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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00141453.
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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 diabeticpatients 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00141453.
Authors: Donald E Kohan; Hiddo J Lambers Heerspink; Blai Coll; Dennis Andress; John J Brennan; Dalane W Kitzman; Ricardo Correa-Rotter; Hirofumi Makino; Vlado Perkovic; Fan Fan Hou; Giuseppe Remuzzi; Sheldon W Tobe; Robert Toto; Hans-Henrik Parving; Dick de Zeeuw Journal: Clin J Am Soc Nephrol Date: 2015-07-07 Impact factor: 8.237
Authors: Martina Guthoff; Robert Wagner; Elko Randrianarisoa; Erifili Hatziagelaki; Andreas Peter; Hans-Ulrich Häring; Andreas Fritsche; Nils Heyne Journal: Sci Rep Date: 2017-01-16 Impact factor: 4.379