Objective: Ruboxistaurin selectively inhibits protein kinase C-beta and ameliorates kidney disease in animal models of diabetes. The purpose of this study was to evaluate the effects of ruboxistaurin on diabetic nephropathy in humans.

Research design and methods: A randomized, double-blind, placebo-controlled, multicenter, pilot study was performed to evaluate the effects of 32 mg/day ruboxistaurin for 1 year in persons (n = 123) with type 2 diabetes and persistent albuminuria (albumin-to-creatinine ratio [ACR] 200-2,000 mg/g), despite therapy with renin-angiotensin system inhibitors. The primary end point was a change in the ACR. Estimated glomerular filtration rate (eGFR) (four-component equation from the Modification of Diet in Renal Disease study) was also calculated.

Results: At baseline, urinary ACR was 764 +/- 427 mg/g (means +/- SD), and eGFR was 70 +/- 24 ml/min per 1.73 m2. Systolic and diastolic blood pressures were 135 +/- 14 and 75 +/- 9 mmHg, respectively. HbA(1c) was 8.0 +/- 1.2%. After 1 year, urinary ACR decreased significantly (-24 +/- 9%) in participants treated with ruboxistaurin (P = 0.020) and nonsignificantly (-9 +/- 11%) in the placebo group (P = 0.430). The ACR-lowering effect of ruboxistaurin appeared by 1 month. eGFR did not decline significantly in the ruboxistaurin group (-2.5 +/- 1.9 ml/min per 1.73 m2) (P = 0.185), whereas the placebo group lost significant eGFR over 1 year (-4.8 +/- 1.8 ml/min per 1.73 m2) (P = 0.009). Between-group differences for changes in ACR and eGFR were not statistically significant, but this pilot study was underpowered to determine such differences.

Conclusions: In persons with type 2 diabetes and nephropathy, treatment with ruboxistaurin reduced albuminuria and maintained eGFR over 1 year. Ruboxistaurin may add benefit to established therapies for diabetic nephropathy.