TY - JOUR
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
N1 - Funding Information:
The ORIENT study was supported by a research grant from Daiichi Sankyo Co.
PY - 2013/10
Y1 - 2013/10
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
UR - http://www.scopus.com/inward/record.url?scp=84884935013&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884935013&partnerID=8YFLogxK
U2 - 10.1093/ndt/gft249
DO - 10.1093/ndt/gft249
M3 - Article
C2 - 24013685
AN - SCOPUS:84884935013
VL - 28
SP - 2526
EP - 2534
JO - Proceedings of the European Dialysis and Transplant Association - European Renal Association. European Dialysis and Transplant Association - European Renal Association. Congress
JF - Proceedings of the European Dialysis and Transplant Association - European Renal Association. European Dialysis and Transplant Association - European Renal Association. Congress
SN - 0931-0509
IS - 10
ER -