Reduction and residual proteinuria are therapeutic targets in type 2 diabetes with overt nephropathy: A post hoc analysis (ORIENT-proteinuria)

Enyu Imai, Masakazu Haneda, Juliana C.N. Chan, Tetsu Yamasaki, Fumiaki Kobayashi, Sadayoshi Ito, Hirofumi Makino

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18 Citations (Scopus)

Abstract

BackgroundProteinuria 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).MethodsWe 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).ResultsCompared with the low group with baseline UPCR < 1.0g/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).ConclusionsIn 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.Trial registrationClinicalTrials. gov NCT00141453.

Original languageEnglish
Pages (from-to)2526-2534
Number of pages9
JournalNephrology Dialysis Transplantation
Volume28
Issue number10
DOIs
Publication statusPublished - Oct 1 2013

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Proteinuria
Type 2 Diabetes Mellitus
Creatinine
Proteins
Therapeutics
Diabetic Nephropathies
Kidney
Chronic Kidney Failure
Confidence Intervals
Disease Progression

Keywords

  • angiotensin receptor blocker
  • diabetic nephropathy
  • olmesartan
  • orient
  • residual proteinuria

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Reduction and residual proteinuria are therapeutic targets in type 2 diabetes with overt nephropathy : A post hoc analysis (ORIENT-proteinuria). / Imai, Enyu; Haneda, Masakazu; Chan, Juliana C.N.; Yamasaki, Tetsu; Kobayashi, Fumiaki; Ito, Sadayoshi; Makino, Hirofumi.

In: Nephrology Dialysis Transplantation, Vol. 28, No. 10, 01.10.2013, p. 2526-2534.

Research output: Contribution to journalArticle

Imai, Enyu ; Haneda, Masakazu ; Chan, Juliana C.N. ; Yamasaki, Tetsu ; Kobayashi, Fumiaki ; Ito, Sadayoshi ; Makino, Hirofumi. / Reduction and residual proteinuria are therapeutic targets in type 2 diabetes with overt nephropathy : A post hoc analysis (ORIENT-proteinuria). In: Nephrology Dialysis Transplantation. 2013 ; Vol. 28, No. 10. pp. 2526-2534.
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title = "Reduction and residual proteinuria are therapeutic targets in type 2 diabetes with overt nephropathy: A post hoc analysis (ORIENT-proteinuria)",
abstract = "BackgroundProteinuria 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).MethodsWe 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).ResultsCompared with the low group with baseline UPCR < 1.0g/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).ConclusionsIn 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.Trial registrationClinicalTrials. gov NCT00141453.",
keywords = "angiotensin receptor blocker, diabetic nephropathy, olmesartan, orient, residual proteinuria",
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T1 - Reduction and residual proteinuria are therapeutic targets in type 2 diabetes with overt nephropathy

T2 - A post hoc analysis (ORIENT-proteinuria)

AU - Imai, Enyu

AU - Haneda, Masakazu

AU - Chan, Juliana C.N.

AU - Yamasaki, Tetsu

AU - Kobayashi, Fumiaki

AU - Ito, Sadayoshi

AU - Makino, Hirofumi

PY - 2013/10/1

Y1 - 2013/10/1

N2 - BackgroundProteinuria 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).MethodsWe 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).ResultsCompared with the low group with baseline UPCR < 1.0g/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).ConclusionsIn 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.Trial registrationClinicalTrials. gov NCT00141453.

AB - BackgroundProteinuria 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).MethodsWe 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).ResultsCompared with the low group with baseline UPCR < 1.0g/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).ConclusionsIn 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.Trial registrationClinicalTrials. gov NCT00141453.

KW - angiotensin receptor blocker

KW - diabetic nephropathy

KW - olmesartan

KW - orient

KW - residual proteinuria

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DO - 10.1093/ndt/gft249

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SP - 2526

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SN - 0931-0509

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