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

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). 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 () (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). Compared 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 (1.765.19) and 9.24 (5.4315.73). Compared with patients with a worsening UPCR (0) at 24 weeks, the HR was 0.54 (0.390.74) in those with 0, 30 UPCR and 0.43 (0.310.61) in those with 30 UPCR. Compared with the remission at 24 weeks, the HR was 2.12 (1.283.49) in moderate residual proteinuria and 4.59 (2.747.69) in heavy residual proteinuria. Compared with patients with residual UPCR 1.0 g/gCr and UPCR 30, the HR in those with UPCR30 and residual UPCR1.0 g/gCr was 0.38 (0.220.64). In patients with type 2 diabetes and overt nephropathy, over 30 reduction of UPCR compared with baseline and/or residual UPCR1.0 g/gCr at 24 weeks predicted renoprotection. These values may be used as targets to guide anti-proteinuric and renoprotective therapy in diabetic nephropathy. ClinicalTrials.gov NCT00141453.