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 (Olmesartan 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 ≥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.
Similar content being viewed by others
Article PDF
References
Wakai K, Nakai S, Kikuchi K, et al: Trends in incidence of endstage renal disease in Japan, 1983–2000: age-adjusted and age-specific rates by gender and cause. Nephrol Dial Transplant 2004; 19: 2044–2052.
Japanese Society for Dialysis Therapy : Condition as of December 31, 2004, in: An Overview of Regular Dialysis Treatment in Japan. Japanese Society for Dialysis Therapy, 2004, pp 2–22 ( in Japanese).
Lui SF, Ho YW, Chau KF, Leung CB, Choy BY : Hong Kong Renal Registry 1995–1999. Hong Kong J Nephrol 1999; 1: 53–60.
Sarnak MJ, Levey AS, Schoolwerth AC, et al: Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003; 108: 2154–2169.
Levey AS, Beto JA, Coronado BE, et al: Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis 1998; 32: 853–906.
Wilmer WA, Rovin BH, Hebert CJ, et al: Management of glomerular proteinuria: a commentary. J Am Soc Nephrol 2003; 14: 3217–3232.
Campbell RC, Ruggenenti P, Remuzzi G : Halting the progression of chronic nephropathy. J Am Soc Nephrol 2002; 13: S190–S195.
Keane WF : Proteinuria: its clinical importance and role in progressive renal disease. Am J Kidney Dis 2000; 35 ( Suppl 1): S97–S105.
Ruggenenti P, Perna A, Mosconi L, et al: Proteinuria predicts endstage renal failure in non-diabetic chronic nephropathies. The “Gruppo Italiano di Studi Epidemiologici in Nefrologia” (GISEN). Kidney Int Suppl 1997; 63: S54–S57.
Brenner BM, Cooper ME, de Zeeuw D, et al: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–869.
Lewis EJ, Hunsicker LG, Clarke WR, et al: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–860.
Parving HH, Lehnert H, Brochner-Mortensen J, et al: The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345: 870–878.
Mogencen CE, Neldam S, Tikkanen I, et al: Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ 2000; 321: 1440–1444.
Viberti G, Wheeldon NM, MicroAlbuminuria Reduction with VALsartan (MARVAL) Study Investigators : Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation 2002; 106: 672–678.
Barnett AH, Bain SC, Bouter P, et al: Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med 2004; 351: 1952–1961.
Morrish NJ, Wang S, Stevens LK, Fuller JH, Keen H : Mortality and causes of death in the WHO Multinational Survey of Vascular Diseases in Diabetes. Diabetologia 2001; 44 ( Suppl 2): S14–S21.
Karter AJ, Ferrara A, Liu JY, et al: Ethnic disparities in diabetic complications in an insured population. JAMA 2002; 287: 2519–2527.
Chan JC, Wat NM, So WY, et al: Renin angiotensin aldosterone system blockade and renal disease in patients with type 2 diabetes. An Asian perspective from the RENAAL Study. Diabetes Care 2004; 27: 874–879.
Japanese Society of Hypertension Guidelines Subcommittee for the Management of Hypertension : Guidelines for the Management of Hypertension for General Practitioners. Hypertens Res 2001; 24: 613–634.
Giatras I, Lau J, Levey AS : Effect of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease: a meta-analysis of randomized trials. Angiotensin-Converting-Enzyme Inhibition and Progressive Renal Disease Study Group. Ann Intern Med 1997; 127: 337–345.
American Diabetes Association : Standards of Medical Care in Diabetes. Diabetes Care 2002; 25: 33S–49S.
American Diabetes Association : Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 2002; 25: 85S–89S.
Chobanian AV, Bakris GL, Black HR, et al: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: 2560–2572.
Strippoli GF, Craig M, Deeks JJ, et al: Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review. BMJ 2004; 329: 828.
Adler AI, Stratton IM, Neil HA, et al: Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 2000; 321: 412–419.
Chrysant SG, Marbury TC, Robinson TD : Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension. J Hum Hypertens 2003; 17: 425–432.
Oparil S, Williams D, Chrysant SG, Marbury TC, Neutel J : Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension. J Clin Hypertens 2001; 318: 283–291.
Taal MW, Brenner BM : Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int 2000; 57: 1803–1817.
Noris M, Remuzzi G : ACE inhibitors and AT1 receptor antagonists: is two better than one? Kidney Int 2002; 61: 1545–1547.
Siragy HM, de Gasparo M, El-Kersh M, et al: Angiotensin-converting enzyme inhibition potentiates angiotensin II type 1 receptor effects on renal bradykinin and cGMP. Hypertension 2001; 38: 183–186.
Wolf G, Ritz E : Combination therapy with ACE inhibitors and angiotensin II receptor blockers to halt progression of chronic renal disease: pathophysiology and indications. Kidney Int 2005; 67: 799–812.
Kuriyama S, Tomonari H, Tokudome G, et al: Antiproteinuric effects of combined antihypertensive therapies in patients with overt type 2 diabetic nephropathy. Hypertens Res 2002; 25: 849–855.
Hebert LA, Falkenhain ME, Nahman NS Jr, et al: Combination ACE inhibitor and angiotensin II receptor antagonist therapy in diabetic nephropathy. Am J Nephrol 1999; 19: 1–6.
Jacobsen P, Andersen S, Rossing K, et al: Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy. Kidney Int 2003; 63: 1874–1880.
Horita Y, Tadokoro M, Taura K, et al: Low-dose combination therapy with temocapril and losartan reduces proteinuria in normotensive patients with immunoglobulin A nephropathy. Hypertens Res 2004; 27: 963–970.
Nakao N, Yoshimura A, Morita H, et al: Combination treatment of angiotensin-II receptor blocker and angiotensin-converting–enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 2003; 361: 117–124.
Author information
Authors and Affiliations
Consortia
Corresponding author
Rights and permissions
About this article
Cite this article
Imai, E., Ito, S., Haneda, M. et al. Olmesartan Reducing Incidence of Endstage Renal Disease in Diabetic Nephropathy Trial (ORIENT): Rationale and Study Design. Hypertens Res 29, 703–709 (2006). https://doi.org/10.1291/hypres.29.703
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.29.703