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

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.