cardiovascular events (cardiovascular death plus non-fatal stroke and myocardial infarction) and all-cause death were similar between the two groups (major adverse cardiovascular events 18 vs 21 cases, all-cause deaths; 19 vs 20 cases). Hyperkalaemia was more frequent in the olmesartan group than the placebo group (9.2% vs 5.3%). Olmesartan was well tolerated but did not improve renal outcome on top of ACEI. Trial registration: ClinicalTrials.gov NCT00141453.
    Diabetologia 12/2011; 54(12):2978-86. · 6.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Microalbuminuria is a major target of the therapeutic interventions in clinical trials aimed at assessing whether and to what extent antihypertensive treatment can favor the regression and/or slow down the progression of renal dysfunction in cardiometabolic disease. The Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention (ROADMAP) trial has recently investigated the impact of an angiotensin II receptor blocker (olmesartan) on the new onset of microalbuminuria in type 2 diabetic patients, thus providing direct information on the ability of the drug to prevent the development of this marker of renal organ damage and, more generally, of cardiovascular risk. The results provide evidence that pharmacological blockade of angiotensin II receptors is highly effective in reducing the risk of developing microalbuminuria and that this effect can be achieved through blood-pressure-dependent and blood-pressure-independent effects. Despite the nephroprotective properties of olmesartan, the drug did not reduce the number of cardiovascular events and cardiovascular complications associated with the diabetic state.
    Expert Opinion on Pharmacotherapy 07/2011; 12(15):2421-4. · 2.86 Impact Factor
  • Source
    Revista Espanola de Cardiologia 05/2012; 65(7):678-9; author reply 679-80. · 3.20 Impact Factor

Full-text

View
2 Downloads
Available from