title: Renin angiotensin aldosterone system blockade and renal disease in patients with type 2 diabetes: a subanalysis of Japanese patients from the RENAAL study.
abstract: BACKGROUND
  The Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study has previously shown losartan to confer significant benefits to patients with type 2 diabetes and nephropathy. The original study of 1513 patients included 96 Japanese patients; the present study is a post-hoc analysis of the effects of losartan in this Japanese subpopulation.
  
  
  METHODS
  This double-blind, randomized study compared losartan (50 to 100 mg once daily) with placebo. The study medication was taken in addition to conventional antihypertensive treatment, and the mean follow-up period for the Japanese patients was 2.8 years. The primary endpoint was the composite of doubling of serum creatinine, endstage renal disease, or death. Secondary endpoints included changes in proteinuria levels. Safety was also evaluated.
  
  
  RESULTS
  The primary composite endpoint was reached in fewer Japanese patients receiving losartan than placebo (50.0% versus 65.4%, respectively). The treatment effects of losartan were more robust when data were corrected for differences in proteinuria at baseline--a significant relative risk reduction of 45% with losartan (P=0.0397) was apparent. Treatment benefit exceeded that attributable to blood pressure changes alone. Levels of proteinuria were reduced with losartan compared with placebo, with an overall losartan treatment effect of 37.8% (P<0.001). Overall, losartan was similarly well tolerated in both the Japanese patients and the total population.
  
  
  CONCLUSIONS
  In Japanese patients with type 2 diabetes and nephropathy, losartan offers renal protection and is generally well tolerated.
authors.affiliation: Research Center for Advanced Science and Technology of the University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8904, Japan, and The Prince of Wales Hospital, Hong Kong, China. kurokawa@is.icc.u-tokai.ac.jp
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
authors.forename: William F
authors.initials: WF
authors.lastname: Keane
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Shahinfar
authors.forename: Zhongxin
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D057911:Angiotensin Receptor Antagonists; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000208:ethnology; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology / Q000209:etiology / Q000517:prevention & control; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007564:Japan / Q000208:ethnology; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology / Q000209:etiology / Q000517:prevention & control; D007676:Kidney Failure, Chronic / Q000517:prevention & control; D019808:Losartan / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000517:prevention & control; D011945:Receptors, Angiotensin / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D003404:Creatinine; D019808:Losartan