title: Identification of the stages of diabetic nephropathy at which angiotensin II receptor blockers most effectively suppress albuminuria.
abstract: BACKGROUND
  It is unclear when angiotensin II receptor blockers (ARBs) produce their strongest antialbuminuric effect (AAE) in patients with diabetic nephropathy. ARBs produce stronger AAEs when urinary excretion of reactive oxygen species (ROS) and/or of angiotensinogen (AGT) is higher before treatment, although the relationship between ROS, AGT, and the urinary albumin-to-creatinine ratio (ACR) is unclear. We sought to define the relationship between ROS and ACR and establish the stage at which ARBs exert maximal AAEs.
  
  
  METHODS
  Urinary ROS and AGT and the ACR were measured in 277 hypertensive type 2 diabetic patients before ARB treatment, and changes in the ACR were analyzed over 16 weeks.
  
  
  RESULTS
  Urinary AGT and ROS showed similar changes as the disease progressed, and the increase in ACR often observed in patients with lower ROS and AGT reflects the mild AAE produced by ARBs. ROS and AGT levels and the AAE were all highest in albuminuric patients (ACR = 30-1,000 mg/g creatinine), whereas normoalbuminuric patients (ACR < 30mg/g creatinine) displayed variable ROS values and AAEs. Glycemic control exerted a stronger AAE than ARBs in normoalbuminuric patients, whereas it had a weak AAE in most nephrotic (ACR ≥ 1,000 mg/g creatinine) patients, who had low basal ROS and AGT values. Lowering blood pressure was effective at all stages and appeared to promote an AAE, even in nephrotic patients.
  
  
  CONCLUSIONS
  ARBs produce a maximal AAE in albuminuric patients, and lowering blood pressure enhances the AAE in patients at all stages, including the nephrotic stage.
authors.affiliation: Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ogawa
authors.forename: Masato
authors.initials: M
authors.lastname: Matsushima
authors.forename: Takefumi
authors.initials: T
authors.lastname: Mori
authors.forename: Masashi
authors.initials: M
authors.lastname: Okamura
authors.forename: Miho
authors.initials: M
authors.lastname: Senda
authors.forename: Takuya
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nako
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
mesh_terms: D000419:Albuminuria / Q000517:prevention & control*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000808:Angiotensinogen / Q000652:urine; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000652:urine
chemical_list: D057911:Angiotensin Receptor Antagonists; D017382:Reactive Oxygen Species; D000808:Angiotensinogen; D003404:Creatinine
keywords: albuminuria; angiotensin II receptor blockers; angiotensinogen; blood pressure; diabetic nephropathy; hypertension; oxidative stress.