title: Reduction and residual proteinuria are therapeutic targets in type 2 diabetes with overt nephropathy: a post hoc analysis (ORIENT-proteinuria).
abstract: BACKGROUND
  Proteinuria is a major predictor for progression of renal disease, including diabetic nephropathy. In a post hoc analysis of the ORIENT, a double-blinded randomized trial of 566 type 2 diabetic patients with nephropathy, we examined the risk association of composite renal outcome [end-stage renal disease, ESRD, doubling of serum creatinine (SCr) and death] with baseline, change and residual urinary protein/creatinine ratio (UPCR).
  
  
  METHODS
  We estimated the hazard ratios (HRs) with 95% confidence interval (CI) of composite renal outcome with baseline UPCR (low <1.0 g/gCr; moderate ≥ 1.0 g/gCr, <3.0 g/gCr and high ≥ 3.0 g/gCr) as well as percentage reduction of UPCR (Δ) (worsening: <0%; moderate: ≥ 0%, <30% and high ≥ 30%) and residual UPCR at 24 weeks (remission <1.0 g/gCr; moderate ≥ 1.0 g/gCr, <3.0 g/gCr and heavy ≥ 3.0 g/gCr).
  
  
  RESULTS
  Compared with the low group with baseline UPCR < 1.0 g/gCr, the respective HRs with 95% CI in the moderate and high UPCR groups were 3.02 (1.76-5.19) and 9.24 (5.43-15.73). Compared with patients with a worsening UPCR (<0%) at 24 weeks, the HR was 0.54 (0.39-0.74) in those with ≥ 0%, <30% ΔUPCR and 0.43 (0.31-0.61) in those with ≥ 30% ΔUPCR. Compared with the remission at 24 weeks, the HR was 2.12 (1.28-3.49) in moderate residual proteinuria and 4.59 (2.74-7.69) in heavy residual proteinuria. Compared with patients with residual UPCR ≥ 1.0 g/gCr and ΔUPCR <30%, the HR in those with ΔUPCR ≥ 30% and residual UPCR<1.0 g/gCr was 0.38 (0.22-0.64).
  
  
  CONCLUSIONS
  In patients with type 2 diabetes and overt nephropathy, over 30% reduction of UPCR compared with baseline and/or residual UPCR<1.0 g/gCr at 24 weeks predicted renoprotection. These values may be used as targets to guide anti-proteinuric and renoprotective therapy in diabetic nephropathy.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00141453.
authors.affiliation: Nakayamadera Imai Clinic, Takarazuka, Hyogo, Japan.
authors.forename: Enyu
authors.initials: E
authors.lastname: Imai
authors.forename: Masakazu
authors.initials: M
authors.lastname: Haneda
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Kobayashi
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: D003404:Creatinine / Q000097:blood; D048909:Diabetes Complications / Q000209:etiology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011507:Proteinuria / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D012074:Remission Induction; D012307:Risk Factors
chemical_list: D003404:Creatinine
keywords: angiotensin receptor blocker; diabetic nephropathy; olmesartan; orient; residual proteinuria